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Introduction ⬇

VA Class:AM117

AHFS Class:

Generic Name(s):

Chemical Name:

Associated Monographs

Ceftriaxone is a semisynthetic, third generation cephalosporin antibiotic.1,16,104,105,106,165,171

Uses ⬆ ⬇

[Section Outline]

Ceftriaxone is used for the treatment of bone and joint infections,1,2,3,18,30,32,120,121,124,125,127,131,132,150,425,590,591 endocarditis†,414,415,417,450,452,491 intra-abdominal infections,1,2,3,18,30,32,104,105,129,132,149,708 meningitis and other CNS infections,1,2,3,18,30,32,80,86,123,130,138,139,140,141,142,143,144,145,187,197,292,418,475,506 otitis media,1,310,311,312,313,427,428,429,535,613,614,683 respiratory tract infections,1,2,3,18,30,32,87,88,104,105,119,120,121,124,125,127,128,129,131,246,313,423,493,512,513,728 septicemia,1,2,3,18,30,32,87,104,105,120,121,124,125,131,246 skin and skin structure infections,1,2,3,18,30,32,87,89,104,105,120,121,124,128,129,131,132,425,543 and urinary tract infections1,2,3,18,30,32,82,91,104,119,120,121,124,125,127,128,129,131,246,446,743 caused by susceptible bacteria. The drug also is used for the treatment of chancroid†,210,211,229,241,274,344,345 gonorrhea and associated infections,1,2,3,18,30,32,81,90,114,115,116,117,118,292,336,344,345 pelvic inflammatory disease,1,2,3,18,30,32,292,397,398,344 infections caused by Neisseria meningitidis †,166,197,292,418,475 infections caused by Shigella †,197,217,292,401,402,403 and typhoid fever† and other infections caused by Salmonella †.167,188,197,217,267,292,403,404,405,406,407,408,409,410,440 In addition, ceftriaxone is used for the treatment of Lyme disease†197,292,329,342,357,358,359,361,362,363,364,365,366,367,492,498 and has been used for empiric anti-infective therapy in febrile neutropenic patients†387,388,437,457 and for perioperative prophylaxis.1,2,3,18,30,32,67,104,105,147,148,151,152,153,154,155,157,294,295,296,297,298,360,374

Ceftriaxone has a wide spectrum of activity and is effective for the treatment of infections caused by a variety of gram-positive and gram-negative bacteria.435 Like other parenteral third generation cephalosporins (cefotaxime, ceftazidime), ceftriaxone is less active than first and second generation cephalosporins against some gram-positive aerobic bacteria (e.g., staphylococci) and generally should not be used in the treatment of infections caused by these organisms when a penicillin or first or second generation cephalosporin could be used.89,104,105,106,110,127,160,170,175,246,250,292 However, ceftriaxone may be a drug of choice for serious infections caused by certain other gram-positive bacteria, including Streptococcus pneumoniae .197,292 Ceftriaxone is considered a drug of choice for many infections caused by gram-negative bacteria,197,435 and a principal use of the drug is for the treatment of serious gram-negative bacterial infections, especially nosocomial infections, when other anti-infectives are ineffective or contraindicated.125,435

Because ceftriaxone has a long serum half-life and can be administered once daily, the drug has been used for community-based parenteral anti-infective therapy for the treatment of infections that require prolonged therapy (e.g., community-acquired pneumonia, osteomyelitis, endocarditis†).125,126,132,150,206,246,259,380,381,414,415,417,421,422,423,424,425,426,450 Ceftriaxone has been administered parenterally to adults and children in outpatient settings, including clinicians' office, outpatient clinics, infusion centers, skilled nursing facilities, rehabilitation centers, and the patient's home.125,126,132,150,206,246,259,380,381,415,417,421,422,423,424,425,426,437 Outpatient parenteral anti-infective therapy generally is used to complete a course of ceftriaxone therapy initiated during hospitalization, but ceftriaxone therapy also has been initiated on an outpatient basis in patients who were clinically stable.125,415,423,424,425,426 When considering use of community-based ceftriaxone therapy, the benefits and risks of such therapy should be considered.415,422

Prior to initiation of ceftriaxone therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests.1,2,3,18,30,32 Ceftriaxone therapy may be started pending results of susceptibility tests, but should be discontinued if the organism is found to be resistant to the drug.1,2,3,18,30,32

Bone and Joint Infections !!navigator!!

Ceftriaxone is used in adults and pediatric patients for the treatment of bone and joint infections (e.g., osteomyelitis, septic arthritis) caused by susceptible Staphylococcus aureus , Streptococcus pneumoniae , Escherichia coli , Proteus mirabilis , Klebsiella pneumoniae , or Enterobacter .1,2,3,18,30,32,87,104,121,124,127,131,132,150,246,590,591

For the treatment of native vertebral osteomyelitis or prosthetic joint infections caused by oxacillin-susceptible staphylococci, the Infectious Diseases Society of America (IDSA) recommends IV nafcillin (or oxacillin), IV cefazolin, or IV ceftriaxone as the drugs of choice.590,591 If native vertebral osteomyelitis or prosthetic joint infections are caused by β-hemolytic streptococci†, IDSA recommends IV penicillin G or IV ceftriaxone.590,591 For the treatment of native vertebral osteomyelitis or prosthetic joint infections caused by Cutibacterium acnes † (formerly Propionibacterium acnes ), IDSA recommends IV penicillin G or IV ceftriaxone.590,591 These experts also recommend IV ceftriaxone as an alternative to ciprofloxacin for the treatment of native vertebral osteomyelitis caused by susceptible Salmonella †.590

For additional information on management of bone and joint infections, current clinical practice guidelines from IDSA available at [Web] should be consulted.590,591

Endocarditis !!navigator!!

Ceftriaxone is used for the treatment of endocarditis† caused by various streptococci, including viridans group streptococci (e.g., S. milleri group, S. mutans , S. salivarius , S. sanguis ), nonenterococcal group D streptococci (e.g., S. gallolyticus [formerly S. bovis ]), S. pneumoniae , S. pyogenes (group A β-hemolytic streptococci; GAS), S. agalactiae (group B streptococci; GBS), or streptococci groups C, F, or G.415,417,450,452,491 The drug also is used for the treatment of endocarditis† caused by enterococci (e.g., Enterococcus faecalis , E. faecium )450,452 or fastidious gram-negative bacilli of the HACEK group (i.e., Haemophilus , Aggregatibacter , Cardiobacterium hominis , Eikenella corrodens , Kingella ).450,452 Ceftriaxone has been administered on an outpatient basis for the treatment of endocarditis† caused by susceptible bacteria.414,415,450,452

Ceftriaxone also is used for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk of adverse outcomes from endocarditis.451 (See Uses: Prevention of Bacterial Endocarditis.)

The American Heart Association (AHA) recommends that treatment of endocarditis be managed in consultation with an infectious disease expert, especially when endocarditis is caused by S. pneumoniae , β-hemolytic streptococci, staphylococci, or enterococci.450,452

For additional information on management of endocarditis, current guidelines from AHA should be consulted.450,452

Endocarditis Caused by Viridans Group Streptococci or S. gallolyticus

For the treatment of native valve endocarditis† caused by viridans group streptococci or S. gallolyticus (formerly S. bovis ) highly susceptible to penicillin (penicillin MIC 0.12 mcg/mL or less), AHA states that a 4-week regimen of IV penicillin G or IV or IM ceftriaxone is reasonable in adults and pediatric patients.450,452 If necessary in those unable to tolerate penicillin G or ceftriaxone, a 4-week regimen of IV vancomycin can be used.450,452 In selected adults, AHA states that a 2-week regimen that consists of IV penicillin G or IV or IM ceftriaxone in conjunction with IV or IM gentamicin is reasonable.450 The 2-week regimen should be considered only in adults with uncomplicated native valve endocarditis caused by highly penicillin-susceptible viridans group streptococci or S. gallolyticus who are at low risk for gentamicin adverse effects; the 2-week regimen is not recommended in those with known cardiac or extracardiac abscess, creatinine clearance less than 20 mL/minute, impaired eighth cranial nerve function, or infections caused by Abiotrophia , Granulicatella , or Gemella .450 In addition, AHA states that the 2-week regimen is not recommended in pediatric patients because of lack of clinical data.452

For the treatment of native valve endocarditis† caused by viridans group streptococci or S. gallolyticus relatively resistant to penicillin (penicillin MIC greater than 0.12 mcg/mL but less than 0.5 mcg/mL), AHA states that a 4-week regimen of either IV penicillin G (or IV ampicillin) or IV or IM ceftriaxone in conjunction with IV or IM gentamicin given during the initial 2 weeks of treatment is reasonable in adults and pediatric patients.450,452 If the isolate is susceptible to ceftriaxone, AHA states that a 4-week regimen of ceftriaxone alone may be considered in adults.450 A 4-week regimen of vancomycin alone is a reasonable alternative only in adults unable to tolerate β-lactam anti-infectives.450

If native valve endocarditis is caused by viridans group streptococci, Abiotrophia defectiva , or Granulicatella that are resistant to penicillin (penicillin MIC 0.5 mcg/mL or greater), AHA states that a regimen of IV penicillin G (or ampicillin) in conjunction with gentamicin is reasonable in adults.450 These experts state that a regimen of ceftriaxone in conjunction with gentamicin may be a reasonable alternative in adults for the treatment of native valve endocarditis† caused by viridans group streptococci that are resistant to penicillin but susceptible to ceftriaxone.450

For the treatment of endocarditis† involving prosthetic valves or other prosthetic material caused by viridans group streptococci or S. gallolyticus highly susceptible to penicillin (penicillin MIC 0.12 mcg/mL or less), AHA states that a 6-week regimen of IV penicillin G or IV or IM ceftriaxone given with or without IV or IM gentamicin during the initial 2 weeks of treatment is reasonable in adults.450 When highly penicillin-susceptible strains are involved, there is no evidence that use of the combination regimen that includes gentamicin during the first 2 weeks is more effective than use of the β-lactam alone.450 If endocarditis† involving prosthetic valves or other prosthetic material is caused by viridans group streptococci or S. gallolyticus relatively or highly resistant to penicillin (penicillin MIC greater than 0.12 mcg/mL), AHA states that it is reasonable for adults to receive a 6-week regimen of IV penicillin G or IV or IM ceftriaxone given with a 6-week regimen of IV or IM gentamicin.450 In adults unable to tolerate penicillin G, ceftriaxone, or gentamicin, a 6-week regimen of IV vancomycin can be used.450

Endocarditis Caused by S. pneumoniae, S. pyogenes, S. agalactiae, or Groups C, F, and G Streptococci

For the treatment of endocarditis† involving native valves or prosthetic valves or other prosthetic material caused by S. pneumoniae highly susceptible to penicillin (penicillin MIC 0.1 mcg/mL or less), AHA states that penicillin G, ceftriaxone, or cefazolin are reasonable choices in adults.450 If endocarditis is caused by S. pneumoniae with penicillin resistance (penicillin MIC greater than 0.1 mcg/mL), AHA states that treatment with high-dose penicillin G or a third generation cephalosporin (cefotaxime, ceftriaxone) is reasonable in adults if meningitis is not present; cefotaxime or ceftriaxone is reasonable if meningitis is present.450 AHA states that use of cefotaxime or ceftriaxone in conjunction with vancomycin and rifampin may be considered in adults if endocarditis is caused by S. pneumoniae resistant to cefotaxime (cefotaxime MIC greater than 2 mcg/mL).450

For the treatment of endocarditis† caused by S. pyogenes , AHA states that penicillin G is a reasonable regimen in adults and ceftriaxone is a reasonable alternative.450 Vancomycin is a reasonable alternative only for those unable to tolerate β-lactam anti-infectives.450

AHA states that penicillin G or ceftriaxone is a reasonable regimen for the treatment of endocarditis† caused by S. agalactiae or groups C and G streptococci in adults, but concomitant use of gentamicin during the initial weeks of treatment should be considered.450

Enterococcal Endocarditis

For the treatment of enterococcal endocarditis†, AHA states that a double-β-lactam regimen of ampicillin and ceftriaxone is a reasonable option in certain adults.450

Enterococcus (e.g., E. faecalis , E. faecium ) are relatively resistant to penicillins and vancomycin and a synergistic combination regimen of penicillin, ampicillin, or vancomycin in conjunction with an aminoglycoside (gentamicin or streptomycin) has usually been used for the treatment of enterococcal endocarditis.450 However, enterococci resistant to aminoglycosides have been reported with increasing frequency and AHA states that all enterococcal isolates should be routinely tested for in vitro susceptibility to penicillin and vancomycin and for high-level resistance to gentamicin to predict synergistic interactions and aid in selection of the most appropriate treatment regimen.450

Although there are few therapeutic alternatives to aminoglycoside-containing regimens for the treatment of enterococcal endocarditis, there are some data from in vitro and in vivo studies and limited clinical experience indicating that a double β-lactam regimen of ampicillin and ceftriaxone can be effective for the treatment of endocarditis caused by E. faecalis , including gentamicin-resistant strains.450 The major advantages of the ampicillin and ceftriaxone regimen are the lower risk of nephrotoxicity and the lack of any need to measure aminoglycoside serum concentrations; a potential disadvantage of this regimen is the possibility of hypersensitivity reactions to 2 separate β-lactam anti-infectives.450

For the treatment of enterococcal endocarditis† involving native valves, prosthetic valves, or other prosthetic material caused by strains susceptible to penicillin and gentamicin in adults who can tolerate β-lactam anti-infectives, AHA states that either a regimen of IV ampicillin or IV penicillin G given in conjunction with gentamicin for 4-6 weeks or a double β-lactam regimen of IV ampicillin and IV ceftriaxone given for 6 weeks is reasonable.450 The most appropriate regimen should be selected based on characteristics of the individual patient.450 The double β-lactam regimen is recommended in adults who should not receive an aminoglycoside (i.e., creatinine clearance less than 50 mL/minute [pretreatment or developed during treatment with a gentamicin-containing regimen], impaired eighth cranial nerve function).450

For the treatment of enterococcal endocarditis† involving native valves, prosthetic valves, or other prosthetic material caused by strains susceptible to penicillin but resistant to gentamicin in adults who can tolerate β-lactam anti-infectives, AHA states that a double β-lactam regimen of IV ampicillin and IV ceftriaxone given for 6 weeks is reasonable.450 If enterococcal endocarditis is caused by penicillin-susceptible strains that are gentamicin-resistant but streptomycin-susceptible, a double β-lactam regimen of IV ampicillin and IV ceftriaxone given for 6 weeks is reasonable in adults; alternatively, a regimen of IV ampicillin or IV penicillin G given in conjunction with IV or IM streptomycin for 4-6 weeks can be considered if the patient has a creatinine clearance of 50 mL/minute or greater and rapid tests for streptomycin serum concentrations are available.450 A 6-week regimen of vancomycin in conjunction with gentamicin should be considered only when enterococcal endocarditis is caused by strains intrinsically resistant to penicillin or the patient cannot tolerate β-lactam anti-infectives.450

Endocarditis Caused by the HACEK Group

AHA states that ceftriaxone is a reasonable option for the treatment of endocarditis† caused by the HACEK group in adults and pediatric patients.450,452

The slow-growing fastidious gram-negative bacilli known as the HACEK group (i.e., Haemophilus , Aggregatibacter , C. hominis , E. corrodens , Kingella ) account for approximately 5-10% of cases of community-acquired native valve endocarditis in patients who are not IV drug abusers and also rarely cause prosthetic valve endocarditis.438,439,450 Because β-lactamase-producing strains have been reported with increasing frequency, AHA states that the HACEK group should be considered ampicillin-resistant and penicillin and ampicillin should not be used for the treatment of HACEK endocarditis unless results of in vitro susceptibility testing are available.450

AHA states that a 4-week regimen of IV or IM ceftriaxone alone is a reasonable choice for the treatment of native valve endocarditis† caused by the HACEK group and a 6-week regimen of the drug is a reasonable choice for the treatment of endocarditis involving prosthetic valves or other prosthetic material† caused by the HACEK group since most strains are susceptible to ceftriaxone or other third or fourth generation cephalosporins.450 Although ceftriaxone is preferred in such patients, cefotaxime or another third or fourth generation cephalosporin could be substituted and IV ampicillin is an option if in vitro susceptibility testing is performed and the isolate is susceptible.450 For the treatment of HACEK endocarditis in adults unable to tolerate ceftriaxone or other appropriate cephalosporin, AHA states that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered as an alternative since the HACEK group usually is susceptible to fluoroquinolones in vitro; however, such patients should be treated in consultation with an infectious disease specialist.450

In pediatric patients with endocarditis caused by the HACEK group, AHA recommends a 4-week regimen of ceftriaxone or another third-generation cephalosporin (e.g., cefotaxime) used alone or a regimen of ampicillin in conjunction with gentamicin (or amikacin or tobramycin).452

GI Infections !!navigator!!

Ceftriaxone has been used for the treatment of gastroenteritis† caused by Salmonella 292,299,440 or Shigella .401,402 Ceftriaxone also is recommended as an alternative for empiric treatment of infectious diarrhea† in individuals with human immunodeficiency virus (HIV) infection or for long-term suppressive antibacterial therapy† (secondary prophylaxis) in such individuals.440

Salmonella Gastroenteritis

Anti-infective therapy generally is not indicated in otherwise healthy individuals with uncomplicated (noninvasive) gastroenteritis caused by nontyphoidal Salmonella (e.g., Salmonella serovars Enteritidis or Typhimurium) since such therapy may prolong the duration of fecal excretion of the organism and there is no evidence that it shortens the duration of the disease; however, the US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), IDSA, and others recommend anti-infective therapy in individuals with severe Salmonella gastroenteritis and in those who are at increased risk for invasive disease.217,292,299,440 These individuals include infants younger than 3-6 months of a individuals older than 50 years of a individuals with hemoglobinopathies, severe atherosclerosis or valvular heart disease, prostheses, uremia, chronic GI disease, or severe colitis; and individuals who are immunocompromised because of malignancy, immunosuppressive therapy, HIV infection, or other immunosuppressive illness.217,292,440

When an anti-infective agent is considered necessary in an individual with Salmonella gastroenteritis, CDC, AAP, IDSA, and others recommend ceftriaxone, cefotaxime, a fluoroquinolone (should be used in children only if benefits outweigh risks and no other alternative exists), ampicillin, amoxicillin, co-trimoxazole, or chloramphenicol, depending on susceptibility of the causative organism.197,217,292,299,440 Some experts recommend that patients with presumed or proven nontyphoidal Salmonella gastroenteritis receive an initial dose of ceftriaxone followed by oral azithromycin pending results of diagnostic evaluation.292 The fact that multidrug-resistant Salmonella have been reported with increasing frequency in the US should be considered.352

Because HIV-infected individuals with Salmonella infections are at increased risk for bacteremia and mortality compared with patients without HIV infection, CDC, NIH, and IDSA recommend that all HIV-infected patients with salmonellosis receive antibacterial treatment.440 In addition, some clinicians suggest that long-term suppressive antibacterial therapy (secondary prophylaxis) can be considered in HIV-infected adults and adolescents with recurrent Salmonella gastroenteritis (with or without bacteremia) and in those with CD4+ T-cell counts less than 200 cells/mm3 and severe diarrhea.440 However, the value of secondary prophylaxis has not been established and possible benefits must be weighed against the risks of long-term antibacterial exposure.440 CDC, NIH, and IDSA state that ciprofloxacin is the drug of choice for the treatment of Salmonella gastroenteritis (with or without bacteremia) and for long-term suppressive therapy in HIV-infected adults and adolescents; other fluoroquinolones (e.g., levofloxacin, moxifloxacin) are likely to be effective, but clinical data are limited.440 Depending on in vitro susceptibility of the causative organism, these experts recommend co-trimoxazole, ceftriaxone, or cefotaxime as alternatives for such treatment or secondary prophylaxis in HIV-infected adults and adolescents.440

For information on the treatment of typhoid and paratyphoid fever (enteric fever) or bacteremia caused by Salmonella , see Uses: Typhoid Fever and Other Invasive Salmonella Infections.

Shigella Infections

Ceftriaxone has been effective when used for the treatment of shigellosis† caused by susceptible Shigella sonnei or S. flexneri 401,402 and has been recommended as an alternative when anti-infectives are indicated for the treatment of shigella infections.197,292

Infections caused by S. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives.292 However, since anti-infectives may shorten the duration of diarrhea and period of fecal excretion of Shigella , anti-infective treatment generally is recommended in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression.292,440

Although an empiric regimen can be used initially when anti-infectives are indicated in the treatment of Shigella infections,292 in vitro susceptibility testing of clinical isolates is indicated since resistance to ampicillin and co-trimoxazole is common and strains resistant to ciprofloxacin, ceftriaxone, or azithromycin have been reported with increasing frequency.292,440 For infections caused by Shigella resistant to ampicillin and co-trimoxazole or when in vitro susceptibility of the isolate is unknown, ceftriaxone, a fluoroquinolone (e.g., ciprofloxacin), or azithromycin is recommended.217,292,403

For the treatment of Shigella infections in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the drug of choice is ciprofloxacin and alternatives are levofloxacin, moxifloxacin, co-trimoxazole, or azithromycin.440

Empiric Treatment of Infectious Diarrhea

CDC, NIH, and IDSA recommend that adults and adolescents with advanced HIV disease (CD4+ T-cell counts less than 200 cells/mm3 or concomitant AIDS-defining illness) who have clinically severe diarrhea (i.e., 6 or more liquid stools per day, bloody stools, or any number of liquid stools per day accompanied by fever or chills) should undergo diagnostic evaluation to determine the etiology of the diarrheal illness and receive appropriate anti-infective treatment.440 These experts state that ciprofloxacin is preferred and ceftriaxone and cefotaxime are reasonable alternatives when empiric treatment of severe bacterial diarrhea is indicated in HIV-infected adults and adolescents.440 Treatment should be adjusted if needed when results of diagnostic testing are available.440 If diarrhea persists for longer than 14 days without other clinical signs of severity (e.g., bloody stool, dehydration), additional evaluation is indicated and pathogen-directed therapy should be initiated after a diagnosis is confirmed.440

The possibility of resistant infections should be considered when selecting an empiric anti-infective regimen for treatment of diarrhea in HIV-infected travelers during travel or after return to the US.440

Intra-abdominal Infections !!navigator!!

Ceftriaxone is used for the treatment of intra-abdominal infections caused by susceptible E. coli , K. pneumoniae , Clostridium , or Peptostreptococcus .1,2,3,18,30,32,104,105,129,132,149 The drug also has been used for the treatment of various gynecologic infections, including pelvic inflammatory disease.1,2,3,18,30,32,125,292,344,397,398,459,460 (See Uses: Pelvic Inflammatory Disease.) Although the manufacturers state that ceftriaxone can be used for the treatment of intra-abdominal infections caused by Bacteroides fragilis ,1,2,3,18,30,32 the drug has been ineffective in the treatment of intra-abdominal infections when B. fragilis was present and superinfection with this organism has been reported occasionally.119,121,128,132,250

Although monotherapy with ceftriaxone is an option for initial empiric treatment of mild to moderate community-acquired biliary tract infections (acute cholecystitis or cholangitis), ceftriaxone should be used in conjunction with metronidazole for initial empiric treatment of mild to moderate extrabiliary community-acquired intra-abdominal infections.708

For additional information on management of intra-abdominal infections, current clinical practice guidelines from IDSA available at [Web] should be consulted.708

Meningitis and Other CNS Infections !!navigator!!

Ceftriaxone is used in neonates,104,140,142,144,243,249,250,292 children,80,87,104,130,139,140,141,142,143,144,187,243,245,246,249,250,257,258,259,270,272,292,418 and adults80,87,104,138,270,271,418 for the treatment of meningitis caused by susceptible H. influenzae , N. meningitidis , or S. pneumoniae .1,2,3,18,30,32 The drug also has been used for the treatment of meningitis and other CNS infections caused by susceptible Enterobacteriaceae† (e.g., E. coli , Klebsiella †)1,2,18,30,32,104,133,156 or S. epidermidis .1,2,3,18,30,32

IV cefotaxime with or without other anti-infectives (e.g., ampicillin, gentamicin, vancomycin) has been recommended for empiric treatment of meningitis†.292,343,418,419,468,471,475 Pending results of CSF culture and in vitro susceptibility testing, the most appropriate anti-infective regimen for empiric treatment of suspected bacterial meningitis should be selected based on results of CSF gram stain and antigen tests, age of the patient, the most likely pathogen(s) and source of infection, and current patterns of bacterial resistance within the hospital and local community.243,292,418,419,471,475 When results of culture and susceptibility tests become available and the pathogen is identified, the empiric anti-infective regimen should be modified (if necessary) to ensure that the most effective regimen is being administered.243,292,418,419,475 Ceftriaxone should not be used alone for empiric treatment of meningitis when Listeria monocytogenes , enterococci, staphylococci, or Pseudomonas aeruginosa may be involved.9,87,137,292,468,475

Meningitis Caused by Streptococcus pneumoniae

IV ceftriaxone and IV cefotaxime are considered drugs of choice for the treatment of meningitis caused by susceptible S. pneumoniae .197,243,292,418,475 While cefotaxime and ceftriaxone generally have been considered the drugs of choice when meningitis is caused by penicillin-resistant S. pneumoniae , treatment failures have been reported when these cephalosporins were used alone for the treatment of meningitis caused by S. pneumoniae with intermediate or high-level penicillin resistance (i.e., penicillin MIC 0.1 mcg/mL or greater).292,324,331,332,334,346,347,349,434 In addition, strains of S. pneumoniae with reduced susceptibility to cephalosporins have been reported with increasing frequency and use of cefotaxime or ceftriaxone alone may be ineffective for the treatment of meningitis caused by these strains.109,111,470,471 The prevalence of S. pneumoniae with reduced susceptibility to penicillin and/or cephalosporins varies geographically, and clinicians should be aware of the prevalence and pattern of S. pneumoniae drug resistance in the local community to optimize empiric and initial treatment regimens for serious pneumococcal infections.111,242,292,323,333 Because susceptibility can no longer be assumed, S. pneumoniae isolates should be routinely tested for in vitro susceptibility.243,292,323,330,324,419

If anti-infective therapy in a patient with meningitis is initiated with an empiric regimen of IV ceftriaxone and IV vancomycin (with or without rifampin) and results of culture and in vitro susceptibility testing indicate that the pathogen involved is a strain of S. pneumoniae susceptible to ceftriaxone and susceptible or resistant to penicillin, vancomycin and rifampin can be discontinued and therapy completed using ceftriaxone alone.292,475 If the isolate is found to have reduced susceptibility to ceftriaxone and penicillin, both IV ceftriaxone and IV vancomycin usually are continued and consideration given to adding rifampin to the regimen.292,418,475 If meningitis is caused by S. pneumoniae highly resistant to ceftriaxone (i.e., MIC 4 mcg/mL or greater), consultation with an infectious disease expert is recommended.292

Meningitis Caused by Haemophilus influenzae

IV ceftriaxone and IV cefotaxime are considered drugs of choice for initial treatment of meningitis caused by susceptible H. influenzae (including penicillinase-producing strains).105,141,197,292,418,419,475 In children, AAP suggests that ampicillin may be substituted if the isolate is susceptible; however, because of the prevalence of ampicillin-resistant H. influenzae , ampicillin should not be used alone for empiric treatment of meningitis when H. influenzae may be involved.292 The incidence of H. influenzae meningitis in the US has decreased considerably since H. influenzae type b (Hib) conjugate vaccines became available for immunization of infants.292,468,471

Meningitis Caused by Neisseria meningitidis

IV ceftriaxone and IV cefotaxime are considered drugs of choice for empiric treatment of meningitis when N. meningitidis may be involved.166,292,475 If a diagnosis of N. meningitidis meningitis is confirmed, AAP and other clinicians suggest treatment with penicillin G or, alternatively, ampicillin, ceftriaxone, or cefotaxime.166,197,292,418,475 Chloramphenicol, if available, is recommended by AAP for the treatment of N. meningitidis meningitis in patients with a history of anaphylactoid-type hypersensitivity reactions to penicillin. 292

Meningitis Caused by Enterobacteriaceae

Some clinicians recommend that meningitis caused by Enterobacteriaceae† (e.g., E. coli , K. pneumoniae †) be treated with a third generation cephalosporins (i.e., cefotaxime, ceftazidime, ceftriaxone) with or without an aminoglycoside.418,419,475 Because ceftazidime (but not cefotaxime or ceftriaxone) is effective for the treatment of meningitis caused by Ps. aeruginosa , some clinicians suggest that a regimen of ceftazidime and an aminoglycoside may be preferred for the treatment of meningitis caused by gram-negative bacilli pending results of culture and in vitro susceptibility testing.475

Meningitis Caused by Streptococcus agalactiae

Third generation cephalosporins (i.e., ceftriaxone, cefotaxime) have been suggested as an alternative for the treatment of meningitis caused by S. agalactiae †.418

For initial treatment of meningitis or other severe infection caused by S. agalactiae , a regimen of IV ampicillin or IV penicillin G given in conjunction with an aminoglycoside is recommended.292,418,475 Some clinicians suggest that IV ampicillin is the drug of choice for the treatment of S. agalactiae meningitis and that an aminoglycoside (IV gentamicin) should be used concomitantly during the first 72 hours until in vitro susceptibility testing is completed and a clinical response is observed; thereafter, ampicillin can be given alone if the strain is susceptible to the drug.475

Meningitis Caused by Listeria monocytogenes

The optimal regimen for the treatment of meningitis caused by L. monocytogenes has not been established.292 Ceftriaxone is ineffective in and should not be used alone for the treatment of meningitis caused by L. monocytogenes .87,137,197,292,468,475 AAP and other clinicians generally recommend that meningitis or other severe infection caused by L. monocytogenes be treated with a regimen of IV ampicillin with or without an aminoglycoside (usually gentamicin);197,292,418,475,479 alternatively, a regimen of penicillin G in conjunction with gentamicin can be used.418,475,479 In patients hypersensitive to penicillin, the preferred alternative regimen for treatment of meningitis caused by L. monocytogenes is co-trimoxazole.197,292

Other CNS Infections

Ceftriaxone is a drug of choice for the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible β-lactamase-producing H. influenzae or susceptible Enterobacteriaceae†.416 Ceftriaxone also is a drug of choice for the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible S. pneumoniae when penicillin G is not the preferred anti-infective (i.e., penicillin MIC 0.12 mcg/mL or greater).416 Some experts state that ceftriaxone can be used alone if the infection is caused by S. pneumoniae with penicillin MIC less than 1 mcg/mL, but should be used in conjunction with vancomycin if the strain has a penicillin MIC 1 mcg/mL or greater and that consideration should be given to also including rifampin in the regimen if the strain has a ceftriaxone MIC greater than 2 mcg/mL.416

Although penicillin G usually is the drug of choice, ceftriaxone is recommended as an alternative for the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible C. acnes † (formerly P. acnes ).416

Acute Otitis Media !!navigator!!

IM ceftriaxone is used for the treatment of acute otitis media (AOM) caused by S. pneumoniae , H. influenzae (including β- lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).1,2,310,311,312,313,427,428,429,458,614,683

When anti-infective therapy is indicated for the treatment of AOM, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate potassium as the drug of first choice for initial treatment.683 These experts recommend certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients who do not have a history of severe and/or recent penicillin-allergic reactions.683

Ceftriaxone has been shown to be effective for initial or repeat treatment of AOM, and is a good choice when the patient has persistent vomiting or cannot otherwise tolerate an oral regimen.683 The manufacturers recommend a single-dose regimen of IM ceftriaxone for the treatment of AOM, but caution that the potential advantages of this single-dose parenteral regimen should be balanced against its potentially lower clinical cure rate compared with a 10-day oral anti-infective regimen.1,2 AAP states that either a 1- or 3-day regimen† of IM or IV ceftriaxone can be used for initial treatment of AOM, but cautions that there is some evidence that more than a single dose of the drug may be required to prevent recurrence of middle ear infections within 5-7 days after the initial dose.683 A 3-day regimen† of ceftriaxone is recommended for retreatment in patients who fail to respond to initial treatment with other anti-infectives.535,613,683

Results of several controlled clinical studies in pediatric patients with AOM indicate that the short-term clinical response rate to a single-dose IM ceftriaxone regimen is similar to that of a 10-day regimen of oral cefaclor (40 mg/kg daily),427 a 7- or 10-day regimen of oral amoxicillin (40 mg/kg daily),311,312 a 10-day regimen of oral co-trimoxazole (8 mg/kg trimethoprim and 40 mg/kg of sulfamethoxazole daily),310 or a 10-day regimen of oral amoxicillin and clavulanate potassium;458,614 however, in one study, the single-dose IM ceftriaxone regimen had a lower clinical cure rate than a 10-day regimen of oral amoxicillin and clavulanate potassium.1,2

A 3-day regimen of IM ceftriaxone has been shown to be more effective than a 1-day regimen for retreatment in patients who fail to respond to initial treatment with another anti-infective.683 The 3-day ceftriaxone regimen has been effective for the treatment of persistent or relapsing otitis media caused by H. influenzae , M. catarrhalis , S. pyogenes , or penicillin-susceptible S. pneumoniae ; however, treatment failures have been reported when the causative agent was S. pneumoniae with reduced susceptibility to penicillin.535,613

For additional information on diagnosis and management of AOM, current AAP clinical practice guidelines for AOM should be consulted.683

Respiratory Tract Infections !!navigator!!

Ceftriaxone is used in adults and pediatric patients for the treatment of lower respiratory tract infections (including pneumonia) caused by susceptible gram-positive cocci (e.g., S. pneumoniae , S. aureus ) or gram-negative bacteria (e.g., H. influenzae , H. parainfluenzae , K. pneumoniae , E. coli , Enterobacter aerogenes , P. mirabilis , Serratia marcescens ).1,2,3,18,30,32,87,88,104,105,119,120,121,124,125,127,128,129,131,246,313,390,423,448,456,493,512,513,728 Ceftriaxone generally has been effective in the treatment of pneumonia caused by S. pneumoniae with intermediate resistance to penicillin (i.e., penicillin MIC less than 0.1-2 mcg/mL), but treatment failures have been reported when the drug was used alone in the treatment of severe infections (e.g., meningitis) caused by strains with intermediate or high-level penicillin resistance (i.e., penicillin MIC 0.12 mcg/mL or greater).292,324,331,332,334,346,347,349,434 (See Uses: Meningitis and Other CNS Infections.)

Acute Sinusitis

Ceftriaxone is used as an alternative for the treatment of acute bacterial sinusitis†.728,729

When anti-infective therapy is indicated for the treatment of acute bacterial sinusitis, IDSA recommends amoxicillin and clavulanate potassium and AAP recommends either amoxicillin or amoxicillin and clavulanate potassium as the drug of choice for initial empiric treatment.728,729 Because of variable activity against S. pneumoniae and H. influenzae , IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of sinusitis in adults or children.728 If an oral cephalosporin is used as an alternative for empiric treatment of acute bacterial sinusitis in children (e.g., in penicillin-allergic individuals), IDSA and AAP recommend a combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid).728,729 In children who are vomiting, unable to tolerate oral therapy, or unlikely to adhere to the initial doses, treatment of acute sinusitis can be initiated with a single dose of IV or IM ceftriaxone and then switched to an oral regimen if clinical improvement is observed at 24 hours.728,729 IV ceftriaxone also is an alternative for severe sinusitis requiring hospitalization.728,729

Community-acquired Pneumonia

IDSA and the American Thoracic Society (ATS) recommend ceftriaxone as an alternative to penicillin G, ampicillin, or amoxicillin for the treatment of community-acquired pneumonia (CAP) caused by penicillin-susceptible S. pneumoniae and as a preferred drug for the treatment of CAP caused by penicillin-resistant S. pneumoniae , provided in vitro susceptibility has been demonstrated.512,513 These experts state that ceftriaxone is a preferred anti-infective for the treatment of CAP caused by β-lactamase-producing H. influenzae .513 IDSA and ATS also recommend use of ceftriaxone in certain combination regimens used for empiric treatment of CAP.512,513 The drug has been administered on an outpatient basis for empiric anti-infective therapy in adults with CAP who did not require hospitalization.456,512

Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns; therapy may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing.512 The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation and whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., penicillin- or multidrug-resistant S. pneumoniae , enteric gram-negative bacilli, Ps. aeruginosa ).512

Most experts recommend that an empiric regimen for treatment of CAP include an anti-infective active against S. pneumoniae since this organism is the most commonly identified cause of bacterial pneumonia and causes more severe disease than many other common CAP pathogens.227,512 Pathogens most frequently involved in outpatient CAP include S. pneumoniae , M. pneumoniae , Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ), respiratory viruses, and H. influenzae .512 Pathogens most frequently involved in inpatient CAP in non-ICU patients are S. pneumoniae , M. pneumoniae , C. pneumoniae , H. influenzae , Legionella , and respiratory viruses.512 Patients with severe CAP admitted into the ICU usually have infections caused by S. pneumoniae , S. aureus , Legionella , gram-negative bacilli, or H. influenzae .512 Coverage against anaerobic bacteria usually is indicated only in classic aspiration pleuropulmonary syndrome in patients who had loss of consciousness as a result of alcohol or drug overdosage or after seizures in patients with concomitant gingival disease or esophageal motility disorders.512

Inpatient treatment of CAP is initiated with a parenteral regimen, although therapy may be changed to an oral regimen if the patient is improving clinically, is hemodynamically stable, able to ingest drugs, and has a normally functioning GI tract.512 CAP patients usually have a clinical response within 3-7 days after initiation of therapy and a switch to oral therapy generally can be made during this period.512

For empiric outpatient treatment of CAP in adults when risk factors for drug-resistant S. pneumoniae are present (e.g., comorbidities such as chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancies, asplenia, immunosuppression, use of anti-infectives within the last 3 months), ATS and IDSA recommend monotherapy with a fluoroquinolone active against S. pneumoniae (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.512

For empiric inpatient treatment of CAP in adult non-ICU patients, IDSA and ATS recommend monotherapy with a fluoroquinolone (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin).512 For empiric inpatient treatment of CAP in adult ICU patients when Pseudomonas and methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).512

For additional information on management of respiratory tract infections, including CAP, current clinical practice guidelines from IDSA available at [Web] should be consulted.512,513,728

Septicemia !!navigator!!

Ceftriaxone is used in adults and pediatric patients for the treatment of septicemia caused by S. aureus , S. pneumoniae , H. influenzae , E. coli , or K. pneumoniae .1,2,3,18,30,32,87,104,105,120,121,124,125,131,246

Skin and Skin Structure Infections !!navigator!!

Ceftriaxone is used for the treatment of skin and skin structure infections caused by susceptible S. aureus , S. epidermidis , S. pyogenes , viridans group streptococci, E. cloacae , E. coli , K. oxytoca , K. pneumoniae , P. mirabilis , Morganella morganii , S. marcescens , Acinetobacter calcoaceticus , B. fragilis , or Peptostreptococcus .1,2,3,18,30,32,87,89,104,105,120,121,124,128,129,131,132

Ceftriaxone has been recommended for use in multiple-drug anti-infective regimens for empiric treatment of necrotizing infections of the skin, fascia, and muscle†.543 Because necrotizing fasciitis (including Fornier gangrene) may be polymicrobial (e.g., mixed aerobic-anaerobic infections) or monomicrobial (e.g., S. pyogenes , S. aureus , Vibrio vulnificus , Aeromonas hydrophila , Peptostreptococcus ), IDSA recommends that empiric anti-infective regimens be selected to provide broad-spectrum coverage.543

Ceftriaxone in conjunction with metronidazole has been recommended as an option for the treatment of surgical site infections that occur following GI or genitourinary surgery.543 For the treatment of surgical site infections that occur following procedures involving the axilla or perineum, ceftriaxone is recommended as an option;543 concomitant vancomycin may also be needed for coverage against methicillin-resistant S. aureus .543

Ceftriaxone also is one of several options recommended for empiric treatment of infected animal bite wounds543 or for empiric treatment of moderate or severe diabetic foot infections.544

Although the manufacturers state that ceftriaxone can be used for the treatment of skin and skin structure infections caused by Ps. aeruginosa ,1,2,3,18,30,32 treatment failures have been reported when ceftriaxone was used alone in the treatment of urinary tract infections or respiratory tract infections caused by Ps. aeruginosa .104,124 Some of these failures occurred because superinfection with resistant strains of Ps. aeruginosa occurred during treatment with the drug.124 Because many strains of Ps. aeruginosa are only susceptible to high concentrations of ceftriaxone in vitro and because resistant strains of the organism have developed during treatment with the drug,120,121,124,127,132,150 many clinicians state that ceftriaxone should not be used alone in any infection where Ps. aeruginosa may be present.104,105,106,124,125,128,170,250

For additional information on management of skin and skin structure infections, current clinical practice guidelines from IDSA available at [Web] should be consulted.543,544

Urinary Tract Infections !!navigator!!

Ceftriaxone is used in adult and pediatric patients for the treatment of complicated and uncomplicated urinary tract infections caused by E. coli , K. pneumoniae , M. morganii , P. mirabilis , or P. vulgaris .1,2,3,18,30,32,82,91,104,119,120,121,124,125,127,128,129,131,246,455,743

The most appropriate anti-infective for the treatment of urinary tract infections should be selected based on the severity of the infection and results of culture and in vitro susceptibility testing.446 It has been suggested that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) may be drugs of choice for the treatment of complicated urinary tract infections caused by susceptible Enterobacteriaceae, including susceptible strains of E. coli , K. pneumoniae , P. rettgeri , M. morganii , P. vulgaris , or P. stuartii ; an aminoglycoside usually is used concomitantly in severe infections.197 Ceftriaxone may be particularly useful as initial therapy for the treatment of nosocomial urinary tract infections known or suspected to be caused by multidrug-resistant Enterobacteriaceae.104,128,169,170,175 However, ceftriaxone, like other third generation cephalosporins, generally should not be used in the treatment of uncomplicated urinary tract infections when other anti-infectives with a narrower spectrum of activity could be used.105,106,128,179,446

Chancroid !!navigator!!

A single IM dose of ceftriaxone is used for the treatment of chancroid† (genital ulcers caused by H. ducreyi ).210,211,229,241,274,344,345

CDC and other clinicians state that a single IM dose of ceftriaxone, a single oral dose of azithromycin, a 3-day oral ciprofloxacin regimen (contraindicated in pregnant or lactating women), or a 7-day oral erythromycin regimen are recommended for the treatment of chancroid.344,345

HIV-infected individuals and patients who are uncircumcised may not respond to treatment of chancroid as well as those who are HIV-negative or circumcised.202,241,344,345 Clinicians should consider that, although treatment failures can occur with any of the recommended regimens, only limited data are available regarding efficacy of the single-dose ceftriaxone and single-dose azithromycin regimens for the treatment of chancroid in HIV-infected individuals.344 Because treatment failures and slow healing of ulcers are more likely in HIV-infected individuals,344 such patients should be monitored closely and more prolonged treatment or retreatment may be necessary.344,345

Data are limited regarding the prevalence of H. ducreyi resistant to the anti-infectives recommended for treatment.344 Some treatment failures that have occurred in HIV-infected individuals who received the single-dose ceftriaxone regimen for the treatment of chancroid did not appear to be related to ceftriaxone resistance since isolates of H. ducreyi obtained from these individuals were susceptible to ceftriaxone in vitro.202,241

For additional information on management of chancroid, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Gonorrhea and Associated Infections !!navigator!!

Ceftriaxone is used in adults, adolescents, and pediatric patients for the treatment of uncomplicated gonorrhea, disseminated gonorrhea (including meningitis and endocarditis), and various other gonococcal infections caused by Neisseria gonorrhoeae , including infections caused by penicillin-, fluoroquinolone-, and tetracycline-resistant strains.1,2,3,18,30,32,81,90,114,115,116,117,118,221,225,292,336,344,345 Ceftriaxone in conjunction with azithromycin is the regimen of choice for the treatment of gonococcal infections in most patients.292,344 Unlike the majority of other drugs that have been used for the treatment of gonococcal infections, ceftriaxone usually is effective for the treatment of gonorrhea at all sites, including cervical, urethral, rectal, and pharyngeal gonococcal infections.344

Recommendations for the treatment of gonorrhea have changed multiple times over the last several decades because of the ability of N. gonorrhoeae to develop resistance to anti-infectives.269,277,344,716,722 Ceftriaxone has been considered a drug of choice for the treatment of uncomplicated and disseminated gonococcal infections since 1989 when CDC first altered their guidelines to no longer recommend use of penicillins or tetracyclines for these infections because of the widespread prevalence of antibiotic-resistant N. gonorrhoeae , including penicillinase-producing N. gonorrhoeae resistant to penicillins (PPNG), strains with plasmid-mediated resistance to tetracyclines (TRNG), and strains with chromosomally mediated resistance to multiple anti-infectives (CMRNG).221,230,232,233,234,235,239,240,269,292,337

In 2007, CDC altered their guidelines to no longer recommend use of fluoroquinolones for the treatment of gonococcal infections because quinolone-resistant N. gonorrhoeae (QRNG) had become widespread in the US and elsewhere.277,344 As a result, cephalosporins became the only remaining class of anti-infectives that could be considered for the treatment of gonococcal infections.277,344 However, N. gonorrhoeae with reduced susceptibility to ceftriaxone and/or cefixime or other cephalosporins have also been reported with increasing frequency in the US and elsewhere (e.g., Asia, Europe, Canada)344,716,717,718,719,720,721,722,723,724,725,726,727 and there have been rare reports of N. gonorrhoeae with high-level ceftriaxone resistance in some countries (Japan, France, Spain).717,721,727

In 2012, based on evidence of declining cefixime susceptibility among urethral N. gonorrhoeae isolates collected during 2006-2011 in the US and elsewhere and reports of treatment failures with cefixime and other oral cephalosporins in some countries, CDC again altered their guidelines to state that IM ceftriaxone is the cephalosporin of choice for the treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea and that cefixime and other oral cephalosporins should not be used for first-line treatment.344,722

Currently, CDC and other clinicians state that dual combination treatment with ceftriaxone and azithromycin is the regimen of choice for gonococcal infections in the US.344,345 The theoretical basis of dual combination treatment is that the use of 2 anti-infectives with different mechanisms of action against N. gonorrhoeae may improve treatment efficacy and potentially delay emergence and spread of cephalosporin resistance.344 In addition, because individuals with N. gonorrhoeae infection frequently are coinfected with Chlamydia trachomatis , a dual regimen that includes azithromycin provides coverage against such infections.344 Although CDC previously stated that either a single dose of oral azithromycin or a 7-day regimen of oral doxycycline could be used as the second anti-infective in dual treatment regimens, single-dose azithromycin is now preferred because of convenience and compliance advantages and because the prevalence of N. gonorrhoeae resistant to tetracyclines is substantially higher than that reported for azithromycin.344 In patients allergic to azithromycin, multiple-dose doxycycline can be substituted for single-dose azithromycin in recommended or alternative dual treatment regimens.344 Dual treatment regimens should be used in all adults and adolescents with gonorrhea, regardless of the presence or absence of chlamydial coinfection.344,345

HIV-infected individuals should receive the same treatment regimens recommended for other individuals with gonococcal infections.344

CDC recommends that health-care providers treating gonorrhea remain vigilant for treatment failures (evidenced by persistent symptoms or a positive follow-up test despite treatment).344 If there is evidence of treatment failure and reinfection is unlikely, relevant clinical specimens should be obtained for culture (preferable with simultaneous nucleic acid amplification test [NAAT]) and in vitro susceptibility testing should be performed if N. gonorrhoeae is isolated.344 Whenever treatment failure is suspected, an infectious disease specialist, an STD/HIV Prevention Training Center ([Web]), local or state health department STD program, or CDC (404-639-8659) should be consulted for advice on obtaining cultures, in vitro susceptibility testing, and treatment.344 Suspected treatment failures should be reported to CDC through local or state health departments within 24 hours of diagnosis and clinical isolates should be sent to CDC and stored at local laboratories for possible further testing.344

For additional information on management of gonococcal infections, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Gonococcal Infections in Adults and Adolescents

Uncomplicated Cervical, Urethral, and Rectal Gonorrhea

For the treatment of uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents, CDC states that a dual combination regimen that includes a single 250-mg IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose) is the regimen of choice.344 In clinical trials, a single 250-mg IM dose of ceftriaxone was associated with a 99.2% cure rate in patients with uncomplicated urogenital and anorectal gonorrhea.344 There are no clinical data to support a ceftriaxone dose greater than 250 mg for the treatment of uncomplicated gonorrhea.344 Although other parenteral cephalosporins (e.g., a single 500-mg IM dose of cefotaxime or single 2-g IM dose of cefoxitin) are safe and generally effective for the treatment of uncomplicated urogenital and anorectal gonorrhea, these drugs offer no advantage over ceftriaxone for urogenital infections.344

If necessary because ceftriaxone is not available or cannot be used, CDC states that adults and adolescents can receive an alternative dual combination regimen that includes a single 400-mg dose of oral cefixime and a dose of azithromycin (single 1-g oral dose) for the treatment of uncomplicated urogenital or anorectal gonorrhea.344 The oral cefixime regimen does not provide the high, sustained bactericidal blood concentrations provided by IM ceftriaxone and has been associated with a cure rate of 97.5% in patients with uncomplicated urogenital and anorectal gonorrhea.344

In adults and adolescents with cephalosporin allergy, CDC states that a dual treatment regimen that includes a single dose of oral gemifloxacin (320 mg) and a single dose of oral azithromycin (2 g) or a dual treatment regimen that includes a single dose of IM gentamicin (240 mg) and a single dose of oral azithromycin (2 g) could be considered for the treatment of uncomplicated urogenital gonorrhea; however, GI effects may limit use of these regimens.344 If available, spectinomycin (no longer commercially available in the US) is an effective alternative for the treatment of urogenital and anorectal gonorrhea.344 Although monotherapy with a single 2-g dose of oral azithromycin was previously recommended for the treatment of uncomplicated urogenital gonorrhea in patients with cephalosporin allergy, CDC states that monotherapy is no longer recommended because of concerns related to development of resistance and because there have been documented treatment failures with azithromycin monotherapy.344

A test-of-cure follow-up (culture or NAAT) is not usually needed in patients with uncomplicated urogenital or rectal gonorrhea who receive a recommended or alternative dual treatment regimen.344

Uncomplicated Pharyngeal Gonorrhea

For the treatment of uncomplicated gonorrhea of the pharynx† in adults and adolescents, CDC states that a dual combination regimen that includes a single 250-mg IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose) is the regimen of choice.344

Pharyngeal gonococcal infections are more difficult to eradicate than cervical, urethral, or rectal infections.344 Ceftriaxone generally has been effective in the treatment of pharyngeal gonococcal infections;104,115,118,251,336,344 most other anti-infectives, including oral cephalosporins, do not reliably cure such infections.104,115,344 In clinical trials, a single 250-mg IM dose of ceftriaxone was associated with a cure rate of 98.9% in patients with pharyngeal infections.344

A test-of-cure follow-up is not usually needed in patients with uncomplicated pharyngeal gonorrhea who receive the recommended ceftriaxone dual treatment regimen; however, if an alternative regimen is used in patients with pharyngeal gonorrhea, a test-of-cure follow-up (culture or NAAT) is recommended 14 days after treatment.344

Gonococcal Conjunctivitis

The regimen of choice for the treatment of gonococcal conjunctivitis† in adults and adolescents is a dual combination regimen that includes a single IM dose of ceftriaxone and a single dose of oral azithromycin.344 As an adjunct to anti-infective therapy, the infected eye can be irrigated once with sterile sodium chloride solution.344 Because only limited data are available regarding treatment of gonococcal conjunctivitis, consultation with an infectious disease specialist should be considered.344

Disseminated Gonococcal Infections

For initial treatment of disseminated gonococcal infections that include arthritis and arthritis-dermatitis syndrome†, CDC recommends that adults and adolescents receive a dual combination regimen that includes a multiple-dose regimen of IM or IV ceftriaxone and a single dose of oral azithromycin.344 The alternative for initial treatment is a multiple-dose regimen of IV cefotaxime and a single dose of oral azithromycin.344 The initial parenteral regimen should be continued for 24-48 hours after substantial improvement occurs; treatment can then be switched to an oral regimen that is selected based on in vitro susceptibility testing and continued to complete at least 1 week of treatment.344

For the treatment of gonococcal meningitis† or gonococcal endocarditis†, CDC recommends that adults and adolescents receive a dual combination regimen that includes a multiple-dose regimen of IV ceftriaxone and a single dose of oral azithromycin.344 The parenteral regimen should be continued for 10-14 days in patients with meningitis and for at least 4 weeks in patients with endocarditis.344

Initial treatment of disseminated gonococcal infections should be undertaken in consultation with an infectious disease specialist, especially if the diagnosis is uncertain, purulent synovial effusions or other complications are present, or adherence to the regimen is uncertain.344 Evaluation for clinical evidence of endocarditis and meningitis is recommended in all patients with disseminated gonorrhea.344

Gonococcal Epididymitis

Ceftriaxone is a drug of choice for the treatment of acute epididymitis†.344 Although acute epididymitis in sexually active men younger than 35 years of age is most frequently caused by C. trachomatis or N. gonorrhoeae , epididymitis can also be caused by other organisms (e.g., sexually transmitted enteric bacteria, Mycoplasma , Ureaplasma ).344 Presumptive treatment is usually initiated prior to availability of all diagnostic laboratory test results and is selected based on the patient's risk for chlamydia, gonorrhea, and/or enteric bacteria (e.g., E. coli ).344

For empiric treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea†, CDC recommends that adults receive a single dose of IM ceftriaxone given in conjunction with a 10-day regimen of oral doxycycline.344

For empiric treatment of acute epididymitis most likely caused by sexually transmitted chlamydia, gonorrhea, and enteric bacteria†, CDC recommends that adults receive a single dose of IM ceftriaxone given in conjunction with a 10-day regimen of oral levofloxacin or oral ofloxacin.344 CDC states that levofloxacin or ofloxacin monotherapy can be considered for empiric treatment of acute epididymitis most likely caused by enteric bacteria if gonorrhea has been ruled out using gram, methylene blue, or gentian violet microscopy stain.344

Gonococcal Proctitis

For presumptive treatment of acute proctitis† prior to availability of diagnostic laboratory test results, CDC recommends that adults receive a single dose of IM ceftriaxone given in conjunction with a 7-day regimen of oral doxycycline.344

Gonococcal Infections in Neonates

Gonococcal infections in neonates usually occur as the result of exposure to the mother's infected cervical exudate and are apparent 2-5 days after birth.292,344 The most serious manifestations of N. gonorrhoeae infection in neonates are ophthalmia neonatorum and sepsis, arthritis, and meningitis; less serious manifestations include rhinitis, vaginitis, urethritis, and reinfection at sites of fetal monitoring (e.g., scalp).292,344 Because a neonate with gonococcal infection usually has acquired the organism from their mother, both the mother and her sexual partner(s) should be evaluated and treated for gonorrhea.292,344

Prophylaxis and Presumptive Treatment of Gonococcal Infections in Neonates

CDC and AAP recommend routine topical prophylaxis using 0.5% erythromycin ophthalmic ointment in all neonates as soon as possible after birth to prevent gonococcal ophthalmia neonatorum; however, topical anti-infectives are inadequate for prophylaxis of gonococcal infections at other sites and may be ineffective in preventing chlamydial neonatal conjunctivitis.292,344

Because neonates born to women with untreated gonorrhea are at high risk of infection with N. gonorrhoeae , CDC and AAP recommend that such neonates receive a single dose of IM or IV ceftriaxone for parenteral prophylaxis † and presumptive treatment of gonorrhea†.292,344 The single-dose ceftriaxone regimen also is recommended in other neonates if topical ophthalmic erythromycin is unavailable, especially for neonates born to women who are at risk for gonococcal infection or received no prenatal care.344 Topical erythromycin prophylaxis is unnecessary in neonates who receive parenteral prophylaxis with ceftriaxone.292

CDC states that data are not available regarding the use of dual combination treatment regimens in neonates born to women with gonorrhea.344

Gonococcal Ophthalmia Neonatorum

For the treatment of ophthalmia neonatorum† caused by N. gonorrhoeae , CDC and AAP recommend that neonates receive a single dose of IM or IV ceftriaxone.292,344

As an adjunct to parenteral treatment of gonococcal ophthalmia neonatorum, the neonate's eyes should be irrigated with sterile sodium chloride solution immediately and at frequent intervals until the discharge is eliminated.292 Topical anti-infectives are inadequate for the treatment of gonococcal ophthalmia neonatorum and are unnecessary when appropriate systemic anti-infective therapy is given.292,344

Infants born to mothers with untreated gonorrhea are at increased risk for gonococcal ophthalmia neonatorum if they do not receive appropriate parenteral prophylaxis at birth.344 Other neonates at increased risk for gonococcal ophthalmia neonatorum include those with mothers who received no prenatal care or have a history of sexually transmitted diseases or substance abuse.167 In all cases of neonatal conjunctivitis, conjunctival exudate should be cultured for N. gonorrhoeae and tested for anti-infective susceptibility and both mother and infant should be tested for chlamydial infection.344 Although the single-dose ceftriaxone regimen is adequate for treatment of gonococcal conjunctivitis, infants with ophthalmia neonatorum be hospitalized and evaluated for signs of disseminated infection (e.g., sepsis, arthritis, meningitis).292,344 CDC recommends that infants with gonococcal ophthalmia be managed in consultation with an infectious disease specialist.344

Disseminated Gonococcal Infections and Gonococcal Scalp Abscesses in Neonates

Neonates with documented gonococcal infection at any site (including the eyes or scalp) should be evaluated for the possibility of disseminated infection (e.g., sepsis, arthritis, meningitis).292,344 If disseminated gonococcal infection is present, CDC and AAP recommend a multiple-dose regimen of IV or IM ceftriaxone or IV or IM cefotaxime.292,344 While either ceftriaxone or cefotaxime can be used for the treatment of disseminated gonococcal infections in neonates,292,344 ceftriaxone is contraindicated in certain neonates (see Cautions: Pediatric Precautions).1,2,18,30,32,292,344 AAP states that cefotaxime is preferred in infants with hyperbilirubinemia.292

CDC states that data are not available regarding the use of dual combination regimens for the treatment of disseminated gonococcal infections or gonococcal scalp abscesses in neonates.344

Gonococcal Infections in Infants and Children

Uncomplicated Gonorrhea

For the treatment of uncomplicated gonococcal vulvovaginitis, cervicitis, epididymitis, urethritis, pharyngitis, or proctitis in infants and children, CDC and AAP recommend a single dose of IM ceftriaxone.292,344 AAP states that a dual combination treatment regimen that includes a single dose of IM ceftriaxone and a single dose of oral azithromycin can be used for the treatment of uncomplicated gonorrhea in children weighing at least 45 kg.292 CDC states that data are not available regarding the use of dual combination regimens for the treatment of uncomplicated gonorrhea in children weighing 45 kg or less.344

CDC and AAP state that adolescents with uncomplicated gonorrhea should receive a dual combination treatment regimen recommended for adults.292,344 (See Gonococcal Infections in Adults and Adolescents under Uses: Gonorrhea.)

Disseminated Gonococcal Infections

For the treatment of disseminated gonococcal infections† (e.g., bacteremia, arthritis) in infants and children, CDC and AAP recommend a multiple-dose regimen of IM or IV ceftriaxone.292,344 AAP states that a dual combination treatment regimen that includes IM or IV ceftriaxone and oral erythromycin can be used for the treatment of complicated gonococcal infections in children weighing less than 45 kg and a dual combination treatment regimen that includes IM or IV ceftriaxone and oral azithromycin can be used in children weighing at least 45 kg.292 CDC states that data are not available regarding the use of dual combination regimens for the treatment of complicated gonorrhea in children weighing 45 kg or less.344

CDC and AAP state that adolescents with disseminated gonococcal infections should receive a dual combination treatment regimen recommended for adults.292,344 (See Gonococcal Infections in Adults and Adolescents under Uses: Gonorrhea.)

Prophylaxis in Sexual Assault Victims

A single dose of IM ceftriaxone is used in conjunction with a single dose of oral azithromycin and a single dose of either oral metronidazole or oral tinidazole for empiric anti-infective prophylaxis in adult or adolescent victims of sexual assault†.292,344 Gonorrhea, genital chlamydial infection, trichomoniasis, and bacteria vaginosis are the sexually transmitted diseases most commonly diagnosed in women following sexual assault; however, the prevalence of these infections is substantial among sexually active women and their presence after assault does not necessarily indicate that the infections were acquired during the assault.344 Gonococcal and chlamydial infections among females are of special concern because of the possibility of ascending infection.344

CDC recommends routine empiric prophylaxis after a sexual assault, and use of such prophylaxis probably benefits most patients since follow-up of assault victims can be difficult and such prophylaxis allays the patient's concerns about possible infections.344 The 3-drug empiric anti-infective prophylaxis regimen recommended for adults and adolescents (ceftriaxone, azithromycin, and either metronidazole or tinidazole) provides coverage against gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, but efficacy in preventing these infections after sexual assault has not been evaluated.344 Patients should be counseled regarding the potential benefits and toxicities associated with the regimen (e.g., GI effects).344

Routine postexposure vaccination with hepatitis B virus (HBV) vaccine also is recommended for adult and adolescent sexual assault victims who have not previously received the vaccine or whose immunity against HBV is uncertain; hepatitis B immune globulin also should be given to previously unvaccinated individuals if the assailant is known to be hepatitis B surface antigen (HBsAg)-positive.292,344 In addition, vaccination with human papillomavirus (HPV) vaccine is recommended for previously unvaccinated or incompletely vaccinated female assault victims 9-26 years of age and male assault victims 9-21 years of age.344 CDC states that a decision to offer antiretroviral postexposure prophylaxis against HIV should be individualized taking into account the probability of HIV transmission (e.g., likelihood of the assailant having HIV, exposure characteristics that might increase the risk for HIV transmission, time elapsed after the event) and potential benefits and risks of such prophylaxis.344 (See Guidelines for Use of Antiretroviral Agents: Antiretrovirals for Postexposure Prophylaxis following Sexual, Injection Drug Use, or other Nonoccupational Exposures to HIV [nPEP], in the Antiretroviral Agents General Statement 8:18.08.)

Pelvic Inflammatory Disease !!navigator!!

Ceftriaxone is used for the treatment of pelvic inflammatory disease (PID) caused by N. gonorrhoeae .1,2,3,18,30,32,292,344,345,397,398,460 Ceftriaxone, like other cephalosporins, generally is inactive against C. trachomatis and should not be used alone in the treatment of PID.1,2,3,18,30,32,344

PID is an acute or chronic inflammatory disorder in the upper female genital tract and can include any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis.344,398 PID generally is a polymicrobial infection most frequently caused by N. gonorrhoeae and/or Chlamydia trachomatis ; however, organisms that can be part of the normal vaginal flora (e.g., anaerobic bacteria, Gardnerella vaginalis , H. influenzae , enteric gram-negative bacilli, S. agalactiae ) or mycoplasma (e.g., Mycoplasma hominis , Ureaplasma urealyticum ) also may be involved.292,344,345,397,398 PID is treated with an empiric regimen that provides broad-spectrum coverage.292,344,345,397,398 The regimen should be effective against N. gonorrhoeae and C. trachomatis and also probably should be effective against anaerobes.344,398,399 The optimum empiric regimen for the treatment of PID has not been identified.344 A variety of parenteral and oral regimens have been shown to achieve clinical and microbiologic cure in randomized studies with short-term follow-up.397,399,344

IV Regimens for PID

When a parenteral regimen is indicated for the treatment of PID, CDC and other clinicians generally recommend a 2-drug regimen of cefoxitin (2 g IV every 6 hours) or cefotetan (2 g IV every 12 hours) given in conjunction with doxycycline (100 mg IV or orally every 12 hours) or a 2-drug regimen of clindamycin (900 mg IV every 8 hours) and gentamicin (usually a 2-mg/kg IV or IM loading dose followed by 1.5 mg/kg every 8 hours; regimen of 3-5 mg/kg once daily can be substituted).344,345,399 While certain parenteral cephalosporins (e.g., cefotaxime, ceftriaxone) also have been used and may be effective for the treatment of PID,344,397,398,460 CDC states that there is less experience with use of these cephalosporins in patients with PID and these drugs may be less active than cefotetan or cefoxitin against anaerobic bacteria.344

The parenteral regimen should be continued until 24-48 hours after the patient improves clinically and then, based on clinical experience, a transition to an oral regimen can be considered to complete 14 days of treatment.344 If tubo-ovarian abscess is present, at least 24 hours of inpatient observation is recommended.344

IM and Oral Regimens for PID

In women with mild to moderately severe acute PID, CDC states that an IM and oral regimen can be considered since clinical outcomes with these regimens are similar to IV regimens in such patients.344 However, if there is no response to the IM and oral regimen within 72 hours, the patient should be reevaluated to confirm the diagnosis and an IV regimen initiated.344

If an IM and oral regimen is used, CDC recommends a single dose of an IM cephalosporin (e.g., ceftriaxone, cefoxitin with oral probenecid, cefotaxime) given in conjunction with a 14-day regimen of oral doxycycline (with or without oral metronidazole).344 The optimal cephalosporin is unclear; although cefoxitin usually has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae .344

For additional information on management of PID, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Actinomycosis !!navigator!!

Ceftriaxone has been used in a limited number of patients to treat infections caused by Actinomyces †.278,380,381 IV ceftriaxone has been effective when given on an outpatient basis for the treatment of thoracic actinomycosis.381 However, IV penicillin G generally is the drug of choice for initial treatment of all forms of actinomycosis, including thoracic, abdominal, genitourinary, CNS, and cervicofacial infections.197,263,278,292,382 Alternative anti-infectives that can be used for the treatment of actinomycosis include amoxicillin, tetracyclines, erythromycins, chloramphenicol, clindamycin, third generation cephalosporins, and meropenem.197,292,382

Bartonella Infections !!navigator!!

IM or IV ceftriaxone has been used in conjunction with oral erythromycin or oral azithromycin for the treatment of bacteremia caused by Bartonella quintana † (formerly Rochalimaea quintana ).396 B. quintana , a gram-negative bacilli, can cause cutaneous bacillary angiomatosis, trench fever, bacteremia, endocarditis, and chronic lymphadenopathy.396,400,464,465 B. quintana infections have been reported most frequently in immunocompromised patients (e.g., HIV-infected individuals), homeless individuals in urban areas, and chronic alcohol abusers.396,400,440,465 Optimum anti-infective regimens for the treatment of infections caused by B. quintana have not been identified,396,464,465 and various drugs have been used or are recommended to treat these infections, including doxycycline, erythromycin, azithromycin, clarithromycin, chloramphenicol, or cephalosporins.197,292,440,464,465 There is evidence that these B. quintana infections tend to persist or recur and prolonged therapy (several months or longer) usually is necessary.396,440,465

The possible role of ceftriaxone in the treatment of infections caused by Bartonella henselae † (formerly Rochalimaea henselae ) (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis) has not been determined.443 Cat scratch disease generally is a self-limited illness in immunocompetent individuals and may resolve spontaneously in 2-4 months; however, some clinicians suggest that anti-infective therapy be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and such therapy probably is indicated in immunocompromised patients.292,440,443,444,445 Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud's oculoglandular syndrome.292,443,444,445 While the optimum anti-infective regimen for the treatment of cat scratch disease or other B. henselae infections has not been identified, some clinicians recommend azithromycin, clarithromycin, erythromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.197,292,440,442,443,444,445

In HIV-infected patients, Bartonella infections occur most frequently in those with median CD4+ T-cell counts less than 50 cells/mm3.440 CDC, NIH, and IDSA recommend that all HIV-infected adults and adolescents diagnosed with a Bartonella infection receive at least 3 months of antibacterial treatment; if relapse occurs, long-term suppressive antibacterial treatment (secondary prophylaxis) may be needed.440 For initial treatment or long-term suppressive therapy of Bartonella infections in HIV-infected adults or adolescents, doxycycline or a macrolide (erythromycin, azithromycin, clarithromycin) is recommended.440 Although pregnant HIV-infected women should usually receive a macrolide (erythromycin) for treatment of these infections, CDC, NIH, and IDSA state that ceftriaxone may be a possible alternative when macrolides cannot be used.440

Capnocytophaga Infections !!navigator!!

Based on results of in vitro susceptibility tests that indicate that Capnocytophaga generally is inhibited by ceftriaxone,461,462 some clinicians suggest that ceftriaxone can be used in the treatment of infections caused by C. canimorsus † (formerly CDC group DF-2).197 Capnocytophaga is a gram-negative bacilli that can cause life-threatening septicemia, meningitis, and/or endocarditis and often is associated with disseminated intravascular coagulation; splenectomized and immunocompromised individuals are at particularly high risk for serious Capnocytophaga infections.480 C. canimorsus infection usually occurs as the result of a dog bite or other close contact with a dog.463 The optimum regimen for the treatment of infections caused by Capnocytophaga has not been identified, but some clinicians recommend penicillin G197,463 or, alternatively, a third generation cephalosporin (cefotaxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.197

Leptospirosis !!navigator!!

Ceftriaxone is used in the treatment of severe leptospirosis† caused by Leptospira .292,690,694,695 Leptospirosis is a spirochete infection that may range in severity from an asymptomatic or subclinical illness that is self-limited to a severe, life-threatening illness that includes jaundice, renal failure, hemorrhage, cardiac arrhythmias, pneumonitis, and hemodynamic collapse (Weil syndrome).292,691,693

Penicillin G generally has been considered the drug of choice for the treatment of moderate to severe leptospirosis,197,292,690,691,695 and doxycycline has been used in less severe infections.197,292 Other anti-infectives recommended for the treatment of severe leptospirosis include cephalosporins (ceftriaxone, cefotaxime), aminopenicillins (ampicillin, amoxicillin), tetracyclines (doxycycline, tetracycline), or macrolides (azithromycin).197,292,691,693,694,695

In one randomized study in adults, IV ceftriaxone was as effective as IV penicillin G for the treatment of severe leptospirosis.690 The duration of fever was decreased to 3 days in both treatment groups, and there were comparable improvements in complications associated with the infection (renal failure, respiratory failure, liver impairment, thrombocytopenia).690

Lyme Disease !!navigator!!

Ceftriaxone is used in the treatment of Lyme disease†.197,292,329,342,357,358,359,361,362,363,364,365,366,367,481,492 IDSA, AAP, and other clinicians recommend IV ceftriaxone as a drug of choice for the treatment of early neurologic Lyme disease† with acute neurologic manifestations such as meningitis or radiculopathy, Lyme carditis†, Lyme arthritis†, and late neurologic Lyme disease†.292,329,342,357,358,359,361,362,363,364,365,366,367,481,492

Lyme disease is a tick-borne spirochetal disease.207,261,314,329,481,497 In the US, Lyme disease is caused by the spirochete Borrelia burgdorferi , which is transmitted by the bite of Ixodes scapularis or I. pacificus ticks.207,261,314,329,481,497 For additional information on Lyme disease, see Lyme Disease in Uses: Spirochetal Infections, in the Tetracyclines General Statement 8:12.24.

Early Lyme Disease

Erythema Migrans

Oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil) generally are effective for the treatment of early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations or advanced atrioventricular (AV) heart block.279,292,329,353,356,357,358,359,361,362,363,365,366,367,481 Although IV ceftriaxone is effective for early Lyme disease manifested as erythema migrans, it is not superior to the recommended oral drugs and is more likely to cause serious adverse effects; therefore, ceftriaxone is not usually recommended for the treatment of early Lyme disease in the absence of neurologic involvement or advanced AV heart block.329

Early Neurologic Lyme Disease

Ceftriaxone is a drug of choice for the treatment of early neurologic Lyme disease†.279,292,329,353,356,357,358,359,361,362,363,365,366,367,481 Parenteral anti-infectives are recommended for the treatment of early Lyme disease when there are acute neurologic manifestations such as meningitis or radiculoneuritis.197,279,292,329,353,356,357,358,359,361,362,363,365,366,367,481

IDSA and other clinicians recommend a 14-day regimen (range: 10-28 days) of IV ceftriaxone as the preferred parenteral regimen for the treatment of acute neurologic Lyme disease manifested by meningitis or radiculopathy; IV cefotaxime and IV penicillin G sodium are the preferred alternatives.292,329,497,498 In patients with acute neurologic manifestations who are intolerant of cephalosporins and penicillin, there is some evidence that oral doxycycline may be an adequate alternative that can be considered for use in adults and children 8 years of age or older.329

Lyme Carditis

Ceftriaxone is the drug of choice when a parenteral regimen is indicated for the treatment of Lyme carditis†.292,329,497 IDSA states that patients with AV heart block and/or myopericarditis associated with early Lyme disease may be treated with a 14-day regimen (range: 14-21 days) of oral or parenteral anti-infectives.329 Although there is no evidence to date to suggest that a parenteral regimen is more effective than an oral regimen for the treatment of Lyme carditis, a parenteral regimen usually is recommended for initial treatment of hospitalized patients; an oral regimen can be used to complete therapy and for the treatment of outpatients.292,329,497 When a parenteral regimen is used, IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium is recommended.292,329,497 When an oral regimen is used, doxycycline, amoxicillin, or cefuroxime axetil is recommended.292,329,497

Because of the potential for life-threatening complications, hospitalization and continuous monitoring is advisable for patients who are symptomatic (syncope, dyspnea, chest pain) and also is recommended for those with second- or third-degree AV block or first-degree heart block when the PR interval is prolonged to 0.3 seconds or longer.329,497 Patients with advanced heart block may require a temporary pacemaker and consultation with a cardiologist is recommended.329,497

Late Lyme Disease

Lyme Arthritis

Ceftriaxone is the drug of choice when a parenteral regimen is indicated for the treatment of Lyme arthritis†.292,329,497,498 While patients with uncomplicated Lyme arthritis without clinical evidence of neurologic disease generally can be treated with a 28-day oral regimen (doxycycline, amoxicillin, or cefuroxime axetil),329,497,498 IDSA and other clinicians state that patients with Lyme arthritis and concomitant neurologic disease should receive a 14-day parenteral regimen (range: 14-28 days) of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G.292,329,497,498 While oral regimens are easier to administer, associated with fewer serious adverse effects, and less expensive than IV regimens, some patients with Lyme arthritis treated with oral anti-infectives have subsequently developed overt neuroborreliosis, which may require IV therapy for successful resolution.329 Therefore, additional study is needed to fully evaluate the comparative safety and efficacy of oral versus IV anti-infectives for the treatment of Lyme arthritis.329

In patients who have persistent or recurrent joint swelling after a recommended oral regimen, IDSA and other clinicians recommend retreatment with the oral regimen or a switch to a parenteral regimen.329,497 Some clinicians prefer retreatment with an oral regimen for patients whose arthritis substantively improved but did not completely resolve; these clinicians reserve parenteral regimens for those patients whose arthritis failed to improve or worsened.329 It has been suggested that clinicians should consider allowing several months for joint inflammation to resolve after initial treatment before an additional course of anti-infectives is given.329

Late Neurologic Lyme Disease

Ceftriaxone is the drug of choice for the treatment of late neurologic Lyme disease†.292,329 IDSA and other clinicians state that patients with late neurologic Lyme disease affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy) should receive 2-4 weeks of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium.292,329 Response to anti-infective treatment usually is slow and may be incomplete in patients with late neurologic Lyme disease.329 IDSA states that retreatment is not recommended unless relapse is documented with reliable objective measures.329

In a limited number of adults with late complications of Lyme disease (i.e., CNS dysfunction, peripheral neuropathy, and/or arthritis), most of whom failed to respond adequately to other anti-infectives (e.g., penicillin, tetracycline), ceftriaxone therapy (1 or 2 g IM or IV twice daily for 14 days) resulted in clinical improvement, including resolution of arthritis and chronic fatigue.207,261,314 A regimen of IV ceftriaxone (2 g once daily for 30 days) has been used with some success for the treatment of Lyme encephalopathy.492 Although IV penicillin G therapy can be effective in treating neurologic abnormalities of Lyme disease, central or peripheral neurologic deficits associated with disease progression have been noted in a few patients after such therapy,287 and some clinicians suggest that therapy with IV ceftriaxone may be preferred for serious manifestations (i.e., involving major organs) of disseminated or late Lyme disease because of its greater in vitro and in vivo activity against B. burgdorferi compared with IV penicillin G and the prolonged serum concentrations and excellent CSF penetration achievable with once-daily administration of ceftriaxone.276,279,280,283,284,285,286,290,314,329

Neisseria meningitidis Infections !!navigator!!

Ceftriaxone is used in the treatment of invasive infections caused by N. meningitidis 1,2,3,18,30,32,166,292 and also is used to eliminate nasopharyngeal carriage of N. meningitidis † and for chemoprophylaxis to prevent meningococcal disease in close contacts of patients with invasive disease†.166,292,376

For suspected meningococcal disease, including presumptive N. meningitidis meningitis, AAP and IDSA recommend a third generation cephalosporin (ceftriaxone or cefotaxime) for initial empiric treatment.292,418 If the infection is found to be caused by penicillin-susceptible N. meningitidis , IV penicillin G or ampicillin can be substituted or the third generation cephalosporin can be continued.292 Although IV penicillin G generally has been considered the drug of choice for the treatment of meningitis known to be caused by susceptible N. meningitidis ,166,292,418 some experts recommend ampicillin, ceftriaxone, or cefotaxime.292,418

Patients with invasive meningococcal disease who have been treated with penicillin G or any anti-infective agent other than ceftriaxone or another third generation cephalosporin may still be carriers of N. meningitidis and should receive an anti-infective regimen to eradicate nasopharyngeal carriage of the organism prior to hospital discharge.166,292,376 The treatments of choice to eradicate nasopharyngeal carriage of N. meningitidis are ceftriaxone (single IM dose), rifampin (2-day regimen), and ciprofloxacin (single oral dose).166,292,376 These regimens are all 90-95% effective and any of these is an acceptable regimen in appropriate patients.166,376

Chemoprophylaxis in Household and Other Close Contacts of Individuals with Invasive Meningococcal Disease

Chemoprophylaxis in close contacts of a patients with invasive meningococcal disease is an important means of preventing secondary cases in household and other close contacts.166,292,376 Recommended regimens for chemoprophylaxis against meningococcal disease include a single dose of IM ceftriaxone, 2-day regimen of oral rifampin (not recommended in pregnant women), or a single dose of oral ciprofloxacin (not recommended in individuals younger than 18 years of age unless no other regimen can be used and not recommended for pregnant or lactating women).166,292,376 These regimens are all 90-95% effective and any of these is an acceptable regimen for chemoprophylaxis.166,376 AAP suggests that rifampin may be the drug of choice for chemoprophylaxis in most children.292

The attack rate for household contacts who do not receive chemoprophylaxis has been estimated to be 4 cases per 1000 individuals exposed, which is 500-800 times greater than that for the general population.292,376 A decision to administer chemoprophylaxis to close contacts of an individual with invasive meningococcal disease is based on the degree of risk.292,376 Throat and nasopharyngeal cultures are not useful in determining the need for chemoprophylaxis and may unnecessarily delay administration of the regimen.292,376

The USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend that chemoprophylaxis be administered to contacts of patients with invasive meningococcal disease who are considered at high risk of infection.166,292,376 These high risk individuals include household contacts (especially children younger than 2 years of age) and any individual who has slept or eaten frequently in the same dwelling with the index case; child care and nursery school contacts who were exposed during the 7 days before the onset of disease in the index case; individuals exposed directly to oropharyngeal secretions of the index case (e.g., through kissing or sharing toothbrushes, eating utensils, or drinking containers) during the 7 days before the onset of disease in the index case; and medical personnel and others who had intimate exposure (e.g., through mouth to mouth resuscitation or unprotected contact during endotracheal intubation or suctioning) to the index case during the 7 days before the onset of disease.166,292,376 For travelers, chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index case or for anyone seated directly next to an index case on a prolonged flight (i.e., lasting 8 hours or longer).166,292,376

Chemoprophylaxis is not routinely recommended for contacts of patients with invasive meningococcal disease who are considered at low risk of infection.292 Individuals considered in most circumstances as being at low risk include casual contacts with no history of direct exposure to the index case's oral secretions (e.g., school or work contacts); individuals who had only indirect contact with the index case (only contact was with a high-risk contact of the index case); and medical personnel who had no direct exposure to the index case's oral secretions.292 Because reports of secondary cases after close contact with patients with noninvasive pneumonia or conjunctivitis caused by N. meningitidis are rare, chemoprophylaxis is not recommended for close contacts of patients who only have evidence of N. meningitidis in nonsterile sites (e.g., oropharyngeal, conjunctival, endotracheal secretions).376

When chemoprophylaxis is indicated in high-risk contacts, it must be administered promptly (ideally within 24 hours after identification of the index case) since the attack rate of secondary disease is greatest in the few days following disease onset in the index case.166,292,376 All high-risk contacts should be informed that even if chemoprophylaxis is taken or started, the development of any suspicious clinical manifestation warrants early, rapid medical attention.166 Chemoprophylaxis probably is of limited or no value if administered more than 14 days after contact with the index case.166,376 If high-risk exposure to a new index case occurs more than 2 weeks after initial chemoprophylaxis, additional chemoprophylaxis is indicated.166

Outbreak Control

When an outbreak of meningococcal disease occurs in the US and the outbreak is caused by a vaccine-preventable meningococcal strain (e.g., serogroups A, C, Y, or W-135), large-scale vaccination programs with meningococcal polysaccharide vaccine in the appropriate target group may be indicated.292,376 (See Uses: Outbreak Control in Meningococcal Polysaccharide Vaccine 80:12.) Mass chemoprophylaxis programs (i.e., administration of ceftriaxone, rifampin, or ciprofloxacin to large population groups) are not recommended to control large outbreaks since the disadvantages of such programs (e.g., costs, difficulty in ensuring simultaneous administration of the anti-infectives to large populations, adverse effects of the drugs, emergence of resistant organisms) probably outweigh any possible benefit in disease prevention.376 However, when outbreaks involve limited populations (e.g., a single school), administration of chemoprophylaxis to all individuals in the population may be considered, especially if the outbreak involves a meningococcal serogroup not represented in currently available meningococcal vaccines.376 Other measures, such as restricting travel to areas with a suspected meningococcal outbreak, closing schools or universities, or canceling sporting or social events, are not usually recommended to control meningococcal outbreaks in the US.376

While the vast majority of cases of meningococcal disease in the US are sporadic, localized outbreaks of meningococcal disease do occur.376 When a suspected outbreak of meningococcal disease occurs in the US, public health authorities will then determine whether mass vaccinations (with or without mass chemoprophylaxis) is indicated and delineate the target population based on risk assessment.292,376

Nocardia Infections !!navigator!!

Ceftriaxone has been used for the treatment of nocardiosis† caused by Nocardia .197,292,697,698,699,700,701,702

Co-trimoxazole (fixed combination of sulfamethoxazole and trimethoprim) usually is considered the drug of choice for the treatment of nocardiosis.197,292 Other drugs that have been used alone or in combination regimens for the treatment of nocardiosis include a sulfonamide alone (sulfamethoxazole [not commercially available in the US], sulfadiazine), amikacin, tetracyclines, cephalosporins (ceftriaxone, cefotaxime, cefuroxime), cefoxitin, carbapenems (imipenem, meropenem), fixed combination of amoxicillin and clavulanate, clarithromycin, cycloserine, or linezolid.197,292,697,698,700,701,702 A regimen of amikacin and ceftriaxone has been effective for the treatment of disseminated N. asteroides infection complicated by cerebral abscess.698

Ceftriaxone has been recommended as one of several alternatives to co-trimoxazole for the treatment of skin and skin structure infections caused by Nocardia † (e.g., N. farcinica , N. brasiliensis ).543 Prolonged anti-infective treatment (6-24 months) and/or a multiple-drug anti-infective regimen may be necessary for severe or disseminated infections or in patients with immunosuppression.543

In vitro susceptibility testing, if available, is recommended to guide selection of anti-infectives for the treatment of severe nocardiosis or for treatment in patients who cannot tolerate or failed to respond to sulfonamide treatment.292

Relapsing Fever !!navigator!!

Ceftriaxone may be effective for the treatment of relapsing fever† caused by Borrelia recurrentis ;264 however, other drugs (e.g., tetracycline, penicillin G) are considered the drugs of choice for the treatment of the disease.197,292

Syphilis !!navigator!!

Ceftriaxone has some activity against Treponema pallidum 173 and there is some limited evidence that the drug may be effective for the treatment of syphilis†.216,228,260,344

IM penicillin G benzathine is the drug of choice for the treatment of primary syphilis (i.e., ulcer or chancre at infection site), secondary syphilis (i.e., manifestations that include, but are not limited to, rash, mucocutaneous lesions, and lymphadenopathy), and tertiary syphilis (i.e., cardiac, gummatous lesions, tabes dorsalis, and general paresis) in adults, adolescents, and children.344,345,350,440 IM penicillin G benzathine also is the drug of choice for the treatment of latent syphilis (i.e., detected by serologic testing but lacking clinical manifestations), including both early latent syphilis (latent syphilis acquired within the preceding year) and late latent syphilis (i.e., all other cases of latent syphilis or syphilis of unknown duration) in all age groups.344,345,350,440 For the treatment of neurosyphilis and otic or ocular syphilis, IV penicillin G potassium or sodium is the drug of choice and IM penicillin G procaine (with oral probenecid) is an alternative if compliance can be ensured.344,345,440

CDC states that limited clinical studies as well as biologic and pharmacologic evidence suggest that a multiple-dose ceftriaxone regimen may be effective for the treatment of primary and secondary syphilis† and, on the basis of biologic plausibility and pharmacologic properties, may also be effective for the treatment of latent syphilis† in penicillin-allergic patients.344 However, optimal dosage and duration of ceftriaxone for the treatment of syphilis have not been defined and there is more extensive clinical experience using tetracyclines (doxycycline, tetracycline) as alternatives for the treatment of primary, secondary, or latent syphilis in penicillin-allergic patients.344

CDC states that limited data suggest that a multiple-dose ceftriaxone regimen can be used as an alternative for the treatment of neurosyphilis† in penicillin-allergic patients.344

Decisions regarding the treatment of syphilis in penicillin-allergic patients should be made in consultation with a specialist.344 Because of limited experience with penicillin alternatives, close follow-up is essential if ceftriaxone is used for the treatment of syphilis in penicillin-allergic patients and the possibility of cross-sensitivity between penicillin and ceftriaxone should be considered.344 If compliance with an alternative regimen or follow-up cannot be ensured, CDC recommends desensitization and treatment with the appropriate penicillin G preparation.344

Data are insufficient to recommend use of ceftriaxone or other alternatives for the treatment of any stage of syphilis in penicillin-allergic pregnant women or for the treatment of congenital syphilis in neonates, infants, or children with known or suspected penicillin allergy; CDC recommends that such patients be desensitized and treated with the appropriate penicillin G preparation.344

In certain circumstance when there is a penicillin shortage and penicillin G is not available, CDC states that a multiple-dose ceftriaxone regimen can be considered for the treatment of congenital syphilis.344 In such situations, CDC recommends that ceftriaxone be used with close clinical, serologic, and CSF follow-up and in consultation with a specialist in the treatment of infants with congenital syphilis.344

For additional information on management of syphilis, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Typhoid Fever and Other Invasive Salmonella Infections !!navigator!!

Ceftriaxone has been effective when used in adults or children for the treatment of typhoid fever† or paratyphoid fever† (enteric fever) or septicemia caused by Salmonella serovars Typhi or Paratyphi, respectively, including multidrug-resistant strains.167,188,267,406,407,408,409,410 Ceftriaxone also has been used and is recommended for the treatment of invasive infections (e.g., bacteremia, osteomyelitis) caused by nontyphoidal Salmonella , including Salmonella serovar Typhimurium.292,410,505,590

Multidrug-resistant strains of Salmonella serovar Typhi (i.e., strains resistant to ampicillin, chloramphenicol, and/or co-trimoxazole) have been reported with increasing frequency, and third generation cephalosporins (e.g., ceftriaxone, cefotaxime) and fluoroquinolones (e.g., ciprofloxacin, ofloxacin) are considered the drugs of first choice for the treatment of typhoid fever or other severe infections known or suspected to be caused by these strains.197,292,403,404,405,406,410,411 AAP states that ceftriaxone is a drug of choice for empiric treatment of enteric fever pending results of in vitro susceptibility tests.292 Strains of S. typhi resistant to ceftriaxone have been reported rarely in the US,405

IV ceftriaxone (3 or 4 g once daily in adults or 75 mg/kg once daily in children) given for 5-7 days has been as effective as a 14-day course of oral or IV chloramphenicol in the treatment of typhoid fever caused by susceptible S. typhi .267,407 Although bacteremia resolved sooner with ceftriaxone in some patients, the time to defervescence was faster with chloramphenicol.267,407

Whipple's Disease !!navigator!!

Ceftriaxone has been effective when used in the treatment of Whipple's disease†, a progressive systemic infection caused by Tropheryma whipplei (formerly Tropheryma whippelii ).383,384,385,386,730,731,732 Optimal regimens for the treatment of Whipple's disease have not been identified, in part because of difficulties in identifying and cultivating the causative agent and because relapses commonly occur, even after adequate and long-term anti-infective treatment.383 Some clinicians recommend an initial parenteral regimen (e.g., ceftriaxone or penicillin G used with or without streptomycin) followed by a long-term regimen of oral co-trimoxazole given for 1-2 years.730,732

Ceftriaxone has been effective for the treatment of Whipple's disease when the CNS was involved.384,385,386 For the treatment of encephalitis caused by T. whipplei , IDSA recommends initial treatment with ceftriaxone given for 2-4 weeks followed by co-trimoxazole or cefixime for 1-2 years.506 Some clinicians suggest that ceftriaxone may be a drug of choice for patients who experience cerebral relapse during or after treatment with penicillin G or co-trimoxazole.385

Empiric Therapy in Febrile Neutropenic Patients !!navigator!!

Ceftriaxone has been used in conjunction with an aminoglycoside for empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic adults or pediatric patients†.387,388,437 While ceftriaxone has been used alone for empiric therapy in some febrile neutropenic patients considered to be at low risk,453,454 use of ceftriaxone monotherapy may not provide adequate coverage against some potential pathogens (e.g., Ps. aeruginosa ) and generally is not recommended for empiric anti-infective therapy in febrile neutropenic patients.435,436

In studies in febrile neutropenic cancer patients 1 year of age or older, the overall response rate to a once-daily regimen of IV ceftriaxone (30 mg/kg once daily in adults or 80 mg/kg once daily in children) given in conjunction with IV amikacin (20 mg/kg daily) was similar to that of a regimen of IV ceftazidime (100-150 mg/kg daily given in 3 divided doses) given in conjunction with amikacin (20 mg/kg given once daily or in 3 divided doses).387,388

Published protocols for the treatment of infections in febrile neutropenic patients should be consulted for specific recommendations regarding selection of the initial empiric anti-infective regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.457 In addition, consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients is advised.457

Prevention of Bacterial Endocarditis !!navigator!!

Ceftriaxone is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in adults and children undergoing certain dental or upper respiratory tract procedures who have certain cardiac conditions that put them at the highest risk of adverse outcome from endocarditis.451

The cardiac conditions identified by AHA as those associated with highest risk of adverse outcomes from endocarditis and for which anti-infective prophylaxis is reasonable are prosthetic cardiac valves or prosthetic material used for cardiac valve repair, previous infective endocarditis, cardiac valvulopathy after cardiac transplantation, and certain forms of congenital heart disease (i.e., unrepaired cyanotic congenital heart disease including palliative shunts and conduits; a completely repaired congenital heart defect where prosthetic material or device was placed by surgery or catheter intervention within the last 6 months; repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibits endothelialization).451

AHA states that anti-infective prophylaxis for prevention of α-hemolytic (viridans group) streptococcal bacterial endocarditis is reasonable for patients with the above cardiac risk factors if they are undergoing any dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa (e.g., biopsies, suture removal, placement of orthodontic bands).451 AHA states that anti-infective prophylaxis is not needed for routine anesthetic injections through noninfected tissue, dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement of orthodontic brackets, shedding of deciduous teeth, or bleeding from trauma to the lips or oral mucosa.451

AHA states that anti-infective prophylaxis for prevention of bacterial endocarditis also is reasonable for patients with the above cardiac risk factors if they are undergoing invasive procedures of the respiratory tract that involve incision or biopsy of respiratory mucosa (e.g., tonsillectomy, adenoidectomy) and may be reasonable for such patients if they are undergoing surgical procedures that involve infected skin, skin structure, or musculoskeletal tissue.451 However, anti-infective prophylaxis solely to prevent infective endocarditis is no longer recommended by AHA for GI or genitourinary tract procedures.451

Oral amoxicillin is the drug of choice when prevention of bacterial endocarditis is indicated in patients undergoing certain dental or upper respiratory tract procedures who have certain cardiac conditions that put them at highest risk of adverse outcomes from endocarditis.451 If an oral regimen cannot be used in such patients, AHA recommends IM or IV ampicillin or IM or IV cefazolin or ceftriaxone.451 Alternatives for penicillin-allergic patients include oral cephalexin, oral azithromycin or clarithromycin, oral or parenteral clindamycin, or parenteral cefazolin or ceftriaxone; cephalosporins should not be used for such prophylaxis in individuals with a history of anaphylaxis, angioedema, or urticaria after receiving a penicillin.451

For additional information on which cardiac conditions are associated with the highest risk of adverse outcomes from endocarditis and additional information regarding use of prophylaxis to prevent bacterial endocarditis, current recommendations published by AHA should be consulted.451

Perioperative Prophylaxis !!navigator!!

Ceftriaxone has been used perioperatively to reduce the incidence of infection in patients undergoing certain contaminated or potentially contaminated surgical procedures,1,2,18,30,32 including biliary tract procedures (e.g., cholecystectomy),1,2,18,30,32,147,152,294,295,296,297,298,374,449 colorectal procedures,374 intra-abdominal surgery,152,413 or vaginal or abdominal hysterectomy,1,2,18,30,32,154 and in those undergoing certain clean surgical procedures in which the development of infection at the surgical site would represent a serious risk,1,2,18,30,32 including coronary artery bypass,1,2,18,30,32 open heart surgery,67,105,151 thoracic surgery,500 or orthopedic surgery.105,153 The drug also has been used perioperatively in patients undergoing transurethral resection of the prostate†148,155,509 or renal transplantation†.374

Ceftriaxone in conjunction with metronidazole is one of several options recommended for perioperative prophylaxis in patients undergoing colorectal surgery.360,374 Ceftriaxone also is one of several options recommended for perioperative prophylaxis in patients undergoing biliary tract procedures, but should not be used in those undergoing cholecystectomy for noninfected biliary conditions, including biliary colic or dyskinesia without infection.374

A first or second generation cephalosporin (e.g., cefazolin, cefuroxime) generally is preferred when a cephalosporin is used for perioperative prophylaxis.360,374 Third generation cephalosporins (e.g., cefotaxime, ceftriaxone, ceftazidime) and fourth generation cephalosporins (e.g., cefepime) are not usually recommended for routine perioperative prophylaxis because they are expensive, some are less active than first or second generation cephalosporins against staphylococci, they have spectrums of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis may promote emergence of resistant organisms.360,435 (See Uses: Perioperative Prophylaxis, in the Cephalosporins General Statement 8:12.06.)

Dosage and Administration ⬆ ⬇

[Section Outline]

Reconstitution and Administration !!navigator!!

Ceftriaxone sodium is administered by IV infusion1,2,3,18,30,32 or deep IM injection.1,2

Ceftriaxone should not be administered intrathecally.416

Ceftriaxone has been administered IM or IV to adults or children in outpatient settings, including clinicians' offices, outpatient clinics, infusion centers, skilled nursing facilities, rehabilitation centers, or the patient's home, for the treatment of certain infections suitable for community-based parenteral anti-infective agent therapy (e.g., community-acquired pneumonia, osteomyelitis, endocarditis†).126,132,150,206,246,380,381,415,417,421,422,423,424,425,426,437,450 Outpatient parenteral anti-infective therapy often is used to complete a course of ceftriaxone therapy initiated during hospitalization, but ceftriaxone therapy also has been initiated on an outpatient basis.125,415,423,424,425,426 Ceftriaxone usually is administered in the outpatient setting by a healthcare provider;125,246,415,421,423,424,437 however, the drug has been self-administered in the patients' home by the patient, family member, or other responsible person.126,132,150

Ceftriaxone should not be reconstituted with or further diluted with diluents containing calcium (e.g., Ringer's/lactated Ringer's solution, Hartmann's solution) because a precipitate can form.1,2,3,18,30,32,507,511,529 (See Interaction with Calcium-containing Products under Cautions: Precautions and Contraindications.)

Because precipitation of ceftriaxone-calcium can occur, ceftriaxone must not be admixed with calcium-containing solutions and must not be administered simultaneously with calcium-containing IV solutions, including continuous infusions of calcium-containing solutions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age).1,2,3,18,30,32,507,510,511,529 In adult and pediatric patients older than 28 days of age, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid (e.g., 0.9% sodium chloride injection, 5% dextrose injection).1,2,3,18,30,32,529

Ceftriaxone is contraindicated in neonates (28 days of age or younger) if they are receiving (or expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition.1,2,18,30,529

Patients receiving ceftriaxone should be adequately hydrated.1,2,3,18,32

Intermittent IV Infusion

For intermittent IV infusion, vials labeled as containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone should be reconstituted with 2.4, 4.8, 9.6, or 19.2 mL, respectively, of a compatible IV solution to provide solutions containing approximately 100 mg/mL.1,2 The reconstituted solution should then be further diluted to the desired concentration by withdrawing the entire contents of the vial and adding it to an appropriate IV diluent.1,2 Ceftriaxone solutions for IV infusion containing 10-40 mg/mL are recommended; however, lower concentrations may be used.1,2

Alternatively, ADD-Vantage® vials containing 1 or 2 g of ceftriaxone should be reconstituted with 0.9% sodium chloride or 5% dextrose injection in ADD-Vantage® flexible containers according to the manufacturer's directions and administered by IV infusion.32

Alternatively, the commercially available Duplex® drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection, respectively, in separate chambers should be reconstituted (activated) according to the manufacturer's directions and administered by IV infusion.3 If stored in the refrigerator after reconstitution (see Chemistry and Stability: Stability), the solution should be allowed to reach room temperature prior to administration.3

The 10-g pharmacy bulk package of ceftriaxone is reconstituted by adding 95 mL of a compatible IV solution to provide a solution containing approximately 100 mg/mL.18 Reconstituted solutions in the ceftriaxone pharmacy bulk package should not be used for direct IV infusion; these reconstituted solutions must be further diluted in a compatible IV infusion solution, generally to a concentration of 10-40 mg/mL, although lower concentrations may be used if desired.18

Thawed solutions of the commercially available frozen premixed ceftriaxone sodium injection in dextrose should be administered only by intermittent IV infusion.30 The commercially available frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C);30 the injection should not be thawed by warming in a water bath or by exposure to microwave radiation.30 The container may be fragile in the frozen state and should be handled with care.30 Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature; potency is not affected.30 After thawing at room temperature, the injection should be agitated and the container checked for minute leaks by firmly squeezing the bag.30 The injection should be discarded if container seals or outlet ports are not intact or leaks are found or if the solution is cloudy or contains an insoluble precipitate.30 Additives should not be introduced into the injection container.30 The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.30

Rate of Administration

The manufacturers recommend that intermittent IV infusions of ceftriaxone sodium be infused over 30 minutes (except in neonates).1,2,3,18,30,32

In neonates, the manufacturers recommend that intermittent IV infusions of ceftriaxone be given over 60 minutes.1,2,18,32 (See Cautions: Pediatric Precautions.)

IM Injection

IM injections of ceftriaxone sodium should be prepared by adding 0.9, 1.8, 3.6, or 7.2 mL of compatible diluent (e.g., sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, bacteriostatic water for injection containing 0.9% benzyl alcohol, 1% lidocaine hydrochloride without epinephrine) to vials labeled as containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 250 mg/mL or by adding 1, 2.1, or 4.2 mL of one of these diluents to vials labeled as containing 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 350 mg/mL.1,2 More dilute solutions of the drug may be used for IM injection if required.1,2

Solutions of the drug for IM injection that have been reconstituted with bacteriostatic water containing benzyl alcohol should not be used in neonates.176,177 (See Cautions: Pediatric Precautions.)

IM injections of ceftriaxone should be made deeply into a large muscle mass, using usual techniques and precautions.1,2

Dosage !!navigator!!

Dosage of ceftriaxone sodium is expressed in terms of ceftriaxone1,2,3,18,30,32 and is identical for IM or IV administration.1

To avoid unintentional overdosage, the commercially available Duplex delivery system containing ceftriaxone and dextrose injection should not be used in patients who require less than the entire 1- or 2-g dose in the container.3

Pediatric Dosage

General Pediatric Dosage

The American Academy of Pediatrics (AAP) recommends that neonates 28 days of age or younger receive ceftriaxone in a dosage of 50 mg/kg once daily, regardless of weight.292

For pediatric patients beyond the neonatal period, AAP recommends a ceftriaxone dosage of 50-75 mg/kg once daily for the treatment of mild to moderate infections or a dosage of 100 mg/kg daily given in 1 or 2 doses for the treatment of severe infections.292

The manufacturers state that the usual dosage of ceftriaxone for the treatment of serious infections (other than meningitis) in pediatric patients is 50-75 mg/kg daily given in divided doses every 12 hours.1,2,18,30,32 The maximum dosage recommended by the manufacturers for pediatric patients is 2 g daily.1,2,18,30,32

Endocarditis

For the treatment of native valve endocarditis† caused by streptococci highly susceptible to penicillin (penicillin MIC 0.1 mcg/mL or less), including Streptococcus pyogenes (group A β-hemolytic streptococci; GAS), S. agalactiae (group B streptococci; GBS), streptococci groups C or G, most viridans group streptococci, or nonenterococcal group D streptococci (e.g., S. gallolyticus [formerly S. bovis ], S. equinas ), the American Heart Association (AHA) states that pediatric patients may receive IV ceftriaxone in a dosage of 100 mg/kg daily in divided doses every 12 hours for 4 weeks.452 Alternatively, AHA states that IV ceftriaxone can be given in a dosage of 80 mg/kg once daily (up to 4 g daily), but doses greater than 2 g should be given in divided doses every 12 hours.452

For the treatment of native valve endocarditis† caused by streptococci relatively resistant to penicillin (penicillin MIC greater than 0.1 but less than 0.5 mcg/mL), AHA states that pediatric patients may receive IV ceftriaxone in a dosage of 100 mg/kg daily in divided doses every 12 hours for 4 weeks in conjunction with gentamicin (3-6 mg/kg daily IV in divided doses every 8 hours given concomitantly during the first 2 weeks of ceftriaxone treatment).452 Alternatively, AHA states that IV ceftriaxone can be given in a dosage of 80 mg/kg once daily (up to 4 g daily) in this regimen.452

For the treatment of endocarditis† involving prosthetic valves or other prosthetic material caused by penicillin-susceptible streptococci (penicillin MIC 0.1 mcg/mL or less), AHA states that pediatric patients may receive IV ceftriaxone in a dosage of 100 mg/kg daily in divided doses every 12 hours for 6 weeks in conjunction with gentamicin (3-6 mg/kg daily IV in divided doses every 8 hours given concomitantly during the first 2 weeks of ceftriaxone treatment).452 Alternatively, AHA states that IV ceftriaxone can be given in a dosage of 80 mg/kg once daily (up to 4 g daily) in this regimen.452 If endocarditis involving prosthetic valves or other prosthetic material is caused by streptococci with penicillin MIC greater than 0.1 mcg/mL or caused by Abiotrophia or Granulicatella , AHA recommends that ceftriaxone be given for 6 weeks in conjunction with gentamicin (given concomitantly for the entire 6 weeks of ceftriaxone treatment).452

For the treatment of endocarditis† caused by the HACEK group (i.e., Haemophilus , Aggregatibacter , Cardiobacterium hominis , Eikenella corrodens , Kingella ), AHA states that pediatric patients may receive IV ceftriaxone in a dosage of 100 mg/kg daily in divided doses every 12 hours for 4 weeks.452 Alternatively, AHA states that IV ceftriaxone can be given in a dosage of 80 mg/kg once daily (up to 4 g daily) for 4 weeks.452

GI Infections

If ceftriaxone is used as an alternative for the treatment of Salmonella gastroenteritis† (with or without bacteremia) in adolescents with human immunodeficiency virus (HIV) infection, the US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and Infectious Diseases Society of America (IDSA) recommend a dosage of 1 g IV every 24 hours.440 The recommended duration of treatment is 7-14 days in those with CD4+ T-cell counts of 200 cells/mm3 or greater (14 days or longer if bacteremia is present or the infection is complicated) or 2-6 weeks in those with CD4+ T-cell counts less than 200 cells/mm3.440

For the treatment of shigellosis† caused by Shigella sonnei or S. flexneri , pediatric patients have received ceftriaxone in a dosage of 50 mg/kg once daily for 2-5 days.401,402

If ceftriaxone is used as an alternative for empiric treatment of infectious diarrhea† in HIV-infected adolescents, CDC, NIH, and IDSA recommend a dosage of 1 g IV every 24 hours.440 If there is no clinical response after 5-7 days, stool culture and in vitro susceptibility testing should be considered.440

Intra-abdominal Infections

If ceftriaxone is used for empiric treatment of complicated intra-abdominal infections in pediatric patients, a dosage of 50-75 mg/kg once or twice daily is recommended.708 Although ceftriaxone may be used alone for initial empiric treatment of community-acquired biliary tract infections (cholecystitis or cholangitis), the drug should be used in conjunction with metronidazole for initial empiric treatment of extrabiliary community-acquired intra-abdominal infections.708

Meningitis and Other CNS Infections

For the treatment of meningitis caused by susceptible bacteria, the manufacturers and some clinicians recommend that pediatric patients receive an initial ceftriaxone dosage of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily (up to 4 g daily) given once daily or in equally divided doses every 12 hours for 7-21 days.1,2,3,18,30,32,123,130,140,142,143,187,243,292 Other clinicians recommend a dosage of 80-100 mg/kg daily (up to 4 g daily) given once daily or in divided doses every 12 hours.245,249,250,259,418,471 A twice-daily dosing regimen may be preferred for the treatment of meningitis caused by S. pneumoniae .292

While 7 days of anti-infective therapy may be adequate for the treatment of uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis , at least 10-14 days of therapy is suggested for complicated cases or meningitis caused by S. pneumoniae and at least 21 days is suggested for meningitis caused by susceptible Enterobacteriaceae† (e.g., Escherichia coli , Klebsiella †).418,475 In neonates, some experts state that treatment of meningitis should be continued for 2 weeks beyond the first sterile CSF culture or for at least 3 weeks, whichever is longer.418

If IV ceftriaxone is used for the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible bacteria (see Uses: Meningitis and Other CNS Infections), IDSA recommends that infants and children receive a dosage of 100 mg/kg daily as a single dose or in divided doses every 12 hours.416 The duration of treatment depends on the causative organism and patient characteristics.416 The recommended treatment duration is 10-14 days for infections caused by gram-negative bacilli (with or without significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features);416 some experts recommend a duration of 21 days.416

Respiratory Tract Infections

If ceftriaxone is used in children for the treatment of severe acute bacterial rhinosinusitis† requiring hospitalization, IDSA recommends a dosage of 50 mg/kg daily given IV in divided doses every 12 hours.728

For the treatment of community-acquired pneumonia (CAP) caused by S. pneumoniae in pediatric patients 3 months of age or older, IDSA recommends that ceftriaxone be given in a dosage of 50-100 mg/kg daily as a single dose or in divided doses every 12 hours if the infection is caused by penicillin-susceptible strains or a dosage of 100 mg/kg daily as a single dose or in divided doses every 12 hours if the infection is caused by penicillin-resistant strains.513 Treatment usually is continued for 10 days.513

For the treatment of CAP caused by susceptible S. pyogenes (group A β-hemolytic streptococci; GAS) or H. influenzae in pediatric patients 3 months of age or older, IDSA recommends that ceftriaxone be given in a dosage of 50-100 mg/kg daily as a single daily dose or in divided doses every 12 hours.513 Treatment usually is continued for 10 days.513

Skin and Skin Structure Infections

The usual dosage of ceftriaxone for the treatment of skin and skin structure infections caused by susceptible organisms in pediatric patients is 50-75 mg/kg daily given as a single daily dose or in equally divided doses every 12 hours.1,18,30,32,59,123,124,130,32

Acute Otitis Media

For the treatment of acute otitis media (AOM), the manufacturers recommend that pediatric patients receive a single 50-mg/kg IM dose of ceftriaxone (maximum dose 1 g).1,2

For initial treatment of AOM, AAP recommends a ceftriaxone dosage of 50 mg/kg daily given IM or IV for 1 to 3 days†.683 AAP cautions that more than a single dose may be required to prevent recurrence.683

For retreatment in patients with AOM who failed to respond to an initial anti-infective regimen, AAP recommends a ceftriaxone dosage of 50 mg/kg daily given for 3 days†.683

Chancroid

When ceftriaxone is used for the treatment of chancroid† (genital ulcers caused by H. ducreyi ), AAP recommends that infants and children weighing less than 45 kg receive a single 50-mg/kg IM dose (up to 250 mg) and that pediatric patients weighing 45 kg or more receive a single 250-mg IM dose.292

Gonococcal Infections in Neonates

When ceftriaxone is used for parenteral prophylaxis † or presumptive treatment of gonorrhea† in neonates born to mothers with gonorrhea, CDC and AAP recommend that a single dose of 25-50 mg/kg (maximum 125 mg) of the drug be given IM or IV at birth.292,344

For the treatment of gonococcal ophthalmia neonatorum†, CDC and AAP recommend that neonates receive a single IM or IV dose of 25-50 mg/kg (maximum 125 mg) of ceftriaxone.292,344

For the treatment of disseminated gonococcal infections (e.g., sepsis, arthritis, meningitis) or gonococcal scalp abscess in neonates†, the usual dosage of ceftriaxone is 25-50 mg/kg IM or IV once daily for 7 days.292,344 If meningitis is documented, ceftriaxone should be continued for 10-14 days.292,344

Gonococcal Infections in Infants and Children

For the treatment of uncomplicated gonorrhea in children beyond the neonatal age (prepubertal), AAP recommends that those weighing less than 45 kg receive a single 125-mg IM dose of ceftriaxone and that those weighing 45 kg or more receive a single 250-mg IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose).292 CDC recommends that infants and children with uncomplicated gonococcal infections (vulvovaginitis, cervicitis, urethritis, pharyngitis, proctitis) weighing 45 kg or less receive a single IV or IM ceftriaxone dose of 25-50 mg/kg (up to 125 mg IM) and that those weighing more than 45 kg receive a single 250-mg IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose).344

For the treatment of disseminated or complicated gonococcal infections† (e.g., arthritis-dermatitis syndrome) in children beyond the neonatal period (prepubertal), AAP recommends that those weighing less than 45 kg receive IV or IM ceftriaxone in a dosage of 50 mg/kg once daily (up to 1 g daily) for 7 days in conjunction with erythromycin (30 mg/kg daily given orally in 4 divided doses [up to 2 g daily] for 14 days) and that those weighing 45 kg or more receive IV or IM ceftriaxone in a dosage of 1 g once daily for 7 days in conjunction with a dose of azithromycin (single 1-g oral dose).292 If meningitis or endocarditis is present, AAP recommends that dosage and duration of ceftriaxone in these regimens be increased to 50 mg/kg IV or IM every 12-24 hours for 10-14 days in those weighing less than 45 kg or 1-2 g IV every 12-24 hours for 10-14 days in those weighing 45 kg or more.292

For the treatment of gonococcal bacteremia or arthritis in children, CDC recommends that those weighing 45 kg or less receiving IM or IV ceftriaxone in a dosage of 50 mg/kg daily (maximum 1 g daily) for 7 days and that those weighing more than 45 kg receive an IM or IV ceftriaxone dosage of 1 g once daily for 7 days.344

Gonorrhea and Associated Infections in Adolescents

For the treatment of uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea, CDC recommends that adolescents receive a single 250-mg IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose).344

For the treatment of gonococcal conjunctivitis†, adolescents should receive a single 1-g IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose).344

For the treatment of gonococcal arthritis and arthritis-dermatitis syndrome†, CDC recommends that adolescents receive 1 g of ceftriaxone IV or IM once daily and a dose of azithromycin (single 1-g oral dose).344 Ceftriaxone should be continued until 24-48 hours after substantial clinical improvement; treatment can then be switched to an oral antibacterial selected based on in vitro susceptibility testing and given to complete a total treatment duration of at least 7 days.344

For the treatment of gonococcal meningitis† or gonococcal endocarditis†, CDC recommends that adolescents receive 1-2 g of ceftriaxone IV every 12-24 hours and a dose of azithromycin (single 1-g oral dose).344 Ceftriaxone should be continued for 10-14 days in those with meningitis and for at least 4 weeks in those with endocarditis.344

Prophylaxis in Sexual Assault Victims

For empiric anti-infective prophylaxis for gonorrhea, chlamydia, and trichomoniasis in adolescent sexual assault victims†, CDC recommends that a single 250-mg IM dose of ceftriaxone be given in conjunction with azithromycin (single 1-g oral dose) and either metronidazole (single 2-g oral dose) or tinidazole (single 2-g oral dose).344

Lyme Disease

If IV ceftriaxone is used for the treatment of early Lyme disease† in children with acute neurologic disease manifested by meningitis or radiculopathy, IDSA and AAP recommend a dosage of 50-75 mg/kg (up to 2 g) once daily for 14 days (range: 10-28 days).292,329

When a parenteral regimen is indicated for the treatment of Lyme carditis† in patients with atrioventricular (AV) heart block and/or myopericarditis associated with early Lyme disease, IDSA recommends that children receive IV ceftriaxone in a dosage of 50-75 mg/kg (up to 2 g) once daily for 14 days (range: 14-21 days).329 Although a parenteral regimen is recommended for initial treatment of hospitalized patients, the parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy and for outpatients.329

When a parenteral regimen is indicated for the treatment of Lyme arthritis† in patients with evidence of neurologic disease or when arthritis has not responded to an oral regimen, IDSA and AAP recommend that children receive IV ceftriaxone in a dosage of 50-75 mg/kg (up to 2 g) once daily for 14 days (range: 14-28 days).292,329

For the treatment of late neurologic Lyme disease† affecting the central or peripheral nervous system, IDSA and AAP recommend that children receive IV ceftriaxone in a dosage of 50-75 mg/kg (up to 2 g) once daily for 2-4 weeks.292,329

Neisseria meningitidis Infections

When ceftriaxone is used to eliminate nasopharyngeal carriage of N. meningitidis † or for chemoprophylaxis in close contacts of individuals with invasive meningococcal disease†, a single 125-mg IM dose should be used in children and adolescents younger than 15 years of age and a single 250-mg IM dose should be used in adolescents 15 years of age or older.292,376

For dosage recommendations for the treatment of meningitis caused by N. meningitidis , see Meningitis and Other CNS Infections under Dosage: Pediatric Dosage, in Dosage and Administration.)

Pelvic Inflammatory Disease

For the treatment of mild to moderately severe acute pelvic inflammatory disease (PID) when an IM and oral regimen is indicated, adolescents may receive a single 250-mg IM dose of ceftriaxone followed by a 14-day regimen of doxycycline (100 mg orally twice daily) with or without metronidazole (500 mg orally twice daily).344,345 If there is no clinical response within 72 hours, the patient should be reevaluated to confirm the diagnosis and an IV regimen should be administered if indicated.344

Syphilis

If ceftriaxone is used as an alternative in infants or children with clinical evidence of congenital syphilis† when penicillin G is not available, dosage should be based on age and weight.344 CDC states that infants 30 days of age or older may receive a dosage of 75 mg/kg IV or IM once daily for 10-14 days (dosage adjustments may be needed based on weight) and children may receive 100 mg/kg IV or IM once daily for 10-14 days.344 Clinicians should consider that ceftriaxone is contraindicated in certain neonates (see Cautions: Pediatric Precautions).344 Ceftriaxone should be used for the treatment of congenital syphilis only when necessary (i.e., during a penicillin shortage) and should be used in consultation with a specialist in the treatment of infants with congenital syphilis and with close clinical, serologic, and CSF follow-up.344

If ceftriaxone is used as an alternative to IM penicillin G benzathine for the treatment of primary or secondary syphilis† in penicillin-allergic nonpregnant adolescents, CDC and other clinicians recommend a ceftriaxone dosage of 1-2 g IM or IV once daily for 10-14 days.344,345,350,440 Some clinicians suggest that this ceftriaxone dosage also can be used as an alternative in penicillin-allergic nonpregnant adolescents with early latent syphilis.345,350,440

If ceftriaxone is used as an alternative to IV penicillin G for the treatment of neurosyphilis† in penicillin-allergic nonpregnant adolescents, CDC and others suggest a dosage of 2 g IM or IV daily for 10-14 days based on limited data.344,440

CDC cautions that the optimal dosage and duration of ceftriaxone for the treatment of syphilis have not been defined and close follow-up is essential.344 (See Uses: Syphilis.)

Typhoid Fever and Other Invasive Salmonella Infections

For the treatment of typhoid fever† (enteric fever) or septicemia caused by Salmonella serovar Typhi†, including multidrug-resistant strains, pediatric patients have received ceftriaxone in a dosage of 50-75 mg/kg given IM or IV once daily.167,407,408,409 While ceftriaxone has been effective for the treatment of typhoid fever when administered for 3-7 days,167,406,407,409,410 anti-infective therapy for the treatment of typhoid fever usually is continued for at least 14 days to prevent relapse292,404,408 and a duration of at least 4-6 weeks may be necessary for the treatment of immunocompromised individuals (including HIV-infected individuals) or for the treatment of Salmonella meningitis.292

Empiric Therapy in Febrile Neutropenic Patients

When used for empiric anti-infective therapy in febrile neutropenic patients†, children have received ceftriaxone in a dosage of 80 mg/kg (up to 2 g) once daily in conjunction with amikacin (20 mg/kg IV daily).387,388

Prevention of Bacterial Endocarditis

If ceftriaxone is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals with certain cardiac conditions who are undergoing certain dental or upper respiratory tract procedures (see Uses: Prevention of Bacterial Endocarditis), AHA recommends that children receive a single dose of 50 mg/kg given IV or IM 30-60 minutes prior to the procedure.451

Adult Dosage

General Adult Dosage

The usual adult dosage of ceftriaxone for the treatment of most infections caused by susceptible organisms is 1-2 g given once daily or in equally divided doses twice daily, depending on the type and severity of the infection.1,2,3,18,30,32,87,89,91,104,119,120,125,127,128,129,131

One manufacturer recommends that adults receive ceftriaxone in a dosage of 50-75 mg/kg every 12 hours (maximum 2 g daily) for the treatment of serious infections other than meningitis.3

The maximum adult dosage of ceftriaxone recommended by the manufacturers is 4 g daily.1,2,3,18,30,32

Bone and Joint Infections

For the treatment of native vertebral osteomyelitis caused by susceptible staphylococci, β-hemolytic streptococci†, or Cutibacterium acnes † (formerly Propionibacterium acnes ), IDSA recommends that adults receive ceftriaxone in a dosage of 2 g IV once daily for 6 weeks.590

If ceftriaxone is used as an alternative for the treatment of native vertebral osteomyelitis caused by susceptible Salmonella † (nalidixic acid-resistant strains), IDSA recommends that adults receive a dosage of 2 g IV once daily for 6-8 weeks.590

For the treatment of prosthetic joint infections caused by susceptible staphylococci, IDSA recommends that adults receive ceftriaxone in a dosage of 1-2 g IV once daily for 2-4 weeks in conjunction with rifampin (300-450 mg orally twice daily) and that this regimen be followed by an oral anti-infective regimen (e.g., rifampin and ciprofloxacin or levofloxacin) to complete a total treatment duration of 3 months for infections related to total hip arthroplasty or 6 months for infections related to total knee arthroplasty.591

For the treatment of prosthetic joint infections caused by susceptible β-hemolytic streptococci or C. acnes †, IDSA recommends that adults receive 2 g IV once daily for 4-6 weeks.591

Endocarditis

For the treatment of native valve endocarditis† caused by viridans group streptococci or S. gallolyticus highly susceptible to penicillin (penicillin MIC 0.12 mcg/mL or less), AHA recommends that adults receive IV or IM ceftriaxone in a dosage of 2 g once daily for 4 weeks.450 Alternatively, adults with uncomplicated endocarditis† caused by highly penicillin-susceptible viridans group streptococci or S. gallolyticus who are at low risk for adverse effects related to aminoglycoside therapy may receive a 2-week regimen consisting of IV or IM ceftriaxone in a dosage of 2 g once daily in conjunction with gentamicin (3 mg/kg daily IV or IM given as a single daily dose or as 1 mg/kg every 8 hours).450 The 2-week regimen is not recommended for patients with known cardiac or extracardiac abscesses, creatinine clearance less than 20 mL/minute, impaired eighth cranial nerve function, or infection with Abiotrophia , Granulicatella , or Gemella .450

For the treatment of endocarditis† involving prosthetic valves or other prosthetic material caused by viridans group streptococci or S. gallolyticus highly susceptible to penicillin (penicillin MIC 0.12 mcg/mL or less), AHA states that adults can receive IV or IM ceftriaxone in a dosage of 2 g once daily for 6 weeks with or without gentamicin (3 mg/kg daily IV or IM as a single daily dose or as 1 mg/kg every 8 hours given concomitantly during the first 2 weeks of ceftriaxone treatment).450 When endocarditis involving prosthetic valves or other prosthetic material is caused by viridans group streptococci or S. gallolyticus relatively or highly resistant to penicillin (penicillin MIC greater than 0.12 mcg/mL), AHA states that it is reasonable to extend the duration of concomitant gentamicin to the entire 6 weeks of ceftriaxone treatment.450

When a double β-lactam regimen is used for the treatment of enterococcal endocarditis† involving native valves or prosthetic valves or other prosthetic material (see Enterococcal Endocarditis under Uses: Endocarditis), AHA recommends that adults receive ceftriaxone in a dosage of 2 g IV every 12 hours in conjunction with ampicillin (2 g IV every 4 hours).450 Both drugs should be continued for 6 weeks.450

For the treatment of endocarditis† caused by the HACEK group (i.e., Haemophilus , Aggregatibacter , C. hominis , E. corrodens , Kingella ), AHA recommends that adults receive IV or IM ceftriaxone in a dosage of 2 g once daily.450 A duration of 4 weeks is reasonable for the treatment of native valve endocarditis and 6 weeks is reasonable for the treatment of endocarditis involving prosthetic valves or other prosthetic material.450

GI Infections

If ceftriaxone is used as an alternative for the treatment of Salmonella gastroenteritis† (with or without bacteremia) in HIV-infected adults, CDC, NIH, and IDSA recommend a dosage of 1 g IV every 24 hours.440 The recommended duration of treatment is 7-14 days in those with CD4+ T-cell counts of 200 cells/mm3 or greater (14 days or longer if the patient is bacteremic or the infection is complicated) or 2-6 weeks in those with CD4+ T-cell counts less than 200 cells/mm3.440

If ceftriaxone is used as an alternative for empiric treatment of infectious diarrhea† in HIV-infected adults, CDC, NIH, and IDSA recommend a dosage of 1 g IV every 24 hours.440 If there is no clinical response after 5-7 days, stool culture and in vitro susceptibility testing should be considered.440

Intra-abdominal Infections

If ceftriaxone is used for empiric treatment of complicated intra-abdominal infections, a dosage of 1-2 g once or twice daily is recommended.708 Although ceftriaxone may be used alone for initial empiric treatment of community-acquired biliary tract infections (cholecystitis or cholangitis), the drug should be used in conjunction with metronidazole for initial empiric treatment of extrabiliary community-acquired intra-abdominal infections.708

Meningitis and Other CNS Infections

For the treatment of meningitis caused by susceptible bacteria, the usual adult dosage of ceftriaxone is 2 g IV every 12 hours.179,418,475 Some manufacturers and clinicians suggest a ceftriaxone dosage of 50-100 mg/kg (up to 4 g) once daily or in 2 equally divided doses every 12 hours;3,473 some clinicians suggest a dosage of 4 g daily given in 1 or 2 equally divided doses.418

While 7 days of anti-infective therapy may be adequate for the treatment of uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis , at least 10-14 days of therapy is suggested for complicated cases or meningitis caused by S. pneumoniae and at least 21 days of therapy is suggested for meningitis caused by susceptible Enterobacteriaceae† (e.g., E. coli , Klebsiella †).418,475

If ceftriaxone is used for the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible bacteria (see Uses: Meningitis and Other CNS Infections), IDSA recommends that adults receive a dosage of 4 g daily given in divided doses every 12 hours.416 The duration of treatment depends on the causative organism and patient characteristics.416 The recommended treatment duration is 10-14 days for infections caused by gram-negative bacilli (with or without significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features);416 some experts recommend a duration of 21 days.416

Respiratory Tract Infections

If ceftriaxone is used for the treatment of severe acute bacterial rhinosinusitis† requiring hospitalization, IDSA recommends that adults receive a dosage of 1-2 g IV every 12-24 hours.728

Skin and Skin Structure Infections

For the treatment of skin and skin structure infections, adults should receive ceftriaxone in a dosage of 50-75 mg/kg once daily or in 2 equally divided doses every 12 hours (maximum 2 g daily).3

If ceftriaxone is used for the treatment of necrotizing fasciitis involving Aeromonas hydrophila †, IDSA recommends that adults receive a dosage of 1-2 g IV once daily in conjunction with doxycycline (100 mg IV every 12 hours).543 If necrotizing fasciitis involves Vibrio vulnificus †, IDSA recommends that adults receive ceftriaxone in a dosage of 1 g IV once daily in conjunction with doxycycline (100 mg IV every 12 hours).543

If ceftriaxone is used for the treatment of surgical site infections following intestinal or genitourinary tract surgery, IDSA recommends a dosage of 1 g once daily in conjunction with metronidazole (500 mg IV every 8 hours).543 For the treatment of surgical site infections following procedures involving the axilla or perineum, IDSA recommends that ceftriaxone be given in a dosage of 1 g once daily;543 concomitant vancomycin (15 mg/kg every 12 hours) may also be needed.543

If ceftriaxone is used for the treatment of an infected animal bite wound, IDSA recommends a dosage of 1 g IV every 12 hours.543

Urinary Tract Infections

For the treatment of acute pyelonephritis (e.g., pending results of in vitro susceptibility testing), a single 1-g IV dose of ceftriaxone has been recommended followed by an appropriate oral anti-infective regimen given for 7-14 days.743

Chancroid

If ceftriaxone is used for the treatment of chancroid† (genital ulcers caused by H. ducreyi ), CDC and other clinicians recommend that adults receive a single 250-mg IM dose of the drug.344,345

Gonorrhea and Associated Infections

For the treatment of uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea, adults should receive a single 250-mg IM dose of ceftriaxone1,2,344,345 and a dose of azithromycin (single 1-g oral dose).344 (See Gonococcal Infections in Adults and Adolescents in Uses: Gonorrhea and Associated Infections.)

For the treatment of gonococcal conjunctivitis†, adults should receive a single 1-g IM dose of ceftriaxone and a dose of azithromycin (single 1-g oral dose).344

For the treatment of gonococcal arthritis and arthritis-dermatitis syndrome†, CDC recommends that adults receive 1 g of ceftriaxone IV or IM once daily and a dose of azithromycin (single 1-g oral dose).344 Ceftriaxone should be continued until 24-48 hours after substantial clinical improvement; treatment can then be switched to an oral antibacterial (selected based on in vitro susceptibility testing) to complete a total treatment duration of at least 7 days.344

For the treatment of gonococcal meningitis† or gonococcal endocarditis†, CDC recommends that adults receive 1-2 g of ceftriaxone IV every 12-24 hours in conjunction with a dose of azithromycin (single 1-g oral dose).344 Ceftriaxone should be continued for 10-14 days in those with meningitis and for at least 4 weeks in those with endocarditis.344

For presumptive treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea†, adults should receive a single 250-mg IM dose of ceftriaxone given in conjunction with doxycycline (100 mg orally twice daily for 10 days).344

For presumptive treatment of acute epididymitis most likely caused by sexually transmitted chlamydia, gonorrhea, and enteric bacteria† (e.g., E. coli ), adults should receive a single 250-mg IM dose of ceftriaxone given in conjunction with levofloxacin (500 mg orally once daily for 10 days) or ofloxacin (300 mg orally twice daily for 10 days).344

For presumptive treatment of acute proctitis†, adults should receive a single 250-mg IM dose of ceftriaxone given in conjunction with doxycycline (100 mg orally twice daily for 7 days).344

Prophylaxis in Sexual Assault Victims

For empiric anti-infective prophylaxis for gonorrhea, chlamydia, and trichomoniasis in adult sexual assault victims†, CDC recommends that a single 250-mg IM dose of ceftriaxone be given in conjunction with azithromycin (single 1-g oral dose) and either metronidazole (single 2-g oral dose) or tinidazole (single 2-g oral dose).344

Leptospirosis

For the treatment of severe leptospirosis†, adults have received ceftriaxone in a dosage of 1 g IV once daily for 7 days.690

Lyme Disease

If ceftriaxone is used for the treatment of early Lyme disease† in adults with acute neurologic disease manifested by meningitis or radiculopathy, IDSA and other clinicians recommend a dosage of 2 g IV once daily for 14 days (range: 10-28 days).329

When a parenteral regimen is indicated for the treatment of Lyme carditis† in adults with AV heart block and/or myopericarditis associated with early Lyme disease, IDSA and other clinicians recommend a ceftriaxone dosage of 2 g IV once daily for 14 days (range: 14-21 days).279,290,292,329,357,359,361,362,366,497 Although a parenteral regimen is recommended for initial treatment of hospitalized patients, the parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy and for outpatients.329

When a parenteral regimen is indicated for the treatment of Lyme arthritis† in patients with evidence of neurologic disease or when arthritis has not responded to an oral regimen, IDSA and other clinicians recommend that adults receive a ceftriaxone dosage of 2 g IV once daily for 14 days (range: 14-28 days).279,290,292,329,357,359,361,362,366,497

For the treatment of late neurologic Lyme disease† affecting the central or peripheral nervous system, IDSA and other clinicians recommend that adults receive ceftriaxone in a dosage of 2 g IV once daily for 2-4 weeks.279,290,292,329,357,359,361,362,366,497

Neisseria meningitidis Infections

When ceftriaxone is used to eliminate nasopharyngeal carriage of N. meningitidis † or for chemoprophylaxis in close contacts of individuals with invasive meningococcal disease†, adults should receive a single 250-mg IM dose.376

For dosage recommendations for the treatment of meningitis caused by N. meningitidis , see Meningitis and Other CNS Infections under Dosage: Adult Dosage, in Dosage and Administration.)

Pelvic Inflammatory Disease

For the treatment of mild to moderately severe acute pelvic inflammatory disease (PID) when an IM and oral regimen is indicated, adults may receive a single 250-mg IM dose of ceftriaxone followed by a 14-day regimen of doxycycline (100 mg orally twice daily) with or without oral metronidazole (500 mg twice daily).344,345 If there is no clinical response within 72 hours, the patient should be reevaluated to confirm the diagnosis and an IV regimen should be administered if indicated.344

Syphilis

If ceftriaxone is used as an alternative to IM penicillin G benzathine for the treatment of primary or secondary syphilis† in penicillin-allergic nonpregnant adults, CDC and other clinicians recommend a ceftriaxone dosage of 1-2 g IM or IV once daily for 10-14 days.344,345,350,440 Some clinicians suggest that this ceftriaxone dosage also can be used as an alternative in penicillin-allergic nonpregnant adults with early latent syphilis.345,350,440

If ceftriaxone is used as an alternative to IV penicillin G for the treatment of neurosyphilis† in penicillin-allergic nonpregnant adults, a dosage of 2 g IM or IV daily for 10-14 days has been suggested by CDC and others based on limited data.344,440

CDC cautions that the optimal dosage and duration of ceftriaxone for the treatment of syphilis have not been defined and close follow-up is essential.344 (See Uses: Syphilis.)

Typhoid Fever and Other Invasive Salmonella Infections

For the treatment of typhoid fever† or septicemia caused by Salmonella serovars Typhi† or Paratyphi†, including infections caused by multidrug-resistant strains, adults have received ceftriaxone in a dosage of 2-4 g IM or IV once daily for 3-7 days.167,407,410 Alternatively, adults have received a dosage of 1 g once daily for 15 days.404,407

While ceftriaxone has been effective for the treatment of typhoid fever when administered for 3-7 days,167,406,407,409,410 anti-infective therapy for the treatment of typhoid fever usually is continued for at least 14 days to prevent relapse292,404,408 and a duration of at least 4-6 weeks may be necessary for the treatment of immunocompromised individuals (including those with HIV infection) or for the treatment of Salmonella meningitis.292

Whipple's Disease

For the treatment of Whipple's disease† caused by Tropheryma whipplei (formerly Tropheryma whippelii ), some clinicians recommend that ceftriaxone be given in a dosage of 2 g IV once daily for 2-4 weeks followed by oral co-trimoxazole given for 1-2 years.730,731,732 For the treatment of encephalitis caused by T. whipplei , IDSA recommends initial treatment with ceftriaxone given for 2-4 weeks followed by co-trimoxazole or cefixime for 1-2 years.506

Empiric Therapy in Febrile Neutropenic Patients

When used for empiric anti-infective therapy in febrile neutropenic patients†, adults have received ceftriaxone in a dosage of 30 mg/kg (up to 2 g) given IV once daily in conjunction with amikacin (20 mg/kg IV once daily).388,437

Perioperative Prophylaxis

If ceftriaxone is used for perioperative prophylaxis in adults, the manufacturers and some clinicians recommend that a single 1-g dose be given IV 0.5-2 hours prior to surgery.1,2,3,18,30,32,148,151,152,154,155

For perioperative prophylaxis in patients undergoing cholecystectomy, adults have received a single 1-g dose of ceftriaxone given IV 0.5-2 hours prior to surgery;192,294,295,298 however, higher doses (e.g., 2 g) also have been used.192,296,297

For perioperative prophylaxis in adults undergoing colorectal procedures, some experts recommend that a single 2-g dose of ceftriaxone be given IV in conjunction with metronidazole (single 500-mg IV dose) within 1 hour prior to surgery.360,374

Prevention of Bacterial Endocarditis

If ceftriaxone is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals with certain cardiac conditions who are undergoing certain dental or upper respiratory tract procedures (see Uses: Prevention of Bacterial Endocarditis), AHA recommends that adults receive a single dose of 1 g given IM or IV 30-60 minutes prior to the procedure.451

Dosage in Renal and Hepatic Impairment !!navigator!!

Modification of the usual dosage of ceftriaxone is not usually necessary in adults with impaired renal or hepatic function alone who are receiving the drug in dosages up to 2 g daily.1,2,3,18,30,32,73,77,84,85,104,105,107,170 However, if the drug is used in patients with hepatic impairment and clinically important renal impairment, caution is advised and dosage should not exceed 2 g daily.1,2,3,18,30,32

Some clinicians state that serum concentrations of the drug should be monitored when ceftriaxone is used in patients with severe renal impairment (e.g., dialysis patients) or in patients with both hepatic and substantial renal impairment.73,74,77,170

Because ceftriaxone is not removed by hemodialysis or peritoneal dialysis, supplemental doses of the drug are unnecessary during or after dialysis.1,2,73,77

Cautions ⬆ ⬇

[Section Outline]

Adverse effects reported with ceftriaxone are similar to those reported with other cephalosporins.1,104,105,106 For information on adverse effects reported with cephalosporins, see Cautions in the Cephalosporins General Statement 8:12.06. Ceftriaxone generally is well tolerated;1 adverse effects have been reported in about 10% of patients receiving ceftriaxone and have required discontinuance of the drug in less than 2% of these patients.104

Hematologic Effects !!navigator!!

Hematologic effects are among the most frequent adverse effects reported with ceftriaxone.93,104 Eosinophilia1,2,18,32,88,93,120,121,125,128,132,140 has been reported in about 6%,1,2,18,32,93 thrombocytosis1,2,18,32,88,91,93,121,128,132 in about 5%,1,2,18,32,93 and leukopenia1,2,3,18,32,91,121,125,128,132 in about 2% of patients receiving ceftriaxone.1,2,18,32,93 Anemia,1,2,18,32,91 neutropenia,1,2,3,18,32,88,140 lymphopenia,1,2,18,32 and thrombocytopenia1,2,3,18,32,91,93,121,132 have been reported in less than 1%1,2,18,32 and leukocytosis, lymphocytosis, monocytosis, agranulocytosis, basophilia, and coagulopathy have been reported in less than 0.1% of patients receiving ceftriaxone.1,2,18,32

Hypoprothrombinemia or prolongation of prothrombin time (PT), with or without bleeding,1,2,18,30,32,95,104,215 has been reported in patients receiving ceftriaxone. (See Other Precautions and Contraindications under Cautions: Precautions and Contraindications.) Although very high concentrations of ceftriaxone (3-4 g/L) inhibited platelet aggregation in an in vitro study,104 in vivo studies indicate that the drug does not interfere with platelet function.179

Immune-mediated hemolytic anemia has been reported in patients receiving ceftriaxone.1,2,3,18,30,32 Severe cases of hemolytic anemia, including fatalities, have occurred in both adults and children.1,2,3,18,30,32,338,339,626 Some cases occurred shortly after administration of a ceftriaxone dose, and some reactions have consisted of severe intravascular hemolysis and anemia, decreased hemoglobin concentrations, reticulocytosis, hemoglobinuria, and cardiac arrest.338,339,626 In at least one case, the direct antiglobulin (Coombs') test was strongly positive and the patient's serum agglutinated washed erythrocytes in the presence of complement and ceftriaxone.338,339 (See Other Precautions and Contraindications under Cautions: Precautions and Contraindications.)

GI Effects !!navigator!!

Diarrhea or loose stools1,2,18,32,56,88,91,92,120,121,125,131,132,140,143 has generally been reported in 2-4% of patients receiving ceftriaxone.1,2,18,32,92,104 However, transient diarrhea was reported in 42-44% of children receiving ceftriaxone in 2 studies122,187 and in 28% (10/36) of adults receiving the drug in another study.104 Nausea,1,2,18,32,92,125 vomiting,1,2,18,32,92 and dysgeusia1,2,18,32 have been reported in less than 1%1,2,18,32 and abdominal pain,92 flatulence,1,2,18,32,92 dyspepsia,1,2,18,32,92 colitis,1,2,18,32,92,121 gallbladder sludge,1,2,18,32 and biliary lithiasis1,2,18,32 have been reported in less than 0.1% of patients receiving the drug.1,2,18,32 Stomatitis and glossitis also have been reported.1,2,3,18,30,32

Pancreatitis, possibly secondary to biliary obstruction, has been reported in patients treated with ceftriaxone.1,2,3,18,30,32 Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition).1,2,3,18,30,32 A cofactor role of ceftriaxone-related biliary precipitation cannot be ruled out.1,2,3,18,30,32

Clostridium difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters the normal colon flora and may permit overgrowth of Clostridium difficile .1,2,3,18,30,32,302,303,304,305,328

C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis.1,2,3,18,30,32,302,303,304,305,328C. difficile produces toxins A and B, which contribute to the development of CDAD;1,2,3,18,30,32,303,304 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since these infections may be refractory to anti-infective therapy and may require colectomy.1,2,3,18,30,32

CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy.1,2,3,18,30,32,302,303,304,305,328 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1,2,3,18,30,32

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued as soon as possible.1,2,3,18,30,32,302,304,305,328 Patients should be managed with appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.1,2,3,18,30,32,302,303,304,305,328 (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions: Precautions and Contraindications.)

Gallbladder Pseudolithiasis

Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving ceftriaxone.1,2,3,18,30,32,209,247,248,255 These precipitates appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones.1,2,3,18,30,32 Although patients may be asymptomatic,1,2,3,18,30,32,209,248,317 symptoms of gallbladder disease (e.g., colic, nausea, vomiting, anorexia) can occur1,2,3,18,30,32,247,248,255,308,309 and may be severe enough to require discontinuance of ceftriaxone therapy.247,248,255,308,309

The condition appears to be reversible and generally resolves following discontinuance of the drug and conservative management;1,2,3,18,30,32,209,247,248,255,308 surgery may not be necessary.247,248,308 The time to resolution, however, is variable and may range from a few days to several months.209,248,255,308,309 Upper abdominal ultrasonography should be considered for patients who develop biliary colic while receiving ceftriaxone therapy; biliary precipitates of ceftriaxone may be detected by ultrasonography after only 4 days of ceftriaxone therapy.315 The risk of precipitation may depend on the dose and rate of IV administration of ceftriaxone, occurring more frequently with relatively high dosages and rapid (e.g., over several minutes) rates of administration.206,247,248,316 In some patients with renal impairment or those receiving higher than usual dosages of the drug, precipitates containing traces of ceftriaxone,248,308 possibly combined with calcium,209 have been recovered in surgical specimens.

The probability of gallbladder precipitates associated with ceftriaxone therapy appears to be greatest in pediatric patients.1,2,3,18,32 In one study in children with various infections who received IV ceftriaxone in a dosage of 60-100 mg/kg daily, gallbladder precipitates developed in 43% of patients.248 The typical abnormality observed sonographically in these children was a strikingly hyperechogenic material with postacoustic shadowing; the precipitates differed from typical biliary sludge or cholelithiasis, usually were mobile, and tended to clump in the most dependent part of the gallbladder.248

In a retrospective study of more than 1300 patients admitted to the hospital during a 2-year period with a diagnosis of Lyme disease, biliary symptoms (e.g., cholecystitis, cholelithiasis) or cholecystectomy occurred in approximately 2% of patients (84% were female with a median age of 12 years [range: 3-40 years]);315,369,372,373 56% of these patients underwent laparoscopic cholecystectomy, mainly for cholelithiasis.315,369 Among cases and controls who received anti-infective therapy for treatment of suspected Lyme disease, each patient had received a median of 3 courses of oral and/or IV anti-infectives.315,369 All patients with biliary symptoms had received IV ceftriaxone therapy within 90 days prior to the occurrence of biliary disease; daily ceftriaxone dosage at the time of onset of biliary symptoms in these patients averaged 57 mg/kg (range: 27-96 mg/kg), and the median duration of therapy was 28 days (range: 4-170 days).315,369 These data suggest an association between biliary complications and the repeated and often prolonged courses of IV ceftriaxone therapy used in these patients, most of whom lacked documented objective clinical or laboratory evidence of Lyme disease.315,369,371 (See Lyme Disease in Uses: Spirochetal Infections.)

In studies in dogs and baboons receiving high dosages of ceftriaxone sodium, concretions consisting of the precipitated calcium salt of ceftriaxone have been found in gallbladder bile.1,2,3,18,32,247,248 These appeared as gritty sediment in dogs who received ceftriaxone in a dosage of 100 mg/kg daily for 4 weeks but were evident in the baboon only after a daily dosage of 335 mg/kg or more for 6 months.1,2,3,18,32 The likelihood of this occurrence in humans has been considered to be low since ceftriaxone has a longer plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile, and the calcium content of human gallbladder bile is relatively low.1,2,18,32

Dermatologic and Sensitivity Reactions !!navigator!!

Rash (e.g., erythematous, urticarial)1,2,18,32,91,92,120,121,128,132,246,248,249,250 has been reported in about 2% of patients receiving ceftriaxone1,2,18,32,92 and pruritus,1,2,18,32,92,125,248 fever,1,2,18,32,88,92,121,125,128,132,143,250 and chills1,2,18,32,92 have been reported in less than 1% of patients receiving the drug.1,2,18,32

Serious, occasionally fatal, hypersensitivity reactions (anaphylaxis or anaphylactoid) have been reported in patients receiving ceftriaxone.1,2,3,30,32 Bronchospasm1,2,18,32,92,120 and serum sickness1,2,18,32,92 have been reported in less than 0.1% of patients receiving the drug.1,2,18,32

Exanthema, allergic dermatitis, urticaria, and edema have been reported in patients receiving ceftriaxone.1,2,3,18,30,32 There also have been postmarketing reports of generalized exanthematous pustulosis1,2,18,32 and isolated reports of severe cutaneous adverse reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome/toxic epidermal necrolysis).1,2,3,18,30,32

Hepatic Effects !!navigator!!

Increased serum concentrations of AST (SGOT) and ALT (SGPT)1,2,18,32,88,91,93,125,128,249,250,256,265 have been reported in about 3% of patients1,2,18,32,93 and increased serum concentrations of alkaline phosphatase1,2,18,32,125 and bilirubin1,2,18,32 have been reported in less than 1% of patients receiving ceftriaxone.1,2,18,32 Jaundice has been reported in less than 0.1% of patients receiving the drug1,2,18,32 and there have been postmarketing reports of hepatitis.3

Renal Effects !!navigator!!

Increased concentrations of BUN have been reported in about 1% of patients receiving ceftriaxone1,93 and increased concentrations of serum creatinine1,2,18,32,56,93,143,248 and the presence of casts in urine have been reported in less than 1% of patients receiving the drug.1,2,18,32,93 Glycosuria, hematuria, renal precipitates, and nephrolithiasis have been reported in less than 0.1% of patients receiving the drug.1,2,18,32 Oliguria, ureteric obstruction, and post-renal acute renal failure also have been reported.1,2,3,18,30,32

Ceftriaxone-calcium precipitates in the urine have been observed in patients receiving ceftriaxone and may be detected as sonographic abnormalities.1,2,3,18,32 The probability of such precipitates appears to be greatest in pediatric patients.1,2,3,18,32 Patients may be asymptomatic or may develop symptoms of urolithiasis, ureteral obstruction, and post-renal acute renal failure.1,2,3,18,32 The condition appears to be reversible following discontinuance of the drug and conservative management.1,2,3,18,32

Pulmonary and Renal Precipitates !!navigator!!

Fatalities have been reported in some neonates who received ceftriaxone and calcium-containing IV solutions.1,2,18,30,32,32,507,511 A crystalline material was observed in the lungs and kidneys of these neonates at autopsy.1,2,18,30,32 In some cases, the same IV infusion line had been used for both ceftriaxone and the calcium-containing fluid and, in some, a precipitate was observed in the IV infusion line.1,2,18,30,32 At least 1 fatality occurred in a neonate who received ceftriaxone and calcium-containing fluids administered at different times and through different infusion lines; no crystalline material was observed at autopsy in this neonate.1,2,18,30,32,511 (See Interactions with Calcium-containing Products under Cautions: Precautions and Contraindications.) There have been no similar reports in patients other than neonates treated with ceftriaxone and calcium-containing IV solutions.1,18,30,32

To date, there have been no reports of an interaction between ceftriaxone and oral calcium-containing preparations or between IM ceftriaxone and calcium-containing preparations (IV or oral).1,2,18,32,529

Local Effects !!navigator!!

Local reactions, including pain, induration, ecchymosis, and tenderness at the injection site have been reported in patients receiving IM ceftriaxone.1,2,57,81,104,117 The overall incidence of pain, induration, and tenderness following IM injection of the drug is 1-2%.1,2,92,104 The incidence of warmth, tightness, or induration reported following IM injection of ceftriaxone doses of 250 or 350 mg/mL was 5 or 17%, respectively.1,2 Local reactions occur less frequently and are less intense when IM injections of ceftriaxone are reconstituted with 1% lidocaine hydrochloride (without epinephrine) rather than sterile water for injection.57,379 (See Other Precautions and Contraindications under Cautions: Precautions and Contraindications.)

Results of a cross-over study involving IM injection into the buttock of 1-g doses of ceftriaxone diluted in 2 mL of sterile water for injection, 1% lidocaine, or 1% lidocaine buffered with sodium carbonate indicate that the pharmacokinetics of ceftriaxone are not affected by the diluent; however, use of a lidocaine diluent was associated with a 50-78% reduction in injection pain scores compared with use of sterile water for injection.379 Buffered lidocaine did not appear to offer any advantages over unbuffered lidocaine.379

Phlebitis has been reported in less than 1% of patients receiving IV ceftriaxone.1,2,18,32,92,104,121,129

Other Adverse Effects !!navigator!!

Other adverse effects that have been reported in less than 1% of patients receiving ceftriaxone include diaphoresis and flushing,1,2,18,32,92 headache,1,2,18,32,92 dizziness,1,2,18,32,92 oral candidiasis,104,122 and candidal vaginitis.1,88,92 Palpitation and epistaxis have been reported in less than 0.1% of patients receiving the drug.1,2,18,32

In at least one patient, inadvertent IV injection over 5 minutes of a 2-g dose of ceftriaxone resulted in a reaction that consisted of restlessness, shivering, diaphoresis with dilated pupils, and palpitations; this reaction did not occur when the drug was administered by IV infusion over 30 minutes as recommended by the manufacturer.420

Precautions and Contraindications !!navigator!!

Ceftriaxone is contraindicated in patients with known hypersensitivity to ceftriaxone, any other cephalosporin, or any ingredient in the formulation.1,2,18,30,32 Patients with previous hypersensitivity reactions to penicillin and other β-lactam anti-infectives may be at greater risk of hypersensitivity to ceftriaxone.1,2,18,32 Some manufacturers state that ceftriaxone is contraindicated in patients with a history of anaphylaxis to ceftriaxone, other cephalosporins, penicillins, or other β-lactam anti-infectives.3 (See Sensitivity Reactions under Cautions: Precautions and Contraindications.)

Ceftriaxone is contraindicated in certain neonates (e.g., premature or hyperbilirubinemic neonates, those requiring calcium-containing IV solutions).1,2,18,30,32 (See Cautions: Pediatric Precautions.)

Ceftriaxone shares the toxic potentials of the cephalosporins, and the usual precautions of cephalosporin therapy should be observed.1,2,3,18,30,32

Sensitivity Reactions

Prior to initiation of therapy with ceftriaxone, careful inquiry should be made concerning previous hypersensitivity reactions to ceftriaxone, cephalosporins, penicillins, other β-lactam anti-infectives, or other drugs.1,2,3,18,30,32 There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins and cephamycins.3,170,184,325,432,433

As with all β-lactam anti-infectives, serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with ceftriaxone.1,2,18,30,32

Although it has not been proven that allergic reactions to antibiotics are more frequent in atopic individuals,182,183,184 some manufacturers state that ceftriaxone should be used with caution in patients with a history of allergy, particularly to drugs.1,2,18,30,32

The manufacturer of the commercially available frozen premixed ceftriaxone injection in dextrose states that dextrose-containing solutions may be contraindicated in patients with known allergy to corn or corn products.30 Hypersensitivity reactions, including anaphylaxis, have been reported with administration of dextrose products.3 These reactions have been reported in patients receiving high concentrations of dextrose (i.e., 50% dextrose) and also have been reported when corn-derived dextrose solutions were administered to patients with or without a history of hypersensitivity to corn products.3

Patients should be advised that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment.3

If a severe hypersensitivity reaction occurs during ceftriaxone therapy, the drug should be discontinued immediately and the patient treated with appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.1,2,3,18,30,32

Interaction with Calcium-containing Products

Because of the risk of precipitation of ceftriaxone-calcium and because fatalities associated with ceftriaxone-calcium precipitates in lungs and kidneys have been reported in neonates (see Cautions: Pulmonary and Renal Precipitates), ceftriaxone is contraindicated in neonates (28 days of age or younger) who are receiving (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition.1,2,18,30,32,529

Intravascular or pulmonary ceftriaxone-calcium precipitates have not been reported to date in patients other than neonates treated with ceftriaxone and calcium-containing IV solutions.1,2,3,18,30,32 There is some evidence that neonates have an increased risk for precipitation of ceftriaxone-calcium.1,2,3 In vitro studies evaluating the combination of ceftriaxone and calcium in adult plasma and neonatal plasma from umbilical cord blood indicate that recovery of ceftriaxone from plasma was reduced in adult plasma when calcium concentrations were 24 mg/dL or greater and was reduced in neonatal plasma when calcium concentrations were 16 mg/dL or greater.1,2,3 This may reflect ceftriaxone-calcium precipitation.1,2,18,30,32

Ceftriaxone must not be admixed with calcium-containing IV solutions and must not be administered simultaneously with calcium-containing IV solutions, including continuous infusions of calcium-containing solutions such as parenteral nutrition, even via different infusion lines or sites in any patient (irrespective of age).1,2,3,18,30,32,507,511,529 In adults or pediatric patients older than 28 days of age, ceftriaxone and calcium-containing solutions may be administered sequentially if the IV infusion lines are thoroughly flushed between infusions with a compatible fluid.1,2,3,30,32,529 (See Dosage and Administration: Reconstitution and Administration.)

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftriaxone and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1,2,3,18,30,32 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1,2,3,18,30,32 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1,2,3,18,30,32

Patients should be advised that antibacterials (including ceftriaxone) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1,2,3,18,30,32 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftriaxone or other antibacterials in the future.1,2,3,18,30,32

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Use of ceftriaxone may result in overgrowth of nonsusceptible organisms,1,2,18,32,119,121,125,132,150,246,249,250,265 especially Candida , enterococci, Bacteroides fragilis , or Pseudomonas aeruginosa .119,121,125,132,150,246,249,250,265 Resistant strains of Ps. aeruginosa 120,121,127,131,132,150 and Enterobacter 120,121,132,150 have developed during therapy with ceftriaxone. (See Resistance.) Careful observation of the patient during ceftriaxone therapy is essential.1,2,18,32 If superinfection or suprainfection occurs, appropriate therapy should be instituted.1,2,18,32

Because CDAD has been reported with the use of ceftriaxone or other cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after ceftriaxone therapy.1,2,3,18,30,32,190,303,304,305,328 (See Clostridium difficile-associated Diarrhea and Colitis under Cautions: GI Effects.) Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, they should contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1,2,3,18,30,32

Some manufacturers state that ceftriaxone should be used with caution in patients with a history of GI disease, particularly colitis.1,2,18,30,32

Other Precautions and Contraindications

Because potentially fatal immune-mediated hemolytic anemia has been reported with cephalosporins, including ceftriaxone, the diagnosis of cephalosporin-associated anemia should be considered if anemia occurs in a patient receiving ceftriaxone.1,2,3,18,30,32 The drug should be discontinued until the etiology of the anemia is determined.1,2,18,30,32

Ceftriaxone can precipitate in the gallbladder.1,2,3,18,30,32,209,247,248,308,309 (See Cautions: GI Effects.) Some clinicians recommend that ceftriaxone be used with caution in patients with preexisting disease of the gallbladder,248,256,309 biliary tract,248 liver,248,256 or pancreas,248 and, if the drug is used in such patients, serial abdominal ultrasonography should be performed during therapy.248,309 Ceftriaxone should be discontinued and conservative management considered in any patient who develops signs and symptoms suggestive of gallbladder disease, including sonographic abnormalities.1,2,3,18,30,32,248,256,308,309

Ceftriaxone can precipitate in the urinary tract.1,2,3,18,32 (See Cautions: Renal Effects.) Patients receiving the drug should be adequately hydrated.1,2,3,18,32 Ceftriaxone should be discontinued if there are signs and symptoms suggestive of urolithiasis, oliguria, or renal failure and/or if sonographic abnormalities are detected.1,2,3,18,32

Because prolonged PT has been reported in patients receiving ceftriaxone, the manufacturers state that PT should be monitored when the drug is used in patients with impaired vitamin K synthesis or low vitamin K stores (e.g., patients with chronic hepatic disease, malnutrition).1,2,18,30,32 The manufacturers state that administration of vitamin K (10 mg weekly) may be necessary if the PT is prolonged before or during ceftriaxone therapy.1,2,18,30,32 Concomitant use of ceftriaxone and vitamin K antagonists may increase the risk of bleeding.1,2,18,30,32 (See Drug Interactions: Anticoagulants.)

Seizures have been reported with some cephalosporins, including ceftriaxone.1,2,3,18,30,32 Ceftriaxone should be discontinued if seizures occur and anticonvulsant therapy should be administered if clinically indicated.1,2,3,18,30,32 Patients should be advised that adverse neurologic events can occur and to immediately contact a clinician if any neurologic signs and symptoms, including encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, coma), myoclonus, or seizures, occur since immediate treatment, dosage adjustment, or discontinuance of ceftriaxone therapy is required.3

Like other dextrose-containing solutions, the commercially available Duplex® drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection should be used with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.3

Although IM injections of ceftriaxone may be prepared using diluents containing 1% lidocaine hydrochloride (see IM Injection under Dosage and Administration: Reconstitution and Administration), all contraindications to lidocaine should be considered before administering such injections.1,2 IV administration of ceftriaxone solutions containing lidocaine is contraindicated.1,2,18,32

Dosage adjustments are not usually necessary when ceftriaxone is used in patients with renal impairment or hepatic impairment alone.1,2,18,32,73,74,77,84,85,104,105,107,170 Some clinicians recommend that serum concentrations of the drug be monitored when ceftriaxone is used in patients with severe renal impairment (e.g., dialysis patients) or in patients with hepatic impairment and clinically important renal impairment.73,74,77,170 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

Pediatric Precautions !!navigator!!

Ceftriaxone is contraindicated in premature neonates up to postmenstrual age 41 weeks (i.e., time elapsed since first day of the mother's last menstrual period to birth plus time elapsed after birth).1,2,18,32

Ceftriaxone is contraindicated in hyperbilirubinemic neonates, particularly those who are premature.1,2,18,30,32,507 Ceftriaxone, at therapeutic concentrations, has been shown to displace bilirubin from albumin binding sites in vitro.1,2,18,30,32,237,238 Because ceftriaxone can displace bilirubin from serum albumin,1,2,18,30,32,237,238 there is a risk that bilirubin encephalopathy could develop if the drug is used in hyperbilirubinemic neonates.1,2,18,30,32,507 Addition of ceftriaxone to blood samples obtained from hyperbilirubinemic neonates resulted in increased free and erythrocyte-bound bilirubin concentrations and decreased unconjugated (albumin-bound) bilirubin concentrations.237

Ceftriaxone is contraindicated in neonates (28 days of age or younger) if they are receiving (or expected to require) treatment with calcium-containing IV solutions, including continuous infusions of calcium-containing solutions such as parenteral nutrition, because of the risk of precipitation of a ceftriaxone-calcium salt.1,2,18,30,32,529 Fatalities associated with ceftriaxone-calcium precipitates in lungs and kidneys have been reported in neonates who received ceftriaxone and calcium-containing IV solutions.1,2,18,30,32,507 (See Cautions: Pulmonary and Renal Precipitates and see Interaction with Calcium-containing Products under Cautions: Precautions and Contraindications.)

To reduce the risk of bilirubin encephalopathy, IV infusions of ceftriaxone should be given over 60 minutes in neonates.1,2,18,32 (See Dosage and Administration: Reconstitution and Administration.)

Ceftriaxone that has been reconstituted for IM use with bacteriostatic water for injection containing benzyl alcohol should not be used in neonates.176,177 Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.176,177 Toxicity appears to have resulted from administration of large amounts (i.e., about 100-400 mg/kg daily) of benzyl alcohol in these neonates.176,177

To avoid unintentional overdosage, the commercially available Duplex® drug delivery system containing 1 or 2 g of ceftriaxone and 50 mL of dextrose injection in separate chambers should not be used in pediatric patients who require less than the entire 1- or 2-g dose in the container.3

Geriatric Precautions !!navigator!!

In clinical studies, safety and efficacy of ceftriaxone in geriatric adults 60 years of age or older have been similar to those observed in younger adults.1,2,3,18,30,32 Although other clinical experience has revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.1,2,3,18,30,32

The pharmacokinetics of ceftriaxone are only minimally altered in geriatric patients compared with healthy younger adults.1,2,3,18,30,32 Dosage adjustments based solely on age are not necessary in geriatric patients receiving ceftriaxone dosages up to 2 g daily, provided they do not have severe renal and hepatic impairment.1,2,3,18,30,32

Ceftriaxone is substantially eliminated by the kidneys, and the risk of adverse effects may be greater in those with impaired renal function.3 Because geriatric patients are more likely to have reduced renal function, dosage should be selected with caution and monitoring of renal function should be considered.3

Mutagenicity and Carcinogenicity !!navigator!!

In vitro studies using microbial (i.e., Ames test) or mammalian cell (i.e., human lymphoblasts) systems have not shown ceftriaxone to be mutagenic.1,2,18,32 Specific studies to determine the carcinogenic potential of ceftriaxone have not been performed to date, and animal toxicity studies have been performed to a maximum duration of only 6 months.1,2,18,32

Pregnancy, Fertility, and Lactation !!navigator!!

Pregnancy

Reproduction studies in mice, rats, and primates have not revealed evidence of embryotoxicity, fetotoxicity, or teratogenicity.1,2,3,18,30,32 There are no adequate or controlled studies using ceftriaxone in pregnant women, and the drug should be used during pregnancy only when clearly needed.1,2,3,18,30,32

Fertility

Studies in rats using IV ceftriaxone have not revealed evidence of impaired fertility.1,2,3,18,30,32

Lactation

Because ceftriaxone is distributed into milk, the drug should be used with caution in nursing women.1,2,3,18,30,32

Drug Interactions ⬆ ⬇

[Section Outline]

Alcohol !!navigator!!

A disulfiram-like reaction reportedly occurred in one patient who ingested alcohol while receiving ceftriaxone.132 However, this effect generally has been reported only with β-lactam antibiotics that contain an N -methylthiotetrazole (NMTT) side chain (e.g., cefamandole, cefoperazone, cefotetan).105,106

Aminoglycosides !!navigator!!

In vitro studies indicate that the antibacterial activity of ceftriaxone and aminoglycosides (amikacin, gentamicin, tobramycin) may be additive or synergistic against some strains of Enterobacteriaceae and some strains of Pseudomonas aeruginosa .34,36,101,102,103,104,158 Although the clinical importance has not been determined to date, antagonism has also occurred rarely in vitro when ceftriaxone was used in combination with an aminoglycoside.102 Organisms with high-level resistance to both the aminoglycoside and the β-lactam antibiotic alone are unlikely to be synergistically inhibited by concomitant use of the drugs.103

Anticoagulants !!navigator!!

Concomitant use of ceftriaxone and vitamin K antagonists may increase the risk of bleeding.1,2,18,30,32 Increased international normalized ratio (INR) has been reported in patients receiving warfarin and ceftriaxone concomitantly.688,689 In one patient who had been receiving long-term warfarin therapy with stable INR, administration of a single 1-g IM dose of ceftriaxone for the treatment of a urinary tract infection resulted in a substantially increased INR that was managed by withholding a warfarin dose and administering vitamin K.688 If ceftriaxone is used in patients receiving a vitamin K antagonist (e.g., warfarin), coagulation parameters should be monitored frequently and dosage of the anticoagulant adjusted as needed, both during and after ceftriaxone treatment.1,2,18,30,32

Chloramphenicol !!navigator!!

Antagonism has been reported in vitro when ceftriaxone was used in combination with chloramphenicol.1,2,3,18,30,32

Probenecid !!navigator!!

Concomitant administration of oral probenecid (500 mg daily) does not appear to affect the pharmacokinetics of ceftriaxone,1,2,3,18,30,32,84,104,170,179 presumably because ceftriaxone is excreted principally by glomerular filtration and nonrenal mechanisms.84,104,170,179 However, higher dosages of oral probenecid (1 or 2 g daily) administered concomitantly reportedly may partially block biliary secretion of ceftriaxone as well as displace the drug from plasma proteins.179 As a result, serum clearance of ceftriaxone may be increased by about 30% and elimination half-life of ceftriaxone may be decreased by about 20%.179

Quinolones !!navigator!!

Although the clinical importance is unclear, results of an in vitro study indicate that the combination of ceftriaxone and trovafloxacin (not commercially available in the US) is synergistic against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae , including some strains that also were resistant to ceftriaxone alone.485 There was no evidence of antagonism with the combination of ceftriaxone and trovafloxacin.485

Other Information ⬆ ⬇

[Section Outline]

Laboratory Test Interferences

Tests for Glucose !!navigator!!

False-positive results for urinary glucose may occur in patients receiving ceftriaxone if nonenzymatic glucose test methods are used.1,2,18,32 Like most cephalosporins, ceftriaxone interferes with urinary glucose determinations using cupric sulfate (e.g., Benedict's solution, Clinitest®); however, glucose oxidase methods (e.g., Clinistix®, Tes-Tape®) are unaffected by the drug.100 Enzymatic methods should be used to test for urinary glucose in patients receiving ceftriaxone.1,2,18,32

The presence of ceftriaxone may result in falsely low estimated blood glucose concentrations measured using some blood glucose monitoring systems.1,2,18,32 The manufacturer's instructions for the glucose monitoring system should be consulted and alternative testing methods should be used if necessary.1,2,18,32

Tests for Creatinine !!navigator!!

In one in vitro study, high concentrations of ceftriaxone (50 mcg/mL or greater) caused falsely elevated serum creatinine values when a manual method was used;98 however, other studies indicate that the drug does not interfere with automated methods for determining serum or urinary creatinine concentrations.97,98

Acute Toxicity

Limited information is available on the acute toxicity of ceftriaxone; there is no specific antidote.1,2,18,32 If acute overdosage of ceftriaxone occurs, supportive and symptomatic treatment should be initiated.1,2,18,32 Ceftriaxone is not removed by hemodialysis or peritoneal dialysis,1,2,18,32,73,75 and these procedures would be ineffective in reducing ceftriaxone concentrations following overdosage.1,2,18,32

Mechanism of Action

Ceftriaxone usually is bactericidal in action.1,2,3,4,18,22,30,32,41,104 Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall.1,2,3,18,30,32,104 For information on the mechanism of action of cephalosporins, see Mechanism of Action in the Cephalosporins General Statement 8:12.06.

Spectrum

Based on its spectrum of activity, ceftriaxone is classified as a third generation cephalosporin.104,105,106,108,162,165,170 For information on the classification of cephalosporins and closely related β-lactam antibiotics based on spectra of activity, see Spectrum in the Cephalosporins General Statement 8:12.06.

Like other currently available parenteral third generation cephalosporins (e.g., cefotaxime, ceftazidime), ceftriaxone generally is less active in vitro against susceptible staphylococci than first generation cephalosporins4,7,23,36,37,104,105,106,170 but has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.4,23,37,104,105,106,170 The spectrum of activity of ceftriaxone closely resembles that of cefotaxime and ceftazidime.4,7,23,36,37,39,104,105,106,128,170 In vitro on a weight basis, the activity of ceftriaxone against most susceptible organisms, including most Enterobacteriaceae, is approximately equal to that of cefotaxime.4,7,23,36,37,39,46,105,106

In Vitro Susceptibility Testing !!navigator!!

Results of in vitro susceptibility tests with ceftriaxone for some bacteria (e.g., Enterobacter cloacae , Klebsiella pneumoniae , Proteus , Pseudomonas , Serratia , staphylococci) may be affected by the size of the inoculum.7,29,36,37,41,46,104 Although results of ceftriaxone susceptibility tests do not appear to be affected by culture media,36,101,104 results may be affected by pH101,104 or the presence of serum.36,46,203 MICs of ceftriaxone for Staphylococcus aureus , Pseudomonas aeruginosa , or Enterobacteriaceae may be 4-8 times higher when tested in the presence of serum.203

Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to ceftriaxone, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.665

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when ceftriaxone susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), see Spectrum: In Vitro Susceptibility Testing, in the Cephalosporins General Statement 8:12.06.

Gram-positive Aerobic Bacteria !!navigator!!

Ceftriaxone is active in vitro against most gram-positive aerobic cocci including penicillinase-producing and nonpenicillinase-producing strains of Staphylococcus aureus 1,7,14,22,23,36,37,45,104,106,108,121,123 and S. epidermidis ;1,22,23,36,37,45,104,108,121 Streptococcus pneumoniae ;1,4,7,20,22,25,36,37,39,45,106 S. pyogenes (group A β-hemolytic streptococci; GAS);1,4,7,22,23,36,37,45,46,107 S. agalactiae (group B streptococci; GBS);1,7,9,14,22,23,43,45,104,106,128 and viridans streptococci (including the S. milleri group [ S. anginosus , S. constellatus , S. intermedius ]).22,36,45,104,483 Staphylococci resistant to penicillinase-resistant penicillins also generally are resistant to ceftriaxone.1,7,45,104 Group D streptococci1 and enterococci, including E. faecalis (formerly S. faecalis ), generally are resistant to ceftriaxone.1,6,7,14,16,22,23,36,37,39,45,46,104,106,120

The MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of ceftriaxone for penicillinase-producing and nonpenicillinase-producing S. aureus is 3-8 mcg/mL.4,7,14,22,23,36,37,45,104,106,108 The MIC90 of the drug reported for S. epidermidis is 16-50 mcg/mL22,23,36,37,104 and the MIC50 of the drug reported for this organism is 3.1-7.3 mcg/mL.6,36,37,45,108

The MIC90 of ceftriaxone for S. pyogenes 4,7,14,22,23,36,37,45,46,106 is 0.15-0.25 mcg/mL, and the MIC90 of the drug reported for S. agalactiae is 0.06-0.78 mcg/mL.7,9,14,22,23,36,43,45,104,106,128 The MIC90 reported for viridans streptococci is 0.5-4 mcg/mL.22,36,45,104,483 In one study, the MIC50 and MIC90 of ceftriaxone for the S. milleri group of viridans streptococci were 0.25 and 0.5 mcg/mL, respectively.483

Although the MIC90 reported for S. pneumoniae generally is 0.15-0.25 mcg/mL,4,7,20,22,23,36,37,39,45,106 some strains have reduced susceptibility and require ceftriaxone concentrations of 0.5-2 mcg/mL or greater for in vitro inhibition.242,324,333,334,348,434 Strains of S. pneumoniae with MICs of 2 mcg/mL or greater generally are considered resistant to ceftriaxone;324,512 however, strains with MICs of 0.5-1 mcg/mL that are isolated from patients with meningitis generally also are considered resistant to the drug.234

Other Gram-positive Bacteria

Although a few strains of Listeria monocytogenes may be inhibited in vitro by ceftriaxone concentrations of 0.8-32 mcg/mL,9,36,104 most strains of the organism are resistant to the drug.9,45,64,104,106,130

Ceftriaxone is active in vitro against some strains of Nocardia ,526,527,698 including some strains of N. asteroides 527,698 and N. brasiliensis .526 However, resistance to ceftriaxone also has been reported in environmental isolates of N. asteroides 527 and clinical isolates of N. farcinica .701

Gram-negative Aerobic Bacteria !!navigator!!

Neisseria

Ceftriaxone is active in vitro against Neisseria meningitidis ,1,25,36,37,78,106,139 and most strains of this organism are inhibited by ceftriaxone concentrations of 0.001-0.025 mcg/mL.25,36,37,78,106

Ceftriaxone is active in vitro against penicillinase-producing (PPNG) and nonpenicillinase-producing Neisseria gonorrhoeae and those with chromosomally mediated resistance (e.g., to penicillin) (CMRNG) or plasmid-mediated tetracycline resistance (TRNG).1,7,20,23,24,26,27,28,35,36,37,42,46,78,104,106,108,114,118,219,221,225,230,232,233,337 The MIC90 of ceftriaxone reported for N. gonorrhoeae usually is 0.001-0.05 mcg/mL.26,27,28,42,231 However, N. gonorrhoeae with reduced susceptibility to ceftriaxone (MICs 0.125 mcg/mL or greater), including some ceftriaxone-resistant strains, have been reported with increasing frequency during the last decade;720,721,722,725,726,727 some treatment failures have been reported.720,725 (See Resistance.)

Haemophilus

Ceftriaxone is active in vitro against most β-lactamase-producing and non-β-lactamase-producing strains of Haemophilus influenzae ,1,7,14,20,29,36,37,39,42,46,104,108,122 H. parainfluenzae ,1 and H. ducreyi .104,204,210,211,229 The MIC90 of the drug reported for H. influenzae is 0.003-0.03 mcg/mL.7,14,20,29,36,37,42,46,104,108,122 H. ducreyi generally is inhibited in vitro by ceftriaxone concentrations of 0.002-0.06 mcg/mL.104,204,210,211,229

Enterobacteriaceae

Generally, ceftriaxone is active in vitro against the following Enterobacteriaceae: Citrobacter diversus ,1,6,22,36,106 C. freundii ,1,6,7,22,23,36,39,106 Enterobacter cloacae ,1,6,7,106,128 E. aerogenes ,1,7,22,36,106,128 Escherichia coli ,1,4,6,20,22,23,36,37,39,46,101,106,128 Klebsiella pneumoniae ,1,6,20,22,36,39,101 Morganella morganii (formerly Proteus morganii ),1,6,7,20,22,106 Proteus mirabilis ,1,4,6,7,14,20,22,23,36,37,39,106,128 P. vulgaris ,1,7,22 Providencia rettgeri (formerly Proteus rettgeri ),1,7,23,106 P. stuartii ,7,14,20,22,23,39 Serratia marcescens ,1,4,6,7,14,22,23,37,39,128 Salmonella ,1,4,17,36,37,40,106 Shigella ,1,4,14,36,37,106 and Yersinia enterocolitica .23,33,181

The MIC90 of ceftriaxone for most of these Enterobacteriaceae, including Citrobacter ,4,6,7,22,23,36,39,104,106 E. coli ,4,6,7,14,20,22,23,36,37,39,46,106,128 Klebsiella ,4,7,14,22,23,36,37,39,46,47,101,106,128 M. morganii ,6,7,20,22,106 P. vulgaris ,7,22,104 Providencia ,6,7,14,20,22,23,36,37,39,128 and Yersinia enterocolitica ,23,33,181 is 0.05-4 mcg/mL. The MIC90 of the drug for P. mirabilis is 0.006-0.1 mcg/mL.4,6,7,14,20,22,23,36,37,39,106,128 Although the MIC90 of ceftriaxone reported for E. aerogenes generally is 0.12-8 mcg/mL,7,22,36,104,106,128 the MIC90 of the drug reported for E. cloacae is 0.5-25 mcg/mL.6,7,36,104,106,128 The MIC90 of ceftriaxone for S. marcescens is 0.25-32 mcg/mL.4,6,7,14,22,23,37,39,101,106,128

The MIC90 of ceftriaxone reported for Salmonella enteritidis ,17 S. paratyphi ,37 S. sendai ,37 S. typhi ,14,17,40 and S. typhimurium 37 is 0.04-0.1 mcg/mL. Strains of Salmonella resistant to ceftriaxone have been reported rarely.405 Multidrug-resistant Salmonella serotype Newport has been reported with increasing frequency in the US.352 These strains usually are resistant to ampicillin, amoxicillin clavulanate, cefoxitin, cephalothin, chloramphenicol, streptomycin, sulfamethoxazole, or tetracycline and have either decreased susceptibility or resistance to ceftriaxone.352

The MIC90 of ceftriaxone reported for Shigella , including Sh. sonnei , is 0.02-0.5 mcg/mL.4,14,36,37,106

Pseudomonas

Although ceftriaxone is active in vitro against some strains of Ps. aeruginosa ,1,4,5,6,7,10,14,20,22,39,104,158 many strains of the organism require ceftriaxone concentrations of 64 mcg/mL or greater for in vitro inhibition and are therefore considered resistant to the drug.11,23,36,37,101,102,466 Ceftriaxone generally is less active in vitro against susceptible Ps. aeruginosa than ceftazidime or extended-spectrum penicillins (e.g., piperacillin).10,101,106 In some in vitro studies, the MIC50 of ceftriaxone for Ps. aeruginosa was 4-16 mcg/mL and the MIC90 of the drug was 16-32 mcg/mL.4,5,6,7,10,14,20,22,39,158 However, in other studies, the MIC50 was 16-64 mcg/mL and the MIC90 was 64 mcg/mL or greater.11,23,36,37,101,102,466

Ceftriaxone has some activity against Pseudomonas other than Ps. aeruginosa .11,15,22,158,466 The MIC90 of ceftriaxone reported for Ps. acidovorans 11 and Ps. stutzeri 11 is 2-16 mcg/mL, but Ps. fluorescens and Ps. putida generally are resistant to the drug.6,11,22,466

Other Gram-Negative Aerobic Bacteria

Ceftriaxone is active in vitro against Moraxella 11 and Eikenella corrodens ,161 and the MIC90 of the drug reported for these organisms is 1-2 mcg/mL.11,161

While ceftriaxone has some activity in vitro against Acinetobacter 10,11,20,22,23,158,466 and the MIC90 of ceftriaxone reported for A. calcoaceticus and A. lwoffi is 8-32 mcg/mL,11,20,22,23,158 the MIC90 reported for A. baumannii is 64 mcg/mL and this organism is considered resistant to the drug.466

Alcaligenes faecalis may be inhibited in vitro by ceftriaxone concentrations of 0.5 mcg/mL or less; however, A. denitrificans and A. xylosoxidans generally are resistant to the drug.466

Bartonella henselae and B. quintana may be inhibited in vitro by ceftriaxone concentrations of 0.06-0.25 mcg/mL.354 Some strains of B. bacilliformis are inhibited in vitro by ceftriaxone concentrations of 0.003-0.006 mcg/mL.354,482

In one study, all strains of Burkholderia cepacia (formerly Pseudomonas cepacia ) tested were resistant to ceftriaxone.466

Ceftriaxone is active in vitro against Capnocytophaga ,461,462 including C. canimorsus (formerly CDC group DF-2).462 The MIC90 of ceftriaxone reported for Capnocytophaga is 4 mcg/mL.461

Stenotrophomonas maltophilia (formerly Ps. maltophilia or Xanthomonas maltophilia ) generally is resistant to ceftriaxone.6,11,22,466

Some strains of Weeksella virosa are inhibited in vitro by ceftriaxone concentrations of 0.5 mcg/mL or lower.466

Anaerobic Bacteria !!navigator!!

Ceftriaxone is active in vitro against some anaerobic bacteria including Actinomyces ,8 Fusobacterium ,7,8,16,22 Lactobacillus ,7,8 Peptococcus ,7,8,16,19,22 Peptostreptococcus ,7,8,16,19,22 Propionibacterium ,7 and Veillonella .7,8,22 The MIC90 of ceftriaxone reported for most of these anaerobic bacteria is 0.5-16 mcg/mL.7,8,16,19,22,104

Some strains of Clostridium , including C. perfringens , are inhibited in vitro by ceftriaxone concentrations of 0.5-16 mcg/mL;16,19,22,23,36 however, C. difficile generally is resistant to the drug.1,6,8

Most strains of Bacteroides fragilis are resistant to ceftriaxone.6,7,8,14,16,19,22,36 Although the MIC50 of ceftriaxone reported for B. fragilis , B. distasonis , B. ovatus , B. thetaiotaomicron , and B. vulgatus is 2-64 mcg/mL,6,7,8,14,16,19,22,23,36,37,104 the MIC90 is 32 mcg/mL or greater.6,7,8,14,16,19,22,23,36,104

The MIC90 of ceftriaxone reported for Prevotella melaninogenica (formerly Bacteroides melaninogenicus ) is 4-16 mcg/mL.7,8,22

Spirochetes !!navigator!!

Studies in rabbits with experimentally induced syphilis indicate that ceftriaxone has some activity against Treponema pallidum .173

Borrelia burgdorferi , the causative organism of Lyme disease, reportedly may be inhibited in vitro by ceftriaxone concentrations of 0.1-1 mcg/mL;207,283,284,285,340,341 minimum bactericidal concentrations (MBCs) of ceftriaxone for B. burgdorferi generally have ranged from 0.02-0.16 mcg/mL.285,288,289,341

Ceftriaxone is active in vitro against Leptospira .696 In one study, all strains of L. interrogans and L. weilii tested were inhibited in vitro by ceftriaxone concentrations of 0.06 mcg/mL or less.696

Chlamydia !!navigator!!

Studies using a limited number of isolates indicate that some strains of Chlamydia trachomatis are inhibited in vitro by ceftriaxone concentrations of 8-32 mcg/mL; however, the clinical importance of this in vitro activity is unclear.213,214 Ceftriaxone generally is considered to be inactive against C. trachomatis .1

Resistance

For information on possible mechanisms of bacterial resistance to cephalosporins, see Resistance in the Cephalosporins General Statement 8:12.06.

Ceftriaxone generally is stable against hydrolysis by β-lactamases classified as Richmond-Sykes types II, III (TEM types), and V;36,79,104 some PSE types;36,79,104 and most β-lactamases produced by Neisseria gonorrhoeae , Haemophilus influenzae , and staphylococci.36 Ceftriaxone may be inactivated by Richmond type IV β-lactamases,104 and in vitro studies indicate that some β-lactamases produced by Bacteroides , Citrobacter , Enterobacter , Morganella , Proteus , and Pseudomonas can inactivate the drug.36,46,79,104,158 Ceftriaxone generally is as stable as cefotaxime against inactivation by β-lactamases but less stable than cefoxitin.7,36,104

Resistant strains of some organisms, including Enterobacter and Ps. aeruginosa , have developed during therapy with ceftriaxone.12,31,104,120,121,124,127,131,132,150 Although further study is needed, it has been suggested that resistance may develop in many of these organisms because they possess inducible β-lactamases.12,31 These inducible enzymes generally are chromosomally mediated cephalosporinases classified as Richmond-Sykes type I.12 In vitro studies indicate that following exposure to certain β-lactam antibiotics (e.g., cefoxitin), inducible β-lactamases are derepressed.12,31 Inducible β-lactamases appear to inactivate β-lactam antibiotics by binding to the drugs, which prevents them from binding to penicillin-binding proteins of the organism.12,31 Most β-lactam antibiotics, including second and third generation cephalosporins and extended-spectrum penicillins, are inactivated by inducible β-lactamases.12,31

Strains of S. pneumoniae considered resistant to ceftriaxone have been reported with increasing frequency.242,324,348,434 These strains generally have intermediate- or high-level resistance to penicillin G as well as decreased susceptibility to third generation cephalosporins.242,324,333,348 Resistance to ceftriaxone in S. pneumoniae appears to be related to alterations in the target enzymes, penicillin-binding proteins (PBPs), of the organism.332,333,348

N. gonorrhoeae with reduced susceptibility to ceftriaxone and/or cefixime or other cephalosporins have been reported with increasing frequency in the US and elsewhere (e.g., Asia, Europe, Canada).344,716,717,718,719,720,721,722,723,724,725,726,727 Strains with reduced susceptibility to ceftriaxone generally have ceftriaxone MICs of 0.125 mcg/mL or greater.720,721,722,725,726,727 There also have been rare reports of N. gonorrhoeae with high-level ceftriaxone resistance (MICs 1-4 mcg/mL) in some countries (Japan, France, Spain),717,721,727 including at least one patient with pharyngeal gonorrhea.717,721 Susceptibility of N. gonorrhoeae in the US is being monitored by CDC Gonococcal Isolate Surveillance Project (GISP).716,722 GISP data from 2000-2010 indicate that the percentage of US N. gonorrhoeae isolates with elevated ceftriaxone MICs (MICs 0.125 mcg/mL or greater) increased from 0.1% to 0.3% and the percentage with elevated cefixime MICs (MICs 0.25 mcg/mL or greater) increased from 0.2% to 1.4%.716 GISP data regarding N. gonorrhoeae isolates from men who have sex with men indicate that the percentage of isolates with elevated ceftriaxone MICs increased from 0% in 2006 to 1% in 2011 and the percentage of isolates with elevated cefixime MICs increased from 0.2% in 2006 to 3.8% in 2011.722

Pharmacokinetics

In all studies described in the Pharmacokinetics section, ceftriaxone was administered as ceftriaxone sodium; dosages and concentrations of the drug are expressed in terms of ceftriaxone.

Ceftriaxone exhibits nonlinear dose-dependent pharmacokinetics.49,50,51,52,54,55,56,74,84,104,170 Serum concentrations, the area under the serum concentration-time curve (AUC), and most pharmacokinetic parameters (except elimination half-life and the fraction excreted unchanged in urine) of total ceftriaxone (both protein-bound and unbound drug) are dose dependent and increase nonlinearly with increases in dosage.49,50,51,54,55,56,74,84,104,170 However, pharmacokinetic parameters of free (unbound) ceftriaxone are not dose dependent and increase linearly with dosage.49,51,54,55,74,84,104,170 Dose-dependent changes in the pharmacokinetic parameters of ceftriaxone apparently occur because the drug exhibits concentration-dependent protein binding.49,51,54,55,84,104,170 (See Pharmacokinetics: Distribution.) Some clinicians suggest that because of this concentration-dependent protein binding, distribution and clearance parameters calculated with data obtained using concentrations of total ceftriaxone may be invalid and misleading.49,50,52,55 Other clinicians suggest that concentration-dependent protein binding and dose-related changes in the pharmacokinetic parameters of ceftriaxone over the usual dosage range of the drug are small and not clinically important.55,56,84,170

Absorption !!navigator!!

Ceftriaxone is not appreciably absorbed from the GI tract and must be given parenterally.170

Following IM administration of a single ceftriaxone dose of 0.5-1 g in healthy adults, the drug appears to be completely absorbed,1,52,57,84 and peak serum concentrations are attained 1.5-4 hours after the dose.1,48,52,57 In one study in healthy adults who received a single 1-g IM dose of ceftriaxone, serum concentrations of the drug averaged 28.9, 43.7, 62.3, 83.2, 40.6, 35.5, and 7.8 mcg/mL at 0.25, 0.5, 1, 2, 6, 12, and 24 hours, respectively, after the dose.48

Following IV infusion over 30 minutes of a single 1-g dose of ceftriaxone in healthy adults, peak serum concentrations of the drug at completion of the infusion average 123.2-150.7 mcg/mL and serum concentrations at 1, 2, 6, 12, and 24 hours after start of the infusion average 109.5-111, 60.8-88.2, 33-52.5, 20.2-28.1, and 4.6-9.3 mcg/mL, respectively.48,55 IV infusion over 30 minutes of a single 2-g dose of ceftriaxone in healthy adults results in peak serum concentrations of the drug at completion of the infusion that range from 223-276 mcg/mL and serum concentrations at 1, 2, 6, 12, and 24 hours after start of the infusion that range from 166-209, 135-173, 75-104, 32-58, and 7-22 mcg/mL, respectively.55

In one study in healthy adults, a ceftriaxone dosage of 2 g daily was given either as 1 g every 12 hours or 2 g every 24 hours; each dose was administered by IV infusion over 30 minutes.56 At steady state, peak serum concentrations of the drug ranged from 132-213 mcg/mL in those who received 1 g every 12 hours and from 216-281 mcg/mL in those who received 2 g every 24 hours; trough serum concentrations ranged from 23-58 and 7-27 mcg/mL, respectively.56 Average steady-state serum concentrations of ceftriaxone were similar for both regimens and were 72 mcg/mL when 1 g was given every 12 hours and 63 mcg/mL when 2 g was given every 24 hours.56

In multiple-dose studies in healthy adults who received a ceftriaxone dosage of 0.5-2 g given every 12 or 24 hours by IM injection or IV infusion over 30 minutes, serum concentrations of the drug at steady state on the fourth day of therapy were 15-36% higher than serum concentrations attained with single doses of the drug.1,56,84,170

In one study in adults with neoplastic disease, IM administration of a single 500-mg dose of ceftriaxone resulted in serum concentrations of the drug averaging 28, 31.9, 32.9, 28.3, and 25.5 mcg/mL at 0.5, 1, 2, 4, and 6 hours, respectively, after the dose.58 IV infusion over 5 minutes of a single ceftriaxone dose of 500 mg or 1 g in these patients resulted in serum concentrations of the drug at 0.5, 1, 2, 4, and 8 hours that averaged 54.4, 44.7, 33.5, 25.4, and 16.8 mcg/mL, respectively, after the 500-mg dose and 79.3, 65.7, 52.2, 28.7, and 22.3 mcg/mL, respectively, after the 1-g dose.58

In one study in neonates and children 1-45 days of age with meningitis who received a single ceftriaxone dose of 50 mg/kg by IV infusion over 15 minutes, serum concentrations of the drug immediately following the infusion and 1, 2, 4, and 6 hours later averaged 136-173, 91-116, 80-112, 70-86, and 66-74 mcg/mL, respectively.63 In another study in neonates 1-4 days of age with meningitis who received a single 50-mg/kg dose of ceftriaxone by IV infusion over 5 minutes, serum concentrations of the drug 1, 12, and 24 hours after the dose ranged from 108-141, 43-76, and 20-52 mcg/mL, respectively.60 Serum concentrations of ceftriaxone in neonates 9-30 days of age with meningitis who received a single 100-mg/kg dose of the drug by IV infusion over 5 minutes ranged from 100-262, 43-140, and 8-33 mcg/mL at 1, 12, and 24 hours, respectively, after the dose.60

In one study in children 7-15 months of age who received a single ceftriaxone dose of 50 mg/kg by IV infusion over 5 minutes, serum concentrations of the drug ranged from 139-197, 66.6-99.2, 31.3-58.9, 2.4-14.8, and 0.85-8.4 mcg/mL at 0.5, 4, 8, 24, and 32 hours, respectively, after the dose.59 When the same dose was administered by IV infusion over 5 minutes to children 2-6 years of age, serum concentrations of the drug at the same time intervals ranged from 180-209, 74.4-108, 32.5-70.2, 5.1-16.1, and 2.4-7.3 mcg/mL, respectively.59 In another study in children 2 months to 16 years of age with CNS infections who received a single ceftriaxone dose of 50 or 75 mg/kg by IV infusion over 15 minutes, peak serum concentrations of the drug occurred immediately following the infusion and ranged from 162-370 mcg/mL after the 50-mg/kg dose and 218-348 mcg/mL after the 75-mg/kg dose; serum concentrations of the drug 12 hours after the dose ranged from 8-56.7 and 13.4-51.2 mcg/mL, respectively.62

Distribution !!navigator!!

The volume of distribution of ceftriaxone is dose dependent and ranges from 5.8-13.5 L in healthy adults.1,53,54,55,56,57,107,170 The volume of distribution of the drug averages 8.5-9.4 L in healthy adults following a single 500-mg dose of the drug and 10-11.4 L following a single 2-g dose.54,55,56,57 The volume of distribution of ceftriaxone is 0.497-0.608 L/kg in neonates 1-45 days of age60,63 and 0.26-0.54 L/kg in children 1.5 months to 16 years of age following a single ceftriaxone dose of 50-100 mg/kg.59,60,61,62,64

Following IM or IV administration, ceftriaxone is widely distributed into body tissues and fluids including the gallbladder,1,84,104 lungs,104,159,355 bone,68,104,489 heart,378 bile,1,69,72,84,104 prostate adenoma tissue,157 uterine tissue,71,104 atrial appendage,68 sputum,104 tears,104 middle ear fluid,1,488 and pleural,104 peritoneal,104 synovial,104 ascitic,104,105 and blister104,170 fluids.

In pediatric patients with otitis media who received a single 50-mg/kg IM dose of ceftriaxone, peak concentrations of ceftriaxone (both protein-bound and unbound drug) in middle ear fluid were attained 24-30 hours after the dose and averaged 35 mcg/mL; middle ear fluid concentrations 48-52 hours after the dose averaged 19 mcg/mL.1,488

In one study in adults with normal hepatobiliary and renal function who received a single 500-mg IV dose of ceftriaxone, peak concentrations of the drug in bile occurred 1-2 hours after the dose and concentrations in bile were generally 2-5 times higher than concurrent serum concentrations.69 In another study in patients who received a single 1-g IV dose of ceftriaxone, concentrations of the drug in specimens obtained 1-3 hours after the dose averaged 62.1 mcg/mL in plasma, 78.2 mcg/g in the gallbladder wall, and 581, 788, and 898 mcg/mL in gallbladder, common duct, and cystic duct biles, respectively.1

In one study in patients undergoing open heart surgery who received a single 1-g IV dose of ceftriaxone approximately 1 hour prior to surgery, concentrations of the drug in the right atrial appendage ranged from 3.6-10.2 mcg/g in samples obtained 1.5-3 hours after the dose.68 In a study in patients undergoing abdominal or vaginal hysterectomy who received a single 2-g IV dose of ceftriaxone, peak concentrations of the drug in gynecologic tissue occurred during the first 2 hours after the dose and concentrations of the drug were higher in the salpinges than in myometrium or endometrium.71 Ceftriaxone concentrations in the salpinges averaged 53.1 and 31.3 mcg/mL at 1-2 and 4-5 hours, respectively, after the dose, and concentrations in myometrium or endometrium averaged 29.8-36.6 and 21.4-24.9 mcg/mL at 1-2 and 4-5 hours, respectively, after the dose.71

Only low concentrations of ceftriaxone are distributed into aqueous humor following IV or IM administration of the drug.70,104 In one study in patients undergoing cataract surgery who received a single 1- or 2-g dose of ceftriaxone by IV infusion over 10 minutes, peak concentrations of the drug in aqueous humor were attained approximately 2 hours after the dose and averaged 0.93 and 2.47 mcg/mL, respectively.70 Aqueous humor concentrations averaged 0.88 mcg/mL 12 hours after the 1-g dose and were 2.1 and 2.5 mcg/mL in two patients 12 hours after the 2-g dose.70

Ceftriaxone generally diffuses into CSF following IM or IV administration of the drug;1,60,61,62,64,65,84,104,105,107,141,170 however, CSF concentrations of the drug are higher in patients with inflamed meninges than in those with uninflamed meninges.65,84,104 Studies in neonates and children with meningitis indicate that peak CSF concentrations of ceftriaxone generally are attained 3-6 hours after an IV dose of the drug,1,60,61,64,84 and CSF concentrations of ceftriaxone may be 1-32% of concurrent serum concentrations.60,61,62,64,65,84,105,107,140,141,142 CSF concentrations of ceftriaxone do not generally correlate with CSF leukocyte cell counts or CSF protein or glucose concentrations.61,65,141 In one study in neonates and children with meningitis who received a single 50- or 100-mg/kg dose of ceftriaxone, CSF concentrations of the drug were 5-31.6 and 1.4-4.5 mcg/mL at 4 and 24 hours, respectively, after the dose.60 In another study in children 2-42 months of age with meningitis who received a single ceftriaxone dose of 50 mg/kg given by IV infusion over 10-15 minutes, CSF concentrations of the drug averaged 1.2-3, 1.4-4.3, and 2.8-7.2 mcg/mL at 1, 4, and 6 hours, respectively, after the dose.61 In one adult with meningitis who received 2 g of the drug once daily, the concentration in CSF was 8.5 mcg/mL in a specimen obtained 5 hours after the third dose of the drug.138

The degree of protein binding of ceftriaxone is concentration dependent and decreases nonlinearly with increasing concentrations of the drug.1,49,50,54,55,56,59,84,104,105,162,170,205 It has been suggested that ceftriaxone may have more than one concentration-dependent protein binding site.205 The drug is 93-96% bound to plasma proteins at a concentration less than 70 mcg/mL,1,84,105,170,205 84-87% bound at a concentration of 300 mcg/mL,1,84,105,170 and 58% or less bound at a concentration of 600 mcg/mL.170 Ceftriaxone binds mainly to albumin.84,104,170 Protein binding of ceftriaxone is lower in neonates and children than in adults because of decreased plasma albumin concentrations in this age group.59,104,178 In one study in children 7 months to 6 years of age with ceftriaxone plasma concentrations of 118-202 mcg/mL, ceftriaxone was 80-87% bound to plasma proteins.59 Ceftriaxone also is less protein bound in patients with renal or hepatic impairment as the result of decreased plasma albumin concentrations or displacement from protein binding sites by bilirubin and other endogenous compounds that may accumulate.74,76

Ceftriaxone crosses the placenta and is distributed into amniotic fluid.66,84,104 In one study in women who received a single 2-g dose of ceftriaxone given by IV injection over 2-5 minutes during labor, peak concentrations of the drug in cord blood, amniotic fluid, and the placenta occurred 4-8 hours after the dose;66 ceftriaxone concentrations in the first voided urine of infants born to these women ranged from 6-92 mcg/mL.66 Ceftriaxone also is distributed into milk in low concentrations.66,84,104 In one study in lactating women who received a single 1-g IM or IV dose of ceftriaxone, peak concentrations of the drug in milk occurred 4-6 hours after the dose and the AUC for milk was 3-4% of the AUC for serum.66

Elimination !!navigator!!

Plasma concentrations of ceftriaxone decline in a biphasic manner.48,55,57,170,172,178 In adults with normal renal and hepatic function, the distribution half-life (t½α) of ceftriaxone is 0.12-0.7 hours55,57,172 and the elimination half-life (t½β) is 5.4-10.9 hours.1,48,51,52,53,54,55,56,57,58,84,104,105,170,172

Ceftriaxone is excreted both by renal and nonrenal mechanisms.1,72,84,104,170 The drug is excreted principally in urine by glomerular filtration and also is excreted in feces via bile.72,84,104,170 Following IM or IV administration of a single dose of ceftriaxone in adults with normal renal and hepatic function, 33-67% of the dose is excreted in urine as unchanged drug and the remainder of the dose is excreted in feces as unchanged drug and microbiologically inactive metabolites.1,84,170 Ceftriaxone is metabolized to a small extent in the intestines after biliary excretion.84

Following IM or IV administration of a single 1-g dose of ceftriaxone in healthy adults, urinary concentrations of the drug average 504-995 mcg/mL in urine collected over the first 2 hours after the dose, 293-418 mcg/mL in urine collected 4-8 hours after the dose, and 132 mcg/mL in urine collected 12-24 hours after the dose.1,55,84

Serum clearance of ceftriaxone is dose dependent and ranges from 9.7-25 mL/minute in healthy adults.48,53,54,55,56,57,84 The serum clearance of the drug averages 10.2-16.7 mL/minute in healthy adults following a single 500-mg IV dose and 19.8-21.6 mL/minute following a single 2-g IV dose.54,55,56,57,104 In children 2 months to 16 years of age who receive a single ceftriaxone dose of 50-100 mg/kg, the serum clearance of ceftriaxone averages 32-40.8 mL/minute per 1.73 m2.61,62 Preliminary studies in patients with cystic fibrosis suggest that serum clearance of ceftriaxone is higher in these patients than in healthy individuals.84

The serum half-life of ceftriaxone is longer in neonates than in older children and adults.104,178 In one study, the serum half-life of ceftriaxone was longer in neonates weighing less than 1.5 kg than in heavier neonates.63,104 Results of another study in neonates 1-8 days of age weighing 1.8-3.9 kg suggested that there was no correlation between weight and serum half-life of the drug at this weight range.181 In one study, the serum half-life of the drug averaged 16.2 hours in neonates 1-4 days of age and 9.2 hours in those 9-30 days of age.60 The serum half-life of ceftriaxone in children is similar to that reported in adults, and the elimination half-life of the drug averages 4-7.7 hours in children 1.5 months to 16 years of age.59,61,62,64,104 In one study in children 2-42 months of age, the t½α of ceftriaxone averaged 0.25 hours and the t½β of the drug averaged 4 hours.61

The elimination half-life of ceftriaxone is only slightly prolonged in patients with moderately impaired renal function and has been reported to range from 10-16 hours in adults with creatinine clearances of 5-73 mL/minute.1,48,77,85,104,170 In patients with creatinine clearances less than 5 mL/minute, the elimination half-life of ceftriaxone has generally been reported to average 12.2-18.2 hours.48,73,74,75,77 However, the elimination half-life of ceftriaxone was 15-57 hours in several uremic patients with creatinine clearances less than 5 mL/minute who had no apparent liver impairment.73,74,77,104,170

Studies in patients with hepatic impairment (e.g., patients with fatty liver, liver fibrosis, compensated liver cirrhosis) indicate that the pharmacokinetics of ceftriaxone are not generally altered in these patients.48,76,85,170 Although the elimination half-life of ceftriaxone was not prolonged in patients with ascites, the volume of distribution and plasma clearance of the drug were increased slightly compared with healthy individuals and averaged 22 L and 28 mL/minute, respectively.104

Ceftriaxone is not removed by hemodialysis1,73,75,77,84,104,105,170 or peritoneal dialysis.75,170

Chemistry and Stability

Chemistry !!navigator!!

Ceftriaxone is a semisynthetic cephalosporin antibiotic.1,2,3,16,18,30,32,104,105,106,165,171 Like cefepime, cefotaxime, and ceftazidime, ceftriaxone is a parenteral aminothiazolyl cephalosporin.105,107,165,170,174 Ceftriaxone contains an aminothiazolyl-acetyl side chain, with a methoxyimino group, at position 7 of the cephalosporin nucleus.105,107,165,170,174 The aminothiazolyl side chain enhances antibacterial activity, particularly against Enterobacteriaceae, and generally results in enhanced stability against β-lactamases; the methoxyimino group contributes to stability against hydrolysis by many β-lactamases.106,107,165,174 Ceftriaxone also has an acidic enol in the triazine moiety at position 3 of the cephalosporin nucleus, which presumably is responsible for the long serum half-life of the drug.165,171

Ceftriaxone is commercially available as the disodium salt;1,2,3,18,30,32,163 however, the drug is referred to as ceftriaxone sodium.163 Potency of ceftriaxone sodium is expressed in terms of ceftriaxone.1,2,3,18,30,32,163 Each mg of ceftriaxone sodium contains not less than 776 mcg of ceftriaxone, calculated on the anhydrous free acid basis.163,275

Ceftriaxone sodium is readily soluble in water,1,2,3,18,30,32,18 having an aqueous solubility of 400 mg/mL at 25°C.171 The drug has a solubility of 1 mg/mL in alcohol at 25°C.18 Ceftriaxone sodium has pKas of 3, 3.2, and 4.1.170,171 Ceftriaxone sodium contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone.1,2,3,18,30,30,32

Commercially available sterile ceftriaxone sodium powder for injection occurs as a white to yellowish or yellowish-orange crystalline powder.1,2,18,32 When reconstituted as directed, solutions of the drug are light yellow to amber in color depending on the diluent used, concentration of the drug, and length of storage.1,2,18,32 The pH of an aqueous solution containing 10 mg of ceftriaxone per mL is approximately 6.7.1,2,18,32

When the commercially available Duplex® drug delivery system that contains 1 or 2 g of ceftriaxone powder and 50 mL of dextrose injection in separate chambers is reconstituted (activated) according to the manufacturer's directions, the resultant solution is iso-osmotic and has an osmolality of approximately 290 mOsm/kg.3

Commercially available frozen premixed ceftriaxone sodium injections in dextrose are sterile, nonpyrogenic, iso-osmotic solutions of the drug provided in a plastic container (Galaxy® containers) fabricated from specially formulated multilayered plastic PL 2040 plastic.30 The 1- and 2-g frozen injections of ceftriaxone contain approximately 1.9 and 1.2 g of dextrose hydrous, respectively, to adjust osmolality and may contain sodium hydroxide and/or hydrochloric acid to adjust pH.30 After thawing, the injections are light yellow to amber in color and have a pH of 6-8.30

Stability !!navigator!!

Commercially available ceftriaxone sodium sterile powder for injection should be stored at 20-25°C and protected from light.1,2,18 It is unnecessary to protect reconstituted solutions of the drug from normal light.1,2,18

Following reconstitution of ceftriaxone powder for injection with sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection, ceftriaxone sodium solutions for IM injection containing approximately 250 or 350 mg of ceftriaxone per mL are stable for 24 hours at room temperature (25°C) or 3 days refrigerated at 4°C and solutions containing approximately 100 mg/mL are stable for 2 days at 25°C or 10 days at 4°C.1,2 Following reconstitution with 1% lidocaine hydrochloride injection (without epinephrine) or bacteriostatic water for injection (containing 0.9% benzyl alcohol), solutions of the drug for IM injection containing 250 or 350 mg/mL are stable for 24 hours at 25°C or 3 days at 4°C and solutions containing 100 mg/mL are stable for 24 hours at 25°C or 10 days at 4°C.1,2

Following reconstitution of ceftriaxone powder for injection as directed by the manufacturer and further dilution with sterile water for injection, 0.9% sodium chloride injection, or 5 or 10% dextrose injection, solutions containing 10-40 mg of ceftriaxone per mL are stable in glass or PVC containers for 2 days at room temperature (25°C) or 10 days when refrigerated at 4°C.1,2,18 If 5% dextrose in 0.45 or 0.9% sodium chloride is used for dilution, solutions of the drug containing 10-40 mg/mL are stable for 2 days at room temperature when stored in glass or PVC containers but are unstable at 4°C.1,2,18 Solutions of the drug containing 10-40 mg/mL are stable for 24 hours at room temperature (25°C) in 10% invert sugar, 5% sodium bicarbonate, 5 or 10% mannitol, FreAmine® III, Normosol®-M in 5% dextrose, or Ionosol® B in 5% dextrose when stored in glass containers.1,2,18 The same concentrations of the drug are stable for 24 hours at room temperature in sodium lactate or Normosol®-M in 5% dextrose when stored in PVC containers.1,2,18

The manufacturers state that following reconstitution with 0.9% sodium chloride injection or 5% dextrose injection, extemporaneously prepared ceftriaxone sodium solutions containing 10-40 mg of ceftriaxone per mL are stable for 26 weeks when frozen at -20°C in PVC or polyolefin containers.1,2,18 Frozen solutions of ceftriaxone sodium should be thawed at room temperature;1,2,18 once thawed, unused portions should be discarded and should not be refrozen.1,2,18

Commercially available 10-g pharmacy bulk packages of ceftriaxone that have been reconstituted to a concentration of 100 mg/mL with a compatible IV solution should be further diluted in a compatible IV infusion solution without delay; any unused portions of the reconstituted solution should be discarded after 4 hours.18

Following reconstitution of ADD-Vantage® vials containing 1 or 2 g of ceftriaxone with 0.9% sodium chloride injection or 5% dextrose injection according to the manufacturer's directions, IV solutions containing 10-40 mg/mL in 0.9% sodium chloride or 5% dextrose in ADD-Vantage® flexible containers are stable for 2 days at room temperature (25°C) or 10 days refrigerated at 4°C.32

The commercially available Duplex® drug delivery system that contains 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose injection should be stored at 20-25°C, but may be exposed to 15-30°C.3 Following reconstitution (activation), these IV solutions must be used within 24 hours if stored at room temperature or within 7 days if stored in a refrigerator and should not be frozen.3

The commercially available frozen premixed ceftriaxone sodium injection in dextrose should be stored at -20°C or lower.30 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.30 Thawed solutions of the commercially available frozen injection are stable for 48 hours at room temperature (25°C) or 21 days under refrigeration (5°C).30 The commercially available frozen injection of the drug is provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy®) .30 Solutions in contact with PL 2040 can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.30

Ceftriaxone is physically incompatible with aminoglycosides, fluconazole, and vancomycin, and the manufacturers state that ceftriaxone should not be admixed with these drugs.1,2,18,30,32 If an aminoglycoside, fluconazole, or vancomycin is to be administered in a patient receiving ceftriaxone by intermittent IV infusion, the drugs should be given sequentially and IV infusion lines should be thoroughly flushed with a compatible infusion fluid before administering the other drug.1,2,18,30,32 Admixtures containing ceftriaxone 10 mg/mL and metronidazole hydrochloride 5-7.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection are stable for 24 hours at room temperature; however, precipitation will occur if these admixtures are refrigerated or if metronidazole concentrations greater than 8 mg/mL are used.1,2,18,32

Ceftriaxone is incompatible with calcium-containing diluents or solutions (e.g. Ringer's/lactated Ringer's solution, Hartmann's solution); particulate formation can result if the drug is admixed with calcium-containing diluents or solutions.1,2,18,30,32

Specialized references should be consulted for specific compatibility information.1

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

cefTRIAXone Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

250 mg (of ceftriaxone)*

cefTRIAXone for Injection

500 mg (of ceftriaxone)*

cefTRIAXone for Injection

1 g (of ceftriaxone)*

cefTRIAXone for Injection

2 g (of ceftriaxone)*

cefTRIAXone for Injection

For injection, for IV infusion

1 g (of ceftriaxone)*

cefTRIAXone ADD-Vantage®

Hospira

cefTRIAXone for Injection, for IV Infusion (available in dual-chambered Duplex® drug delivery system with 3.74% dextrose injection)

B Braun

cefTRIAXone for Injection, for IV Infusion

2 g (of ceftriaxone)*

cefTRIAXone ADD-Vantage®

Hospira

cefTRIAXone for Injection, for IV Infusion (available in dual-chambered Duplex® drug delivery system with 2.22% dextrose injection)

B Braun

cefTRIAXone for Injection for IV Infusion

10 g (of ceftriaxone) pharmacy bulk package*

cefTRIAXone for Injection, for IV Infusion

100 g (of ceftriaxone) pharmacy bulk package*

cefTRIAXone for Injection, for IV Infusion

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

cefTRIAXone Sodium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

20 mg (of ceftriaxone) per mL (1 g) in 3.8% Dextrose*

cefTRIAXone Iso-osmotic in Dextrose Injection (Galaxy® [Baxter])

40 mg (of ceftriaxone) per mL (2 g) in 2.4% Dextrose*

cefTRIAXone Iso-osmotic in Dextrose Injection (Galaxy® [Baxter])

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions October 1, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

1. Hospira, Inc. Ceftriaxone sodium injection powder, for solution prescribing information. Lake Forest, IL; 2017 Jun.

2. Apotex Corporation. Ceftriaxone injection, powder, for solution prescribing information. Weston, FL; 2017 Sep.

3. B Braun Medical Inc. Ceftriaxone for injection and dextrose injection in Duplex® container, for intravenous use prescribing information. Bethlehem, PA; 2015 Jul.

4. Hall MJ, Westmacott D, Wong-Kai-In P. Comparative in-vitro activity and mode of action of ceftriaxone (Ro 13-9904), a new highly potent cephalosporin. J Antimicrob Chemother . 1981; 8:193-203. [PubMed 6270051]

5. Livermore DM, Williams RJ, Williams JD. Comparison of the β-lactamase stability and the in-vitro activity of cefoperazone, cefotaxime, cefsulodin, ceftazidime, moxalactam and ceftriaxone against Pseudomonas aeruginosa . J Antimicrob Chemother . 1981; 8:323-31. [PubMed 6271726]

6. Pierson CL, Schaberg DR, Fekety FR et al. In-vitro activity of SCH 29482, MK 0787, ceftriaxone and seven other antimicrobials against 840 separate clinical isolates. J Antimicrob Chemother . 1982; 9(Suppl C):79-89. [PubMed 6277844]

7. Shannon K, King A, Warren C et al. In vitro antibacterial activity and susceptibility of the cephalosporin Ro 13-9904 to beta-lactamases. Antimicrob Agents Chemother . 1980; 18:292-8. [PubMedCentral][PubMed 6969574]

8. Rolfe RD, Finegold SM. Comparative in vitro activity of ceftriaxone against anaerobic bacteria. Antimicrob Agents Chemother . 1982; 22:338-41. [PubMedCentral][PubMed 6100430]

9. Bradsher RW, Ulmer WC. Beta-lactam antibiotic susceptibility of bacteria responsible for neonatal meningitis. Chemotherapy . 1983; 29:213-7. [PubMed 6409519]

10. Dibb WL, Kjellevold VA, Digranes A. Pseudomonas aeruginosa and Acinetobacter calcoaceticus : in vitro susceptibility of 150 clinical isolates to five β-lactam antibiotics and tobramycin. Chemotherapy . 1983; 29:332-6. [PubMed 6311491]

11. Appelbaum PC, Tamin J, Pankuch GA et al. Susceptibility of 324 nonfermentative gram-negative rods to 6 cephalosporins and aztreonam. Chemotherapy . 1983; 29:337-44. [PubMed 6311492]

12. Sanders CC. Novel resistance selected by the new expanded-spectrum cephalosporins: a concern. J Infect Dis . 1983; 147:585-9. [PubMed 6601169]

14. Clarke AM, Zemcov SJV. Ro 13-9904 and GR 20263, two new cephalosporins with broad-spectrum activity: an in vitro comparison with other β-lactam antibiotics. J Antimicrob Chemother . 1981; 7:515-20. [PubMed 6790506]

15. Smalley DL, Hansen VR, Baselski VS. Susceptibility of Pseudomonas paucimobilis to 24 antimicrobial agents. Antimicrob Agents Chemother . 1983; 23:161-2. [PubMedCentral][PubMed 6600908]

16. Heard ML, Bawdon RE, Hemsell DL et al. Susceptibility profiles of potential aerobic and anaerobic pathogens isolated from hysterectomy patients. Am J Obstet Gynecol . 1984; 149:133-43. [PubMed 6562855]

17. Preblud SR, Gill CJ, Campos JM. Bactericidal activities of chloramphenicol and eleven other antibiotics against Salmonella spp. Antimicrob Agents Chemother . 1984; 25:327-30. [PubMedCentral][PubMed 6372681]

18. Hospira, Inc. Ceftriaxone sodium for injection (pharmacy bulk package) prescribing information. Lake Forest, IL; 2017 Jun.

19. Pollock HM, Holt J, Murray C. Comparison of susceptibilities of anaerobic bacteria to cefmenoxime, ceftriaxone, and other antimicrobial compounds. Antimicrob Agents Chemother . 1983; 23:780-3. [PubMedCentral][PubMed 6307137]

20. Wise R, Andrews JM, Danks G. Comparison of in vitro activity of FCE 22101, a new penem, with those of other β-lactam antibiotics. Antimicrob Agents Chemother . 1983; 24:909-14. [PubMedCentral][PubMed 6607032]

21. Gutmann L, Goldstein FW, Kitzis MD et al. Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 β-lactams. Antimicrob Agents Chemother . 1983; 23:248-51. [PubMedCentral][PubMed 6340602]

22. Fass RJ. Comparative in vitro activities of third-generation cephalosporins. Arch Intern Med . 1983; 143:1743-5. [PubMed 6615095]

23. Muytjens HL, van der Ros-van de Repe J. Comparative activities of 13 β-lactam antibiotics. Antimicrob Agents Chemother . 1982; 21:925-34. [PubMedCentral][PubMed 7114839]

24. Prère MF, Lefèvre JC, Lareng MB. Study of the in vitro activity of new cephalosporins on strains of Neisseria gonorrhoeae of the Toulouse region. Chemotherapy . 1981; 27(Suppl 1):15-8. [PubMed 6265158]

25. Scribner RK, Wedro MC, Weber AH et al. Activities of eight new β-lactam antibiotics and seven antibiotic combinations against Neisseria meningitidis . Antimicrob Agents Chemother . 1982; 21:678-80. [PubMedCentral][PubMed 6805425]

26. Kerbs SB, Stone JR, Berg SW et al. In vitro antimicrobial activity of eight new β-lactam antibiotics against penicillin-resistant Neisseria gonorrhoeae . Antimicrob Agents Chemother . 1983; 23:541-4. [PubMedCentral][PubMed 6407392]

27. Khan MY, Siddiqui Y, Gruninger RP. Comparative in-vitro activity of selected new β-lactam antimicrobials against Neisseria gonorrhoeae . Br J Vener Dis . 1982; 58:228-30. [PubMedCentral][PubMed 6286034]

28. Hall WH, Opfer BJ. Influence of inoculum size on comparative susceptibilities of penicillinase-positive and -negative Neisseria gonorrhoeae to 31 antimicrobial agents. Antimicrob Agents Chemother . 1984; 26:192-5. [PubMedCentral][PubMed 6435514]

29. Laferriere C, Marks MI, Welch DF. Effect of inoculum size on Haemophilus influenzae type b susceptibility to new and conventional antibiotics. Antimicrob Agents Chemother . 1983; 24:287-9. [PubMedCentral][PubMed 6605716]

30. Baxter Healthcare Corporation. Ceftriaxone sodium injection, iso-osmotic solution in dextrose prescribing information. Deerfield, IL; 2018 May.

31. Then RL, Angehrn P. Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism. Antimicrob Agents Chemother . 1982; 21:711-7. [PubMedCentral][PubMed 6808912]

32. Hospira, Inc. Ceftriaxone sodium injection, powder, for solution ADD-Vantage® vials prescribing information. Lake Forest, IL; 2015 Jul.

33. Scribner RK, Marks MI, Weber A et al. Yersinia enterocolitica : comparative in vitro activities of seven new β-lactam antibiotics. Antimicrob Agents Chemother . 1982; 22:140-1. [PubMedCentral][PubMed 7125625]

34. Bayer AS, Eisenstadt R, Morrison JO. Enhanced in vitro bactericidal activity of amikacin or gentamicin combined with three new extended-spectrum cephalosporins against cephalothin-resistant members of the family Enterobacteriaceae. Antimicrob Agents Chemother . 1984; 25:725-8. [PubMedCentral][PubMed 6331297]

35. Liebowitz LD, Ballard RC, Koornhof HJ. In vitro susceptibility and cross-resistance of South African isolates of Neisseria gonorrhoeae to 14 antimicrobial agents. Antimicrob Agents Chemother . 1982; 22:598-603. [PubMedCentral][PubMed 6817704]

36. Neu HC, Meropol NJ, Fu KP. Antibacterial activity of ceftriaxone (Ro 13-9904), a β-lactamase-stable cephalosporin. Antimicrob Agents Chemother . 1981; 29:414-23.

37. Eickhoff TC, Ehret J. Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative. Antimicrob Agents Chemother . 1981; 19:435-42. [PubMedCentral][PubMed 6264845]

38. Nasu M, Maskell JP, Williams RJ et al. In vitro activity of MK0787 ( N -formimidoyl thienamycin) and other beta-lactam compounds against Bacteroides spp. Antimicrob Agents Chemother . 1981; 20:433-6. [PubMedCentral][PubMed 6282191]

39. Verbist L, Verhaegen J. In vitro activity of Ro 13-9904, a new β-lactamase-stable cephalosporin. Antimicrob Agents Chemother . 1981; 19:222-5. [PubMedCentral][PubMed 6289726]

40. Chau PY, Ng WS, Ling J et al. In vitro susceptibility of Salmonella to various antimicrobial agents, including a new cephalosporin, Ro 13-9904. Antimicrob Agents Chemother . 1981; 19:8-11. [PubMedCentral][PubMed 7247363]

41. Greenwood D, Eley A. Activity of a new cephalosporin antibiotic, Ro 13-9904, against dense populations of selected enterobacteria. Antimicrob Agents Chemother . 1981; 19:66-71. [PubMedCentral][PubMed 7247361]

42. Ng WS, Chau PY, Arnold K. In vitro susceptibility of Haemophilus influenzae and Neisseria gonorrhoeae to Ro 13-9904 in comparison with other β-lactam antibiotics. Antimicrob Agents Chemother . 1981; 19:925-6. [PubMedCentral][PubMed 6271052]

43. Jacobs MR, Kelley R, Speck WT. Susceptibility of group B streptococci to 16 β-lactam antibiotics, including new penicillin and cephalosporin derivatives. Antimicrob Agents Chemother . 1982; 22:897-900. [PubMedCentral][PubMed 6758692]

44. Greenwood D, Eley A. Comparative antipseudomonal activity of some newer β-lactam agents. Antimicrob Agents Chemother . 1982; 21:204-9. [PubMedCentral][PubMed 6803664]

45. Eliopoulos GM, Reiszner E, Moellering RC. In vitro activity of Sch 34343 against enterococci and other gram-positive bacteria. Antimicrob Agents Chemother . 1985; 27:28-32. [PubMedCentral][PubMed 3845792]

46. Wise R, Gillett AP, Andrews JM et al. Ro 13-9904: a cephalosporin with a high degree of activity and broad antibacterial activity: an in vitro comparative study. J Antimicrob Chemother . 1980; 6:595-600. [PubMed 7410283]

47. Hart CA, Percival A. Resistance to cephalosporins among gentamicin-resistant Klebsiellae. J Antimicrob Chemother . 1982; 9:275-86. [PubMed 6979537]

48. Meyers BR, Srulevitch ES, Jacobson J et al. Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers. Antimicrob Agents Chemother . 1983; 24:812-4. [PubMedCentral][PubMed 6318657]

49. McNamara PJ, Gibaldi M, Stoeckel K. Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding. Part I. Theoretical considerations. Eur J Clin Pharmacol . 1983; 25:399-405. [PubMed 6313379]

50. McNamara PJ, Gibaldi M, Stoeckel K. Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding. Part II. Physiological significance. Eur J Clin Pharmacol . 1983; 25:407-12. [PubMed 6313380]

51. McNamara PJ, Stoeckel K, Ziegler WH. Pharmacokinetics of ceftriaxone following intravenous administration of a 3 g dose. Eur J Clin Pharmacol . 1982; 22:71-5. [PubMed 6284519]

52. Delsignore R, Baroni CM, Crotti G et al. Absolute bioavailability of ceftriaxone after intramuscular administration to healthy volunteers. Chemotherapy . 1983; 29:157-62. [PubMed 6307601]

53. Luderer JR, Patel IH, Durkin J et al. Age and ceftriaxone kinetics. Clin Pharmacol Ther . 1984; 35:19-25. [PubMed 6317271]

54. Stoeckel K, McNamara PJ, Brandt R et al. Effects of concentration-dependent plasma protein binding on ceftriaxone kinetics. Clin Pharmacol Ther . 1981; 29:650-7. [PubMed 7053242]

55. Patel IH, Chen S. Parsonnet M et al. Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother . 1981; 20:634-41. [PubMedCentral][PubMed 6275779]

56. Pollock AA, Tee PE, Patel IH et al. Pharmacokinetic characteristics of intravenous ceftriaxone in normal adults. Antimicrob Agents Chemother . 1982; 22:816-23. [PubMedCentral][PubMed 6295268]

57. Patel IH, Weinfeld RE, Konikoff J et al. Pharmacokinetics and tolerance of ceftriaxone in humans after single-dose intramuscular administration in water and lidocaine diluents. Antimicrob Agents Chemother . 1982; 21:957-62. [PubMedCentral][PubMed 6287931]

58. Salvador P, Smith RG, Weinfeld RE et al. Clinical pharmacology of ceftriaxone in patients with neoplastic disease. Antimicrob Agents Chemother . 1983; 23:583-8. [PubMedCentral][PubMed 6305263]

59. Schaad UB, Stoeckel K. Single-dose pharmacokinetics of ceftriaxone in infants and young children. Antimicrob Agents Chemother . 1982; 21:248-53. [PubMedCentral][PubMed 6280597]

60. Martin E, Koup JR, Paravicini U et al. Pharmacokinetics of ceftriaxone in neonates and infants with meningitis. J Pediatr . 1984; 105:475-81. [PubMed 6088747]

61. Del Rio M, McCracken GH, Nelson JD et al. Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis. Antimicrob Agents Chemother . 1982; 22:622-7. [PubMedCentral][PubMed 6295262]

62. Reed MD, Rekate HL, Aronoff SC et al. Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children. Clin Pharm . 1983; 2:558-63. [PubMed 6317277]

63. McCracken GH, Siegel JD, Threlkeld N et al. Ceftriaxone pharmacokinetics in newborn infants. Antimicrobial Agent Chemother . 1983; 23:341-3.

64. Steele RW, Eyre LB, Bradsher RW et al. Pharmacokinetics of ceftriaxone in pediatric patients with meningitis. Antimicrob Agents Chemother . 1983; 23:191-4. [PubMedCentral][PubMed 6301362]

65. Latif R, Dajani AS. Ceftriaxone diffusion into cerebrospinal fluid of children with meningitis. Antimicrob Agents Chemother . 1983; 23:46-8. [PubMedCentral][PubMed 6299184]

66. Kafetzis DA, Brater DC, Fanourgakis JE et al. Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum. Antimicrob Agents Chemother . 1983; 23:870-3. [PubMedCentral][PubMed 6311089]

67. Geroulanos S, Donfried B, Turina M. Plasma levels of ceftriaxone in cardiovascular surgery. Am J Surg . 1984; 148(Suppl 4A):5-7. [PubMed 6091483]

68. Bryan CS, Morgan SL, Jordan AB et al. Ceftriaxone levels in blood and tissue during cardiopulmonary bypass surgery. Antimicrob Agents Chemother . 1984; 25:37-9. [PubMedCentral][PubMed 6322680]

69. Maudgal DP, Maxwell JD, Lees LJ et al. Biliary excretion of amoxycillin and ceftriaxone after intravenous administration in man. Br J Clin Pharmacol . 1982; 14:213-7. [PubMedCentral][PubMed 6285946]

70. Axelrod JL, Newton JC, Sarakhun C et al. Ceftriaxone: a new cephalosporin with aqueous humor levels effective against Enterobacteriaceae. Arch Ophthalmol . 1985; 103:71-2. [PubMed 3977680]

71. Daschner FD, Petersen EE, Brandle J et al. Concentrations of ceftriaxone in serum and gynecological tissues. Chemotherapy . 1983; 29:153-5. [PubMed 6301774]

72. Arvidsson A, Alvan G, Angelin B et al. Ceftriaxone: renal and biliary excretion and effect on the colon microflora. J Antimicrob Chemother . 1982; 10:207-15. [PubMed 6292158]

73. Cohen D, Appel GB, Scully B et al. Pharmacokinetics of ceftriaxone in patients with renal failure and in those undergoing hemodialysis. Antimicrob Agents Chemother . 1983; 24:529-32. [PubMedCentral][PubMed 6316845]

74. Stoeckel K, McNamara PJ, Hoppe-Seyler G et al. Single-dose ceftriaxone kinetics in functionally anephric patients. Clin Pharmacol Ther . 1983; 33:633-41. [PubMed 6301740]

75. Ti TY, Fortin L, Kreeft JH et al. Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis. Antimicrob Agents Chemother . 1984; 24:83-7.

76. Stoeckel K, Tuerk H, Trueb V et al. Single-dose ceftriaxone kinetics in liver insufficiency. Clin Pharmacol Ther . 1984; 36:500-9. [PubMed 6090050]

77. Patel IH, Sugihara JG, Weinfeld RE et al. Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment. Antimicrob Agents Chemother . 1984; 25:438-42. [PubMedCentral][PubMed 6329080]

78. Thabaut A, Durosoir JL, Saliou P. Comparative in vitro activity of 8 cephalosporins on 109 strains of Neisseria gonorrhoeae and 60 strains of Neisseria meningitidis . Chemotherapy . 1981; 27(Suppl 1):19-24. [PubMed 6265159]

79. Then RL. Properties of Ro 13-9904 as a substrate and inhibitor of β-lactamases. Chemotherapy . 1981; 27(Suppl 1):25-31. [PubMed 6972858]

80. Cadoz M, Denis F, Felix H et al. Treatment of purulent meningitis with a new cephalosporin—Rocephin® (Ro 13-9904): clinical, bacteriological and pharmacological observations in 24 cases. Chemotherapy . 1981; 27(Suppl 1):57-61. [PubMed 7249796]

81. Eichmann A, Weidmann G, Havas L. One-dose treatment of acute uncomplicated gonorrhoea of male patients with ceftriaxone Ro 13-9904, a new parenteral cephalosporin: a dose-range finding pilot study using doses of 500, 250, 125 and 50 mg respectively, in descending order. Chemotherapy . 1981; 27(Suppl 1):62-9. [PubMed 6788458]

82. Giamarellou H, Poulopoulos B, Katsabas A et al. Antibacterial activity of Ro 13-9904 and preliminary experience in gonorrhoea and chronic urinary tract infections. Chemotherapy . 1981; 27(Suppl 1):70-4. [PubMed 7018852]

83. Squires E, Cleeland R, Christenson J et al. Interpretation of susceptibility testing of ceftriaxone. Am J Med . 1984; 77(Suppl 4C):12-6. [PubMed 6093512]

84. Patel IH, Kaplan SA. Pharmacokinetic profile of ceftriaxone in man. Am J Med . 1984; 77(Suppl 4C):17-25. [PubMed 6093513]

85. Stoeckel K, Koup JR. Pharmacokinetics of ceftriaxone in patients with renal and liver insufficiency and correlations with a physiologic nonlinear protein binding model. Am J Med . 1984; 77(Suppl 4C):26-32. [PubMed 6093514]

86. Scheld WM, Rocha H, Sande MA et al. Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis. Am J Med . 1984; 77(Suppl 4C):42-9. [PubMed 6093518]

87. Steele RW. Ceftriaxone therapy of meningitis and serious infections. Am J Med . 1984; 77(Suppl 4C):50-3. [PubMed 6093519]

88. Baumgartner JD, Glauser MP. Tolerance study of ceftriaxone compared with amoxicillin in patients with pneumonia. Am J Med . 1984; 77(Suppl 4C):54-8. [PubMed 6093520]

89. Bradsher RW, Snow RM. Ceftriaxone treatment of skin and soft tissue infections in a once daily regimen. Am J Med . 1984; 77(Suppl 4C):63-7. [PubMed 6093522]

90. Collier AC, Judson FN, Murphy VL et al. Comparative study of ceftriaxone and spectinomycin in treatment of uncomplicated gonorrhea in women. Am J Med . 1984; 77(Suppl 4C):68-72. [PubMed 6093523]

91. Childs SJ, Wells WG, Mirelman S. Ceftriaxone for once-a-day therapy of urinary tract infections. Am J Med . 1984; 77(Suppl 4C):73-6. [PubMed 6093524]

92. Moskovitz BL. Clinical adverse effects during ceftriaxone therapy. Am J Med . 1984; 77(Suppl 4C):84-8. [PubMed 6093526]

93. Oakes M, MacDonald H, Wilson D. Abnormal laboratory test values during ceftriaxone therapy. Am J Med . 1984; 77(Suppl 4C):89-96. [PubMed 6093527]

94. Mannion JC, Bloch R, Popovich NG. Cephalosporin-aminoglycoside synergistic nephrotoxicity: fact of fiction? Drug Intell Clin Pharm . 1981; 15:248-56.

95. Haubenstock A, Schmidt P, Zazgornik J et al. Hypoprothrombinaemic bleeding associated with ceftriaxone. Lancet . 1983; 1:1215-6. [PubMed 6134007]

96. Meatherall RC, Guay DR, Baxter H. Cephalosporins and urinary protein determination. Clin Chem . 1985; 31:165. [PubMed 3965206]

97. LeBel M, Paone RP, Lewis GP. Lack of interference of five new beta-lactam antibiotics with serum creatinine determination. Drug Intell Clin Pharm . 1983; 17:908-10. [PubMed 6317326]

98. Guay DRP, Meatherall RC, Macaulay PA. Interference of selected second- and third-generation cephalosporins with creatinine determination. Am J Hosp Pharm . 1983; 40:435-8. [PubMed 6846351]

99. Gannon RH, Levy RM. Interference of third-generation cephalosporins with theophylline assay by high-performance liquid chromatography. Am J Hosp Pharm . 1984; 41:1185-6. [PubMed 6331158]

100. LeBel M, Paone RP, Lewis GP. Effect of ten new β-lactam antibiotics on urine glucose test methods. Drug Intell Clin Pharm . 1984; 18:617-20. [PubMed 6745089]

101. Fass RJ. Comparative in vitro activities of β-lactam-tobramycin combinations against Pseudomonas aeruginosa and multidrug-resistant gram-negative enteric bacilli. Antimicrob Agents Chemother . 1982; 21:1003-6. [PubMedCentral][PubMed 6810755]

102. Watanakunakorn C. In vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa. Antimicrob Agents Chemother . 1983; 24:305-6. (IDIS 174922)

103. Hooton TM, Blair AD, Turck M et al. Synergism at clinically attainable concentrations of aminoglycoside and β-lactam antibiotics. Antimicrob Agents Chemother . 1984; 26:535-8. [PubMedCentral][PubMed 6517544]

104. Richards DM, Heel RC, Brogden RN et al. Ceftriaxone: a review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs . 1984; 27:469-527. [PubMed 6329638]

105. Barriere SL, Flaherty JF. Third-generation cephalosporins: a critical evaluation. Clin Pharm . 1984; 3:351-73. [PubMed 6432420]

106. Neu HC. The new beta-lactamase-stable cephalosporins. Ann Intern Med . 1982; 97:408-19. [PubMed 6810737]

107. Garzone P, Lyon J, Yu VL. Third-generation and investigational cephalosporins: I. Structure-activity relationships and pharmacokinetic review. Drug Intell Clin Pharm . 1983; 17:507-15. [PubMed 6347596]

108. Garzone P, Lyon J, Yu VL. Third-generation and investigational cephalosporins: II. Microbiologic review and clinical summaries. Drug Intell Clin Pharm . 1983; 17:615-22. [PubMed 6311502]

109. Bradley JS, Connor JD. Ceftriaxone failure in meningitis caused by Streptococcus pneumoniae with reduced susceptibility to beta-lactam antibiotics. Pediatr Infect Dis J . 1991; 10:871-3. [PubMed 1749702]

110. Thompson RL, Wright AJ. Cephalosporin antibiotics. Mayo Clin Proceed . 1983; 58:79-87.

111. Paris MM, Ramilo I, McCracken GH. Management of meningitis caused by penicillin-resistant Streptococcus pneumoniae . Antimicrob Agents Chemother . 1995; 2171-5.

114. Zajdowicz TR, Sanches PL, Berg SW et al. Comparison of ceftriaxone with cefoxitin in the treatment of penicillin-resistant gonococcal urethritis. Br J Vener Dis . 1983; 59:176-8. [PubMedCentral][PubMed 6303490]

115. Handsfield HH, Murphy VL, Holmes KK. Dose-ranging study of ceftriaxone for uncomplicated gonorrhea in men. Antimicrob Agents Chemother . 1981; 20:839-40. [PubMedCentral][PubMed 6275788]

116. Handsfield HH, Murphy VL. Comparative study of ceftriaxone and spectinomycin for treatment of uncomplicated gonorrhoea in men. Lancet . 1983; 2:67-70. [PubMed 6134959]

117. Judson FN, Ehret JM, Root CJ. Comparative study of ceftriaxone and aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in women. Antimicrob Agents Chemother . 1983; 23:218-20. [PubMedCentral][PubMed 6301364]

118. Judson FN, Ehret JM, Handsfield HH. Comparative study of ceftriaxone and spectinomycin for treatment of pharyngeal and anorectal gonorrhea. JAMA . 1985; 253:1417-9. [PubMed 3155806]

119. Maslow MJ, Levine JF, Pollock AA et al. Efficacy of a twelve-hourly ceftriaxone regimen in the treatment of serious bacterial infections. Antimicrob Agents Chemother . 1982; 22:103-7. [PubMedCentral][PubMed 6289735]

120. Scully BE, Neu HC. Ceftriaxone in the treatment of serious infections, particularly after surgery. Am J Surg . 1984; 148(Suppl 4A):35-40. [PubMed 6091479]

121. Eron LJ, Park CH, Goldenberg RI et al. Ceftriaxone therapy of serious bacterial infections. J Antimicrob Chemother . 1983; 12:65-78. [PubMed 6311783]

122. Harrison CJ, Welch D, Marks MI. Ceftriaxone therapy in pediatric patients. Am J Dis Child . 1983; 137:1048-51. [PubMed 6314806]

123. Steele RW, Bradsher RW. Ceftriaxone for the treatment of serious infections. Am J Dis Child . 1983; 137:1044-7. [PubMed 6314805]

124. Aronoff SC, Murdell D, 0'Brien CA et al. Efficacy and safety of ceftriaxone in serious pediatric infections. Antimicrob Agents Chemother . 1983; 24:663-6. [PubMedCentral][PubMed 6318653]

125. Baumgartner JD, Glauser MP. Single daily dose treatment of severe refractory infections with ceftriaxone: cost savings and possible parenteral outpatient treatment. Arch Intern Med . 1983; 143:1868-73. [PubMed 6312914]

126. Poretz DM, Eron LJ, Goldenberg RI et al. Intravenous antibiotic therapy in an outpatient setting. JAMA . 1982; 248:336-9. [PubMed 7087128]

127. Bradsher RW. Ceftriaxone (Ro 13-9904) therapy of serious infection. Antimicrob Agents Chemother . 1982; 22:36-42. [PubMedCentral][PubMed 6289739]

128. Gnann JW, Goetter WE, Elliott AM et al. Ceftriaxone: in vitro studies in clinical evaluation. Antimicrob Agents Chemother . 1982; 22:1-9. [PubMedCentral][PubMed 6289734]

129. Epstein JS, Hasslequist SM, Simon GL. Efficacy of ceftriaxone in serious bacterial infections. Antimicrob Agents Chemother . 1982; 21:402-6. [PubMedCentral][PubMed 6285809]

130. Chadwick EG, Connor EM, Shulman ST et al. Efficacy of ceftriaxone in treatment of serious childhood infections. J Pediatr . 1983; 103:141-5. [PubMed 6306193]

131. Bittner MJ, Dworzack DL, Preheim LC et al. Ceftriaxone therapy of serious bacterial infections in adults. Antimicrob Agents Chemother . 1983; 23:261-6. [PubMedCentral][PubMed 6301365]

132. Eron LJ, Park CH, Hixon DL et al. Ceftriaxone therapy of bone and soft tissue infections in hospital and outpatient settings. Antimicrob Agents Chemother . 1983; 23:731-7. [PubMedCentral][PubMed 6307135]

133. Tauber MG, Sande MA. Principles in the treatment of bacterial meningitis. Am J Med . 1984; 76(Suppl 5A):224-30. [PubMed 6372474]

134. McCracken GH. Management of bacterial meningitis: current status and future prospects. Am J Med . 1984; 76(Suppl 5A):215-23. [PubMed 6372473]

135. Fulginiti VA. Treatment of meningitis in the very young infant. Am J Dis Child . 1983; 137:1043. [PubMed 6637905]

136. Enzenauer RW, Bass JW. Initial antibiotic treatment of purulent meningitis in infants 1 to 2 months of age. Am J Dis Child . 1983; 137:1055-6. [PubMed 6605679]

137. Baumgartner ET, Augustine A, Steele RW. Bacterial meningitis in older neonates. Am J Dis Child . 1983; 137:1052-4. [PubMed 6356881]

138. Shaw DW, Ali RM, Beeching NJ et al. Ceftriaxone for meningitis, due to Escherichia coli , which developed during tobramycin therapy. N Z Med J . 1984; 97:500. [PubMed 6089061]

139. Aronoff SC, Reed MD, O'Brien CA et al. Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis. J Antimicrob Chemother . 1984; 13:143-51. [PubMed 6323376]

140. Congeni BL. Comparison of ceftriaxone and traditional therapy of bacterial meningitis. Antimicrob Agents Chemother . 1984; 25:40-4. [PubMedCentral][PubMed 6322681]

141. Chadwick EG, Yogev R, Shulman ST et al. Single-dose ceftriaxone pharmacokinetics in pediatric patients with central nervous system infections. J Pediatr . 1983; 102:134-7. [PubMed 6294263]

142. Steele RW, Bradsher RW. Comparison of ceftriaxone with standard therapy for bacterial meningitis. J Pediatr . 1983; 103:138-41. [PubMed 6306192]

143. Del Rio MD, Chrane D, Shelton S et al. Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. Lancet . 1983; 1:1241-4. [PubMed 6134039]

144. Martin E. Ceftriaxone for meningitis. Lancet . 1983; 2:43-4.

145. Eng RH, Cherubin C, Smith SM et al. Examination of gram-negative bacilli from meningitis patients who failed or relapsed on moxalactam therapy. Antimicrob Agents Chemother . 1984; 26:850-6. [PubMedCentral][PubMed 6395799]

146. Judson FN, Ehret JM. Single-dose ceftriaxone to eradicate pharyngeal Neisseria meningitidis . Lancet . 1984; 2:1462-3. [PubMed 6151066]

147. Harnoss BM, Hirner A, Kruselmann M et al. Antibiotic infection prophylaxis in gallbladder surgery—a prospective randomized study. Chemotherapy . 1985; 31:76-82. [PubMed 3882356]

148. Childs SJ, Wells WG, Mirelman S. Antibiotic prophylaxis for genitourinary surgery in community hospitals. J Urol . 1983; 130:305-8. [PubMed 6308283]

149. Stone HH, Mullins RJ, Strom PR et al. Ceftriaxone versus combined gentamicin and clindamycin for polymicrobial surgical sepsis. Am J Surg . 1984; 148(Suppl 4A):30-4. [PubMed 6091478]

150. Eron LJ, Goldenberg RI, Poretz DM. Combined ceftriaxone and surgical therapy for osteomyelitis in hospital and outpatient settings. Am J Surg . 1984; 148(Suppl 4A):1-4. [PubMed 6091473]

151. Beam TR, Raab TA, Spooner JA et al. Comparison of ceftriaxone and cefazolin prophylaxis against infection in open heart surgery. Am J Surg . 1984; 148(Suppl 4A):8-14. [PubMed 6091484]

152. Kellum JM, Gargano S, Gorbach SL et al. Antibiotic prophylaxis in high-risk biliary operations: multicenter trial of single preoperative ceftriaxone versus multidose cefazolin. Am J Surg . 1984; 148(Suppl 4A):15-8. [PubMed 6091474]

153. Meyer JM. Comparative study of ceftriaxone and cefuroxime for perioperative prophylaxis in orthopedic surgery. Am J Surg . 1984; 148(Suppl 4A):27-9. [PubMed 6091477]

154. Hemsell DL, Menon MO, Friedman AJ. Ceftriaxone or cefazolin prophylaxis for the prevention of infection after vaginal hysterectomy. Am J Surg . 1984; 148(Suppl 4A):22-6. [PubMed 6091476]

155. Finkelstein LH, Arsht DB, Manfrey SJ et al. Ceftriaxone in the prevention of postoperative infection in patients undergoing transurethral resection of the prostate. Am J Surg . 1984; 148(Suppl 4A):19-21. [PubMed 6091475]

156. Siegel JD, McCracken GH. Sepsis neonatorum N Engl J Med . 1981; 304:642-7.

157. Adam D, Naber KG. Concentrations of ceftriaxone in prostate adenoma tissue. Chemotherapy . 1984; 20:1-6.

158. Just HM, Beckert A, Bassler M et al. Combination effect of ceftriaxone with four aminoglycosides on nonfermenting gram-negative bacteria. Chemotherapy . 1982; 28:397-401. [PubMed 6291869]

159. Just HM, Frank U, Simon A et al. Concentrations of ceftriaxone in serum and lung tissue. Chemotherapy . 1984; 30:81-3. [PubMed 6321115]

160. Barza M. Three generations of cephalosporins. Clin Pharm . 1982; 1:165-6.

161. Goldstein EJ, Citron DM. Susceptibility of Eikenella corrodens to penicillin, apalcillin, and twelve new cephalosporins. Antimicrob Agents Chemother . 1984; 26:947-8. [PubMedCentral][PubMed 6395802]

162. Brogard JM, Comte F. Pharmacokinetics of the new cephalosporins. Antibiot Chemother (Basel) . 1982; 31:145-210.

163. Food and Drug Administration. Antibiotic drugs; sterile ceftriaxone sodium (Docket No. 85N-0011). Fed Regist . 1985; 50:9998-10001.

164. Burnakis TG. Surgical antimicrobial prophylaxis: principles and guidelines. Pharmacotherapy . 1984; 4:248-71. [PubMed 6438611]

165. Webber JA, Wheeler WJ. Antimicrobial and pharmacokinetic properties of newer penicillins and cephalosporins. In: Morin RB, Gorman M, eds. Chemistry and biology of β-lactam antibiotics. New York, NY: Academic Press; 1982:372-427.

166. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 13th ed. Washington DC: Public Health Foundation; 2015. Available at CDC website. [Web]

167. Acharya G, Butler T, Ho M et al. Treatment of typhoid fever: randomized trial of a three-day course of ceftriaxone versus a fourteen-day course of chloramphenicol. Am J Trop Med Hyg . 1995; 52:162-5. [PubMed 7872445]

169. Gould IM, Wise R. Third generation cephalosporins. BMJ . 1985; 1:878-9.

170. Balant L, Dayer P, Auckenthaler R. Clinical pharmacokinetics of the third generation cephalosporins. Clin Pharmacokinet . 1985; 10:101-43. [PubMed 3888488]

171. Reiner R, Weiss U, Brombacher U et al. Ro 13-9904/001, a novel potent and long-acting parenteral cephalosporin. J Antibiot . 1980; 33:783-6. [PubMed 6967869]

172. Seddon M, Wise R, Gillett AP et al. Pharmacokinetics of Ro 13-9904, a broad-spectrum cephalosporin. Antimicrob Agents Chemother . 1980; 18:240-2. [PubMedCentral][PubMed 7447404]

173. Johnson RC, Bey RF, Wolgamot SJ. Comparison of the activities of ceftriaxone and penicillin G against experimentally induced syphilis in rabbits. Antimicrob Agents Chemother . 1982; 21:984-9. [PubMedCentral][PubMed 6287932]

174. Knothe H, Dette GA. The current state of cephalosporin antibiotics: microbiological aspects. Infection . 1983; 11(Suppl 1):S12-15. [PubMed 6601063]

175. Neu HC. Cephalosporin antibiotics as applied in surgery of bones and joints. Clin Orthop . 1984; 190:50-64.

176. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull . 1982; 12:10-1. [PubMed 7188569]

177. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics . 1983; 72:356-8. [PubMed 6889041]

178. Schaad UB, Hayton WL, Stoeckel K. Single-dose ceftriaxone kinetics in the newborn. Clin Pharmacol Ther . 1985; 37:522-8. [PubMed 3987175]

179. Reviewers' comments (personal observations).

181. Hornstein MJ, Jupeau AM, Scavizzi MR et al. In vitro susceptibilities of 126 clinical isolates of Yersinia enterocolitica to 21 β-lactam antibiotics. Antimicrob Agents Chemother . 1985; 27:806-11. [PubMedCentral][PubMed 2990327]

182. Ettlin R, Hoigné R, Bruppacher R et al. Atopy and adverse drug reactions. Int Arch Allergy Appl Immunol . 1981; 66(Suppl 1):93-5.

183. Patterson R. Allergic reactions to drugs and biological agents. JAMA . 1982; 248:2637-45. [PubMed 7143626]

184. Hoigné R, Hopf B, Sonntag R. Penicillins, cephalosporins and tetracyclines. In: Dukes MNG, ed. Meyler's side effects of drugs. 9th ed. New York: Elsevier/North Holland Inc; 1980:411-22.

186. Loveless MO, Ross AK, Jackson JM et al. Double-blind human volunteer study of the influence of ceftriaxone and moxalactam on platelet function. Program and abstracts of the twenty-fourth Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: Oct 1984. Abstract No. 962.

187. Lin T, Chrane DF, Nelson JD et al. Seven days of ceftriaxone therapy is as effective as 10 days' treatment for bacterial meningitis. JAMA . 1985; 253:3559-63. [PubMed 3889396]

188. Girgis NI, Sultan Y, Hammad O et al. Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children. Pediatr Infect Dis J . 1995; 14:603-5. [PubMed 7567290]

189. Anon. Chancroid detected by polymerase chain reaction—Jackson, Mississippi, 1994-1995. MMWR Morb Mortal Wkly Rep . 1995; 44:567,573-4. [PubMed 7616954]

190. Wenzel RP. Preoperative antibiotic prophylaxis. N Engl J Med . 1992; 326:337-9. [PubMed 1728738]

192. Brogden RN, Ward A. Ceftriaxone: a reappraisal of its antibacterial activity and pharmacokinetic properties, and an update on its therapeutic use with particular reference to once-daily administration. Drugs . 1988; 35:604-45. [PubMed 3048974]

197. Anon. Drugs for bacterial infections. Med Lett Treat Guid . 2010; 8:43-52.

202. Tyndall M, Malisa M, Plummer FA et al. Ceftriaxone no longer predictably cures chancroid in Kenya. J Infect Dis . 1993; 167:469-71. [PubMed 8421184]

203. Jones RN, Barry AL. Antimicrobial activity of ceftriaxone, cefotaxime, desacetylcefotaxime, and cefotaxime-desacetylcefotaxime in the presence of human serum. Antimicrob Agents Chemother . 1987; 31:818-20. [PubMedCentral][PubMed 3606081]

204. Le Saux N, Slaney LA, Plummer FA et al. In vitro activity of ceftriaxone, cefetamet (Ro 15-8074), ceftetrame (Ro 19-5247; T-2588), and fleroxacin (Ro 23-6240; AM-833) versus Neisseria gonorrhoeae and Haemophilus ducreyi . Antimicrob Agents Chemother . 1987; 31:1153-4. [PubMedCentral][PubMed 2959199]

205. Hamilton RA, Kowalsky SF, McCormick EM et al. Protein binding of ceftriaxone, cefoperazone, and ceftizoxime. Clin Pharm . 1987; 6:567-9. [PubMed 3480089]

206. Powell KR, Mawhorter SD. Outpatient treatment of serious infections in infants and children with ceftriaxone. J Pediatr . 1987; 111:898-901.

207. Dattwyler RJ, Halperin JJ, Pass H et al. Ceftriaxone as effective therapy in refractory Lyme disease. J Infect Dis . 1987; 155:1322-5. [PubMed 3572042]

209. Schaad UB, Tschappeler H, Lentze MJ. Transient formation of precipitations in the gallbladder associated with ceftriaxone therapy. Pediatr Infect Dis . 1986; 5:708-10. [PubMed 3540889]

210. Bowmer MI, Nsanze H, D'Costa LJ et al. Single-dose ceftriaxone for chancroid. Antimicrob Agents Chemother . 1987; 31:67-9. [PubMedCentral][PubMed 3566241]

211. Schmid GP. The treatment of chancroid. JAMA . 1986; 255:1757-62. [PubMed 3512872]

212. Baxter Healthcare Corporation. Descriptive information on premixed frozen products. Deerfield, IL; 1992 Sep.

213. Hammerschlag MR, Gleyzer A. In vitro activity of a group of broad-spectrum cephalosporins and other β-lactam antibiotics against Chlamydia trachomatis . Antimicrob Agents Chemother . 1983; 23:493-4. [PubMedCentral][PubMed 6847175]

214. Muytjens HL, Heessen FW. In vitro activities of thirteen β-lactam antibiotics against Chlamydia trachomatis . Antimicrob Agents Chemother . 1982; 22:520-1. [PubMedCentral][PubMed 7137988]

215. Agnelli G, Del Favero A, Parise P et al. Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit? Antimicrob Agents Chemother . 1986; 29:1108-9.

216. Moorthy TT, Lee CT, Lim KB et al. Ceftriaxone for treatment of primary syphilis in men: a preliminary study. Sex Transm Dis . 1987; 14:116-8. [PubMed 3616852]

217. Guerrant RL, Gilder TV, Steiner TS et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis . 2001; 32:331-50. [PubMed 11170940]

218. Grimes DA, Bount JH, Patrick J et al. Antibiotic treatment of pelvic inflammatory disease: trends among private physicians in the United States, 1966 through 1983. JAMA . 1986; 256:3223-6. [PubMed 3783865]

219. Laga M, Naamara W, Brunham RC et al. Single-dose therapy of gonococcal ophthalmia neonatorum with ceftriaxone. N Engl J Med . 1986; 315:1382-5. [PubMed 3095641]

220. Haase DA, Nash RA, Nsanze H et al. Single-dose ceftriaxone therapy of gonococcal ophthalmia neonatorum. Sex Transm Dis . 1986; 13:53-5. [PubMed 3082022]

221. Miller DW, Shove GA, Jones T et al. Disseminated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae —Wisconsin, Pennsylvania. MMWR Morb Mortal Wkly Rep . 1987; 36:161-2,167. [PubMed 3102922]

222. Sanders LL, Harrison HR, Washington AE. Treatment of sexually transmitted chlamydial infections. JAMA . 1986; 255:1750-6. [PubMed 3512871]

224. Lisby SM, Nahata MC. Recognition and treatment of chlamydial infections. Clin Pharm . 1987; 6:25-36. [PubMed 3545650]

225. Judson FN. Treatment of uncomplicated gonorrhea with ceftriaxone: a review. Sex Transm Dis . 1986; 13(Suppl):199-202. [PubMed 3094173]

227. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance. A report from the drug-resistant Streptococcus pneumoniae therapeutic working group. Arch Intern Med . 2000; 160:1399-1408. [PubMed 10826451]

228. Marra CM, Boutin P, McArthur JC et al. A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis . 2000; 30:540-4. [PubMed 10722441]

229. Taylor DN, Pitarangsi C, Echeverria P et al. Comparative study of ceftriaxone and trimethoprim-sulfamethoxazole for the treatment of chancroid in Thailand. J Infect Dis . 1985; 152:1002-6. [PubMed 3876396]

230. Douglas J, Judson F, Spencer N et al. Multiple strain outbreak of penicillinase-producing Neisseria gonorrhoeae —Denver, Colorado, 1986. MMWR Morb Mortal Wkly Rep . 1987; 36:534-6,542-3. [PubMed 2956495]

231. Centers for Disease Control Gonococcal Isolate Surveillance Project. Sentinel surveillance system for antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae . MMWR Morb Mortal Wkly Rep . 1987; 36:585-6,591-3. [PubMed 3114604]

232. Knapp JS, Zenilman JM, Biddle JW et al. Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid-mediated, high-level resistance to tetracycline. J Infect Dis . 1987; 155:819-22. [PubMed 3102635]

233. Bowie WR, Shaw CE, Chan DGW et al. In-vitro susceptibility of 400 isolates of Neisseria gonorrhoeae in Vancouver, 1982-84. CMAJ . 1986; 135:489-93. [PubMedCentral][PubMed 3091234]

234. Carson R, Tasker E, Houle B et al. Tetracycline-resistant Neisseria gonorrhoeae —Georgia, Pennsylvania, New Hampshire. MMWR Morb Mortal Wkly Rep . 1985; 34:563-4,569-70. [PubMed 3929060]

235. Brewer F, Matuszak DL, Libonati JP et al. Tetracycline-resistant Neisseria . N Engl J Med . 1986; 315:1548-9. [PubMed 3097541]

236. Kaiser AB. Antimicrobial prophylaxis in surgery. N Engl J Med . 1986; 315:1129-38. [PubMed 3531863]

237. Gulian JM, Gonard V, Dalmasso C et al. Bilirubin displacement by ceftriaxone in neonates: evaluation by determination of "free' bilirubin and erythrocyte-bound bilirubin. J Antimicrob Chemother . 1987; 19:823-9. [PubMed 3610909]

238. Gulian JM, Dalmasso C, Pontier C et al. Displacement effect of ceftriaxone on bilirubin bound to human serum albumin. Chemotherapy . 1986; 32:399-403. [PubMed 3757585]

239. Zenilman JM, Nims LJ, Menegus MA et al. Spectinomycin-resistant gonococcal infections in the United States, 1985-1986. J Infect Dis . 1987; 158:1002-4.

240. Boslego JW, Tramont EC, Takafuji ET et al. Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae . N Engl J Med . 1987; 317:272-8. [PubMed 2955222]

241. Schulte JM, Schmid GP. Recommendations for treatment of chancroid, 1993. Clin Infect Dis . 1995; 20(Suppl 1):S39-46.

242. Pallares R, Linares J, Vadillo M et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med . 1995; 333:474-80. [PubMed 7623879]

243. American Academy of Pediatrics Committee on Infectious Diseases. Therapy for children with invasive pneumococcal infections. Pediatrics . 1997; 99:289-99. [PubMed 9024464]

244. Jacobs RF, Wright MW, Deskin RL et al. Delayed sterilization of Haemophilus influenzae type b meningitis with twice-daily ceftriaxone. JAMA . 1988; 259:392-4. [PubMed 3257278]

245. McCarthy CA, Powell KR. Single- vs divided-dose ceftriaxone therapy for meningitis. JAMA . 1988; 260:925. [PubMed 3398195]

246. Frenkel LD, Multicenter Ceftriaxone Pediatric Study Group. Once-daily administration of ceftriaxone for treatment of selected serious bacterial infections in children. Pediatrics . 1988; 82(3 Part 2):486-91. [PubMed 3405685]

247. Meyboom RHB, Kuiper H, Jansen A. Ceftriaxone and reversible cholelithiasis. BMJ . 1988; 297:858. [PubMedCentral][PubMed 3140956]

248. Schaad UB, Wedgwood-Krucko J, Tschaeppeler H. Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet . 1988; 2:1411-3. [PubMed 2904533]

249. Congeni BL, Bradley J, Hammerschlag MR. Safety and efficacy of once daily ceftriaxone for the treatment of bacterial meningitis. Pediatr Infect Dis . 1986; 5:293-7. [PubMed 3088548]

250. Yogev R, Shulman ST, Chadwick EG et al. Once daily ceftriaxone for central nervous system infections and other serious pediatric infections. Pediatr Infect Dis . 1986; 5:298-303. [PubMed 3725639]

251. Judson FN. Management of antibiotic-resistant Neisseria gonorrhoeae . Ann Intern Med . 1989; 110:5-7. [PubMed 2491746]

252. Boslego JW, Tramont EC. Spectinomycin and resistant Neisseria gonorrhoeae . N Engl J Med . 1988; 318:326. [PubMed 3336429]

253. Zenilman JM, Nims LJ, Menegus MA et al. Spectinomycin-resistant gonococcal infections in the United States, 1985-1986. J Infect Dis . 1987; 156:1002-4. [PubMed 2960748]

254. Easmon CSF, Ison CA, Woodford N. Spectinomycin and resistant Neisseria gonorrhoeae . N Engl J Med . 1988; 318:325-6. [PubMed 2961996]

255. Jacobs RF. Ceftriaxone-associated cholecystitis. Pediatr Infect Dis J . 1988; 7:434-6. [PubMed 3293002]

256. Jacobs RF, Kearns GL. Single- vs divided-dose ceftriaxone therapy for meningitis. JAMA . 1988; 260:925-6.

257. Dankner WM, Connor JD, Sawyer M et al. Treatment of bacterial meningitis with once daily ceftriaxone therapy. J Antimicrob Chemother . 1988; 21:637-45. [PubMed 3391863]

258. Tuncer AM, Gur I, Ertem U et al. Once daily ceftriaxone for meningococcemia and meningicoccal meningitis. Pediatr Infect Dis J . 1988; 7:711-3. [PubMed 3054778]

259. Bradley JS, Ching DK, Phillips SE. Outpatient therapy of serious pediatric infections with ceftriaxone. Pediatr Infect Dis J . 1988; 7:160-4. [PubMed 3357713]

260. Hook EW, Roddy RE, Handsfield HH. Ceftriaxone therapy for incubating and early syphilis. J Infect Dis . 1988; 158:881-4. [PubMed 3171231]

261. Dattwyler RJ, Halperin JJ, Volkman DJ et al. Treatment of late Lyme borreliosis—randomized comparison of ceftriaxone and penicillin. Lancet . 1988; 1:1191-4. [PubMed 2897008]

263. Valour F, Sénéchal A, Dupieux C et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist . 2014; 7:183-97. [PubMed 25045274]

264. Nassif X, Dupont B, Fleury J et al. Ceftriaxone in relapsing fever. Lancet . 1988; 2:394. [PubMed 2899795]

265. Fujita K, Murono K, Sakata H et al. [Ceftriaxone in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on intestinal bacterial flora.] (Japanese; with English abstract.) Jpn J Antibiot . 1988; 41:117-27.

266. Schwartz B, Al-Tobaiqi A, Al-Ruwais A et al. Comparative efficacy of ceftriaxone and rifampicin in eradicating pharyngeal carriage of group A Neisseria meningitidis . Lancet . 1988; 1:1239-42. [PubMed 2897515]

267. Islam A, Butler T, Nath SK et al. Randomized treatment of patients with typhoid fever by using ceftriaxone or chloramphenicol. J Infect Dis . 1988; 158:742-7. [PubMed 3171225]

268. Fink S, Karp W. Robertson A. Ceftriaxone effect on bilirubin-albumin binding. Pediatrics . 1987; 80:873-5. [PubMed 3684399]

269. Centers for Disease Control. Sexually transmitted diseases treatment guidelines 1989. MMWR Morb Mortal Wkly Rep . 1989; 38(Suppl 8S):1-43S. [PubMed 2491906]

270. Girgis NI, Farid Z, Bishay E. Ceftriaxone in bacterial meningitis. Lancet . 1989; 2:510.

271. Girgis NI, Abu EEA, Farid Z et al. Ceftriaxone compared with a combination of ampicillin and chloramphenicol in the treatment of bacterial meningitis in adults. Drugs Exp Clin Res . 1987; 13:497-500. [PubMed 3428132]

272. Girgis NI, Abu EEA, Farid Z et al. Intramuscular ceftriaxone versus ampicillin-chloramphenicol in childhood bacterial meningitis. Scand J Infect Dis . 1988; 20:613-7. [PubMed 3065929]

273. Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis . 1995; 20(Suppl 1):S47-65.

274. Le Saux N, Ronald AR. Role of ceftriaxone in sexually transmitted diseases. Rev Infect Dis . 1989; 11:299-309. [PubMed 2649963]

275. The United States pharmacopeia, 22nd rev, and The national formulary, 17th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1989(Suppl 1):2105-6.

276. Steere AC, Pachner AR, Malawista SE. Neurologic abnormalities in Lyme disease: successful treatment with high-dose intravenous penicillin. Ann Intern Med . 1983; 99:767-72. [PubMed 6316826]

277. . Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep . 2007; 56:332-6. [PubMed 17431378]

278. Reichenbach J, Lopatin U, Mahlaoui N et al. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis . 2009; 49:1703-10. [PubMed 19874205]

279. Luft BJ, Gorevic PD, Halperin JJ et al. A perspective on the treatment of Lyme borreliosis. Rev Infect Dis . 1989; 11(Suppl 6):S1518-25.

280. Dattwyler RJ, Halperin JJ, Volkman DJ et al. Treatment of late Lyme borreliosis—randomized comparison of ceftriaxone and penicillin. Lancet . 1988; 1:1191-4. [PubMed 2897008]

281. Eichenfield AH, Athreya BH. Lyme disease: of ticks and titers. J Pediatr . 1989; 114:328-33. [PubMed 2644410]

282. Neu HC. A perspective on therapy of Lyme infection. Ann NY Acad Sci . 1988; 539:314-6. [PubMed 3056200]

283. Luft BJ, Volkman DJ, Halperin JJ et al. New chemotherapeutic approaches in the treatment of Lyme borreliosis. Ann NY Acad Sci . 1988; 539:352-61. [PubMed 3056203]

284. Mursic VP, Wilske B, Schierz G. In vitro and in vivo susceptibility of Borrelia burgdorferi. Eur J Clin Microbiol . 1987; 6:424-6. [PubMed 3665899]

285. Johnson RC, Kodner C, Russell M. In vitro and in vivo susceptibility of the Lyme disease spirochete, Borrelia burgdorferi, to four antimicrobial agents. Antimicrob Agents Chemother . 1987; 31:164-7. [PubMedCentral][PubMed 3566246]

286. Dattwyler RJ, Halperin JJ, Pass H et al. Ceftriaxone as effective therapy in refractory Lyme disease. J Infect Dis . 1987; 155:1322-5. [PubMed 3572042]

287. Kohler J, Schneider H, Vogt A. High-dose intravenous penicillin G does not prevent further progression in early neurological manifestation of Lyme borreliosis. Infection . 1989; 17(Jul/Aug):216-7. [PubMed 2767763]

288. Johnson RC. Isolation techniques for spirochetes and their sensitivity to antibiotics in vitro and in vivo. Rev Infect Dis . 1989; 11(Suppl 6):S1505-10. [PubMed 2682963]

289. Berger BW, Johnson RC. Clinical and microbiological findings in 6 patients with erythema migrans of Lyme disease. J Am Acad Dermatol . 1989. In press.

290. Reviewers' comments on Lyme disease revisions (personal observations). 1989 Dec 4.

291. Rolfs R (Centers for Disease Control; Atlanta, GA). Personal communication; 1991 Sept 20.

292. American Academy of Pediatrics. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.

293. Marcuse EK. (American Academy of Pediatrics; Elk Grove Village, IL). Personal communication; 1991 Sept 25.

294. Harnoss BM, Hirner A, Dibbelt H et al. Perioperative antibiotic prophylaxis in bile-duct interventions: results of two prospective randomized studies. Chemotherapy . 1987; 33:297-301. [PubMed 3608630]

295. Hjortrup A, Moesgaard F, Jensen F et al. Antibiotic prophylaxis in high risk biliary surgery: one dose of ceftriaxone compared with two doses of cefuroxime. Eur J Surg . 1991; 157:403-5. [PubMed 1681918]

296. El-Mufti M, Rakas FS, Glessa A et al. Ceftriaxone versus clavulanate-potentiated amoxycillin for prophylaxis against postoperative sepsis in biliary surgery: a prospective randomized study in 200 patients. Curr Med Res Opin . 1989; 11:354-9. [PubMed 2707048]

297. Kujath P. Brief report: antibiotic prophylaxis in biliary tract surgery: ciprofloxacin versus ceftriaxone. Am J Med . 1989; 87(Suppl 5A):S255-7. [PubMed 2511759]

298. Skinner JM. Letter regarding revised labeling for the use of Rocephin® (ceftriaxone sodium) as prophylaxis against infections in patients undergoing biliary tract surgery. Nutley, NJ: Roche Laboratories; 1992 Jun.

299. Centers for Disease Control and Prevention. Diagnosis and management of foodborne illness. A primer for physicians. MMWR Recomm Rep . 2001; 50( RR-2):1-69. [Fulltext MMWR]

300. Meijer WS, Schmitz PIM, Jeekel J. Meta-analysis of randomized, controlled clinical trials of antibiotic prophylaxis in biliary tract surgery. Br J Surg . 1990; 77:283-90. [PubMed 2138925]

301. Classen DC, Evans RS, Pestotnik SL et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med . 1992; 326:281-6. [PubMed 1728731]

302. McDonald LC, Gerding DN, Johnson S et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis . 2018; 66:987-994. [PubMed 29562266]

303. Fekety R for the American College of Gastroenterology Practice parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile - associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. [PubMed 9149180]

304. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970]

305. Bauer MP, Kuijper EJ, van Dissel JT et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect . 2009; 15:1067-79. [PubMed 19929973]

308. Zinberg J, Chernaik R, Coman E et al. Reversible symptomatic biliary obstruction associated with ceftriaxone pseudolithiasis. J Gastroenterology . 1991; 86:1251-4.

309. Lopez AJ, O'Keefe P, Morrissey M. Ceftriaxone-induced cholelithiasis. Ann Intern Med . 1991; 115:712-4. [PubMed 1929040]

310. Barnett ED, Teele DW, Klein JO et al. Comparison of ceftriaxone and trimethoprim- sulfamethoxazole for acute otitis media. Pediatrics . 1997; 99:23-8. [PubMed 8989332]

311. Green SM, Rothrock SG. Single-dose intramuscular ceftriaxone for acute otitis media in children. Pediatrics . 1993; 91:23-30. [PubMed 8416502]

312. Varsano I, Frydman M, Amir J et al. Single intramuscular dose of ceftriaxone as compared to 7-day amoxicillin therapy for acute otitis media in children: a double-blind clinical trial. Chemotherapy . 1988; 34(Suppl 1):39-46. [PubMed 3246170]

313. Fraschini F, Braga PC, Falchi M et al. Ceftriaxone therapy in otolaryngological and pulmonary infections. Chemotherapy . 1986; 32:200-4. [PubMed 3709268]

314. Patel R, Grogg KL, Edwards WD et al. Death from inappropriate therapy for Lyme disease. Clin Infect Dis . 2000 Oct; 31:1107-9.

315. Centers for Disease Control and Prevention. Ceftriaxone-associated biliary complications of treatment of suspected disseminated Lyme disease—New Jersey, 1990-1992. MMWR Morb Mortal Wkly Rep . 1993; 42:39-42. [PubMed 8419791]

316. Shiffman ML, Keith FB, Moore EW. Pathogenesis of ceftriaxone-associated biliary sludge: in vitro studies of calcium-ceftriaxone binding and solubility. Gastroenterology . 1990; 99:1772-8. [PubMed 2227290]

317. Heim-Duthoy KL, Caperton EM, Pollock R et al. Apparent biliary pseudolithiasis during ceftriaxone therapy. Antimicrob Agents Chemother . 1990; 34:1146-9. [PubMedCentral][PubMed 2203305]

318. Centers for Disease Control and Prevention. Sentinel surveillance for antimicrobial resistance in Neisseria gonorrhoeae —United States, 1988-1991. MMWR Morb Mortal Wkly Rep . 1993; 42(SS-3):29-39.

319. Spach DH, Liles WC, Campbell GL et al. Tick-borne diseases in the United States. N Engl J Med . 1993; 329:936-47. [PubMed 8361509]

320. Luft BJ, Gardner P, Lightfoot RW Jr. Appropriateness of parenteral antibiotic treatment for patients with presumed Lyme disease. Ann Intern Med . 1993; 119:518. [PubMed 8357119]

321. Lightfoot RW, Luft BJ, Rahn DW et al. Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis. Ann Intern Med . 1993; 119:503-9. [PubMed 8357117]

322. Bakken LL, Case KL, Callister SM et al. Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology. JAMA . 1992; 268:891-5. [PubMed 1640618]

323. Anon. Prevalence of penicillin-resistant Streptococcus pneumoniae —Connecticut, 1992-1993. MMWR Morb Mortal Wkly Rep . 1994; 43:216,217,223. [PubMed 8127327]

324. Leggiadro RJ. Penicillin- and cephalosporin-resistant Streptococcus pneumoniae : an emerging threat. Pediatrics . 1994;93:500-3. [PubMed 8115213]

325. Saxon A, Beall GN, Rohr AS et al. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med . 1987; 107:204-15. [PubMed 3300459]

326. Centers for Disease Control and Prevention. Decreased susceptibility of Neisseria gonorrhoeae to fluoroquinolones—Ohio and Hawaii, 1992-1994. MMWR Morb Mortal Wkly Rep . 1994; 43:325-7. [PubMed 8164636]

328. Jaber MR, Olafsson S, Fung WL et al. Clinical review of the management of fulminant Clostridium difficile infection. Am J Gastroenterol . 2008; 103:3195-203; quiz 3204. [PubMed 18853982]

329. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis . 2006; 43:1089-134. [PubMed 17029130]

330. Centers for Disease Control and Prevention. Drug-resistant Streptococcus pneumoniae —Kentucky and Tennessee, 1993. MMWR Morb Mortal Wkly Rep . 1994; 43:23-7. [PubMed 8277937]

331. Friedland IR, Shelton S, Paris M et al. Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J . 1993; 12:196-200. [PubMed 8451095]

332. Chesney PJ. The escalating problem of antimicrobial resistance in Streptococcus pneumoniae . Am J Dis Child . 1992; 146:912-6. [PubMed 1636656]

333. Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbiol Rev . 1990; 3:171-96. [PubMedCentral][PubMed 2187594]

334. John CC. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis . 1994; 18:188-93. [PubMed 8161625]

335. Baxter Healthcare Corporation. Descriptive information on premixed products. Deerfield, IL; 1994 Feb 21.

336. Hook EW, Jones RB, Martin DH et al. Comparison of ciprofloxacin and ceftriaxone as single-dose therapy for uncomplicated gonorrhea in women. Antimicrob Agents Chemother . 1993; 37:1670-3. [PubMedCentral][PubMed 8215281]

337. Schwarcz SK, Zenilman JM, Schnell D et al. National surveillance of antimicrobial resistance in Neisseria gonorrhoeae . JAMA . 1990; 264:1413-7. [PubMed 2144026]

338. Lascari AD, Amyot K. Fatal hemolysis caused by ceftriaxone. J Pediatr . 1995; 126:816-7. [PubMed 7752013]

339. Bernini JC, Mustafa MM, Sutor LJ et al. Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia. J Pediatr . 1995; 126:813-5. [PubMed 7752012]

340. Agger WA, Callister SM, Jobe DA. In vitro susceptibility of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. Antimicrob Agents Chemother . 1992; 36:1788-90. [PubMedCentral][PubMed 1416868]

341. Johnson RC, Kodner CB, Jurkovich PJ et al. Comparative in vitro and in vivo susceptibilities of the Lyme disease spirochete Borrelia burgdorferi to cefuroxime and other antimicrobial agents. Antimicrob Agents Chemother . 1990; 34:2133-6. [PubMedCentral][PubMed 2073103]

342. Halperin JJ, Shapiro ED, Logigian E et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology . 2007; 69:91-102. [PubMed 17522387]

343. Klass PE, Klein JO. Therapy of bacterial sepsis, meningitis and otitis media in infants and children: 1992 poll of directors of programs in pediatric infectious diseases. Pediatr Infect Dis J . 1992; 11:702-5. [PubMed 1448307]

344. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep . 2015; 64(RR-03):1-137. [PubMed 26042815]

345. . Drugs for sexually transmitted infections. Med Lett Drugs Ther . 2017; 59:105-112. [PubMed 28686575]

346. Tomasz A. The pneumococcus at the gates. N Engl J Med . 1995; 333:514-5. [PubMed 7623886]

347. Hofmann J, Cetron MS, Farley MM et al. The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. N Engl J Med . 1995; 333:481-6. [PubMed 7623880]

348. Barry AL, Brown SD, Novick WJ. In vitro activities of cefotaxime, ceftriaxone, ceftazidime, cefpirome, and penicillin against Streptococcus pneumoniae isolates. Antimicrob Agents Chemother . 1995; 39:2193-6. [PubMedCentral][PubMed 8619565]

349. Sloas NM, Barrett FF, Chesney PJ et al. Cephalosporin treatment failures in penicillin- and cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J . 1992; 11:662-6. [PubMed 1523079]

350. World Health Organization. WHO guidelines for treatment of Treponema pallidum (syphilis). Geneva, Switzerland; WHO; 2016. Available at WHO website. [Web]

352. Centers for Disease Control and Prevention. Outbreak of multidrug-resistant Salmonella Newport—United States, January-April 2002. MMWR Morb Mortal Wkly Rep . 2002; 51:545-7. [PubMed 12118534]

353. Steere AC, Green J, Schoen RT et al. Successful parenteral penicillin therapy of established Lyme arthritis. N Engl J Med . 1985; 312:869-74. [PubMed 3883177]

354. Rolain JM, Brouqui P, Koehler JE et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother . 2004; 48:1921-33. [PubMed 15155180]

355. Martin C, Ragni J, Lokiec F et al. Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery. Antimicrob Agents Chemother . 1992; 36:2804-7. [PubMedCentral][PubMed 1482149]

356. Rahn DW, Malawista SE. Lyme disease: recommendations for diagnosis and treatment. Ann Intern Med . 1991; 114:472-81. [PubMed 1994795]

357. Nocton JJ, Steere AC. Lyme disease. Adv Intern Med . 1995; 40:69-117. [PubMed 7747659]

358. Spach DH, Liles WC, Campbell GL et al. Tick-borne diseases in the United States. N Engl J Med . 1993; 329:936-47. [PubMed 8361509]

359. Jantausch BA. Lyme disease, Rocky Mountain spotted fever, ehrlichiosis: emerging and established challenges for the clinician. Ann Allergy . 1994; 73:4-11. [PubMed 8030801]

360. . Antimicrobial prophylaxis for surgery. Med Lett Drugs Ther . 2016; 58:63-8. [PubMed 27192618]

361. Sigal LH. Early disseminated Lyme disease: cardiac manifestations. Am J Med . 1995; 98(4A):25-28S.

362. Steere AC. Musculoskeletal manifestations of Lyme disease. Am J Med . 1995; 98(4A):44-48S.

363. Sigal LH. Management of Lyme disease refractory to antibiotic therapy. Rheum Dis Clin North Am . 1995; 21:217-30. [PubMed 7732170]

364. Dattwyler RJ, Luft BJ, Kunkel MJ et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated lyme disease. N Engl J Med . 1997; 337:289-94. [PubMed 9233865]

365. Shapiro ED. Lyme disease in children. Am J Med . 1995; 98(4A):69-73S.

366. Pachner AR. Early disseminated Lyme disease: Lyme meningitis. Am J Med . 1995; 98(4A):30-37S.

367. Sigal LH. Persisting symptoms of Lyme disease—possible explanations and implications for treatment. J Rheumatol . 1994; 21:593-5. [PubMed 8035381]

368. Rees DHE, Axford JS. Lyme arthritis. Ann Rheum Dis . 1994; 53:553-6. [PubMedCentral][PubMed 7979590]

369. Ettestad PJ, Campbell GL, Welbel SF et al. Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis . 1995; 171:356-61. [PubMed 7844372]

370. Gasser RN, Dusleag J, Reisinger EC et al. Treatment of long-standing Lyme disease with ceftriaxone. Lancet . 1994; 343:1227. [PubMed 7909891]

371. Sigal LH. Lyme disease: primum non nocere. J Infect Dis . 1995; 171:423-4. [PubMed 7844380]

372. Billstein SA, Sudol TE. Ceftriaxone for pediatric patients with Lyme disease. J Infect Dis . 1994; 169:937-8. [PubMed 8204175]

373. Spielman A, Shih CM. Ceftriaxone for pediatric patients with Lyme disease. J Infect Dis . 1994; 169:938. [PubMed 8133116]

374. Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm . 2013; 70:195-283. [PubMed 23327981]

375. Schwartz B. Chemoprophylaxis for bacterial infections: principles of and application to meningococcal infections. Rev Infect Dis . 1991; 13(Suppl 2):S170-3. [PubMedCentral][PubMed 2017647]

376. Cohn AC, MacNeil JR, Clark TA et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2013; 62(RR-2):1-28. [PubMed 23515099]

378. Martin C, Viviand X, Alaya M et al. Penetration of ceftriaxone (1 or 2 grams intravenously) into mediastinal and cardiac tissues in humans. Antimicrob Agents Chemother . 1996; 40:812-5. [PubMedCentral][PubMed 8851621]

379. Hayward CJ, Nafziger AN, Kohlhepp SJ et al. Investigation of bioequivalence and tolerability of intramuscular ceftriaxone injections by using 1% lidocaine, buffered lidocaine, and sterile water diluents. Antimicrob Agents Chemother . 1996; 40:485-7. [PubMedCentral][PubMed 8834905]

380. Hamded KA. Successful treatment of primary Actinomyces viscosus endocarditis with third-generation cephalosporins. Clin Infect Dis . 1998; 26:211-2. [PubMed 9455552]

381. Skoutelis A, Petrochilos J, Bassaris H. Successful treatment of thoracic actinomycosis with ceftriaxone. Clin Infect Dis . 1994; 19:161-2. [PubMed 7948522]

382. Smego RA, Foglia G. Actinomycosis. Clin Infect Dis . 1998; 26:1255-63. [PubMed 9636842]

383. Singer R. Diagnosis and treatment of Whipple's disease. Drugs . 1998; 55:699- 704. [PubMed 9585865]

384. Peters FP, Wouters RS, de Bruine AP et al. Cerebral relapse of sarcoidlike Whipple's disease. Clin Infect Dis . 1997; 24:1252-5. [PubMed 9195094]

385. Schnider PJ, Reisinger EC, Gerschlager W et al. Long-term follow-up in cerebral Whipple's disease. Eur J Gastroenterol Hepatol . 1996; 8:899-903. [PubMed 8889458]

386. Adler CH, Galetta SL. Oculo-facial-skeletal myorhythmia in Whipple disease: treatment with ceftriaxone. Ann Intern Med . 1990; 112:467-9. [PubMed 1689977]

387. Charnas R, Luthi AR, Ruch W et al. Once daily ceftriaxone plus amikacin vs. three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer. Pediatr Infect Dis J . 1997; 16:346-53. [PubMed 9109134]

388. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann Intern Med . 1993; 119:584-93. [PubMed 8363169]

389. Cordonnier C, Herbrecht R, Pico JL et al et al. cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. Clin Infect Dis . 1997; 24:41-51. [PubMed 8994754]

390. Prince SE, Dominger KA, Cunha BA et al. Klebsiella pneumoniae pneumonia. Heart Lung . 1997; 26:413-7. [PubMed 9315470]

391. Meyer DJ, Gerding DN. Favorable prognosis of patients with prosthetic valve endocarditis caused by gram-negative bacilli of the HACEK group. Am J Med . 1988; 85:104-7. [PubMed 3291611]

392. Ramphal R, Gucalp R, Rotstein C et al. Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am J Med . 1996; 100(Suppl 6A):83S-89S. [PubMed 8678102]

393. Viscoli C. The evolution of the empirical management of fever and neutropenia in cancer patients. J Antimicrob Chemother . 1998; 41(Suppl D):65-80. [PubMed 9688453]

394. Rolston KV. Expanding the options for risk-based therapy in febrile neutropenia. Diagn Microbiol Infect Dis . 1998; 31:411-6. [PubMed 9635917]

395. Link H, Maschmeyer G, Meyer P et al. Interventional antimicrobial therapy in febrile neutropenic patients. Ann Hematol . 1994; 69:231-43. [PubMed 7948312]

396. Spach DH, Kanter AS, Dougherty MJ et al. Bartonella ( Rochalimaea ) quintana bacteremia in inner-city patients with chronic alcoholism. N Engl J Med . 1995; 332:424-8. [PubMed 7529895]

397. Walker CK, Kahn JG, Washington AE et al. Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis . 1993; 168:969-78. [PubMed 8376843]

398. Cunha BA. Treatment of pelvic inflammatory disease. Clin Pharm . 1990; 9:275-85. [PubMed 2184973]

399. Hemsell DL, Little BB, Faro S et al. Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease. Clin Infect Dis . 1994; 19:720-7. [PubMed 7803638]

400. Brouqui P, Houpikian P, Dupont HT et al. Survey of seroprevalence of Bartonella quintana in homeless people. Clin Infect Dis . 1996; 23:756-9. [PubMed 8909840]

401. Eidlitz-Marcus T, Cohen YH, Nussinovitch M et al. Comparative efficacy of two- and five-day courses of ceftriaxone for treatment of severe shigellosis in children. J Pediatr . 1993; 123:822-4. [PubMed 8229499]

402. Varsano I, Eidlitz-Marcus T, Nussinovitch M et al. Comparative efficacy of ceftriaxone and ampicillin for treatment of severe shigellosis in children. J Pediatr . 1991; 188:627-32.

403. Nataro JP. Treatment of bacterial enteritis. Pediatr Infect Dis J . 1998; 17:420-2. [PubMed 9613658]

404. Zenilman JM. Typhoid fever. JAMA . 1997; 278:847-50. [PubMed 9293994]

405. Herikstad H, Hayes PS, Hogan J et al. Ceftriaxone-resistant Salmonella in the United States. Pediatr Infect Dis J . 1997; 16:904-5. [PubMed 9306487]

406. Smith MD, Duong NM, Hoa NTT et al. Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever. Antimicrob Agents Chemother . 1994; 38:1716-20. [PubMedCentral][PubMed 7986000]

407. Islam A, Butler T, Kabir I et al. Treatment of typhoid fever with ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized clinical trial. Antimicrob Agents Chemother . 1993; 37:1572-5. [PubMedCentral][PubMed 8215265]

408. Bhutta ZA, Khan IA, Molla AM. Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone. Pediatr Infect Dis J . 1994; 13:990-4. [PubMed 7845753]

409. Girgis NI, Sultan Y, Hammad O et al. Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children. Pediatr Infect Dis J . 1995; 14:603-5. [PubMed 7567290]

410. Soe GB, Overturf GD. Treatment of typhoid fever and other systemic salmonelloses with cefotaxime, ceftriaxone, cefoperazone, and other newer cephalosporins. Rev Infect Dis . 1987; 9:719-36. [PubMed 3125577]

411. Mermin JH, Townes JM, Gerber M et al. Typhoid fever in the United States, 1985- 1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med . 1998; 158:633-8. [PubMed 9521228]

413. Abo Rahmy E. Perioperative antibiotic prophylaxis in abdominal surgery for hernia repair: retrospective study of 1,524 consecutive patients. J Chemother . 1998; 10:248-53. [PubMed 9669652]

414. Kaye D. Treatment of infective endocarditis. Ann Intern Med . 1996; 124:606- 8. [PubMed 8597326]

415. Francioli PB. Ceftriaxone and outpatient treatment of infective endocarditis. Infect Dis Clin N Am . 1993; 7:97-115.

416. Tunkel AR, Hasbun R, Bhimraj A et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis . 2017; [PubMed 28203777]

417. Francioli P, Etienne J, Hoigne R et al. Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone sodium for 4 weeks. Efficacy and outpatient treatment feasibility. JAMA . 1992; 267:264-7. [PubMed 1727524]

418. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis . 2004; 39:1267-84. [PubMed 15494903]

419. Feigin RD, McCracken GH, Klein JO. Diagnosis and management of meningitis. Pediatr Infect Dis J . 1992; 11:785-814. [PubMed 1448332]

420. Lossos IS, Lossos A. Hazards of rapid administration of ceftriaxone. Ann Pharmacother . 1994; 28:807-8. [PubMed 7919578]

421. Russo TA, Cook S, Gorbach S. Intramuscular ceftriaxone in home parenteral therapy. Antimicrob Agents Chemother . 1988; 32:1439-40. [PubMedCentral][PubMed 3196006]

422. Williams DN, Rehm SJ, Tice AD et al. Practice guidelines for community-based parenteral anti-infective therapy. Clin Infect Dis . 1997; 25:787-801. [PubMed 9356790]

423. Leibovitz E, Tabachnik E, Fliedel O et al. Once-daily intramuscular ceftriaxone in the outpatient treatment of severe community-acquired pneumonia in children. Clin Pediatr . 1990; 29:634-9.

424. Bradley JS. Once-daily ceftriaxone in the outpatient treatment of paediatric infections. Chemotherapy . 1991; 37(Suppl 3):3-6. [PubMed 1884651]

425. Tice AD. Once-daily ceftriaxone outpatient therapy in adults with infections. Chemotherapy . 1991; 37(Suppl 3):7-10. [PubMed 1909231]

426. Wiselka MJ, Nicholson KG. Outpatient parenteral antimicrobial therapy: experience in a large teaching hospital. J Infect . 1997; 35:73-6. [PubMed 9279728]

427. Chamberlain JM, Boenning DA, Waisman Y et al. Single-dose ceftriaxone versus 10 days of cefaclor for otitis media. Clin Pediatr . 1994; Nov:642-6.

428. Kozyrskyj AL, Hildes-Ripstein GE, Longstaffe SEA et al. Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis. JAMA . 1998; 279:1736-42. [PubMed 9624028]

429. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J . 1997; 16:680-95. [PubMed 9239773]

430. Bauchner H, Adams W, Barnett E et al. Therapy for acute otitis media: preference of parents for oral or parenteral antibiotics. Arch Pediatr Adolesc Med . 1996; 150:396-9. [PubMed 8634735]

431. Goldfarb J, Medendorp S. New therapies for otitis media. Clin Pediatr . 1994; Nov:647-8.

432. Kishiyam JL, Adelman DC. The cross-reactivity and immunology of β-lactam antibiotics. Drug Safety . 1994; 10:318-27. [PubMed 8018304]

433. Thompson JW, Jacobs RF. Adverse effects of newer cephalosporins: an update. Drug Safety . 1993; 9:132-42. [PubMed 8397890]

434. Kleiman MB, Weinberg GA, Reynolds JK et al. Meningitis with beta-lactam-resistant Streptococcus pneumoniae : the need for early repeat lumbar puncture. Pediatr Infect Dis J . 1993; 12:782-4. [PubMed 8414810]

435. Adu A, Armour CL. Drug utilisation review (DUR) of the third generation cephalosporins: focus on ceftriaxone, ceftazidime and cefotaxime. Drugs . 1995; 50:423- 39. [PubMed 8521766]

436. Giamarellou H. Empiric therapy for infections in the febrile, neutropenic, compromised host. Med Clin N Am . 1995; 79:559-77. [PubMed 7752729]

437. Girmenia C, Moleti ML, Cartoni C et al. Management of infective complications in patients with advanced hematologic malignancies in home care. Leukemia . 1997; 11:1807-12. [PubMed 9369410]

438. Berbari EF, Cockerill FR, Steckelberg JM. Infective endocarditis due to unusual or fastidious microorganisms. Mayo Clin Proc . 1997; 72:532-42. [PubMed 9179137]

439. Das M, Badley DM, Cockerill FR et al. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med . 1997; 48:25-33. [PubMed 9046942]

440. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed February 26, 2018. Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

442. Reed JB, Scales DK, Wong MT et al. Bartonella henselae neuroretinitis in cat scratch disease: diagnosis, management, and sequelae. Ophthalmology . 1998; 105:459-66. [PubMed 9499776]

443. Tan JS. Human zoonotic infections transmitted by dogs and cats. Arch Intern Med . 1997; 157:1933-43. [PubMed 9308505]

444. Bass JW, Freitas BC, Freitas AD et al. Prospective randomized double blind placebo- controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J . 1998; 17:447-52. [PubMed 9655532]

445. Smith DL. Cat-scratch disease and related clinical syndromes. Am Fam Physician . 1997; 55:1783-9. [PubMed 9105205]

446. Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med . 1993; 329:1328-34. [PubMed 8413414]

447. DiCarlo RP, Martin DH. The clinical diagnosis of genital ulcer disease in men. Clin Infect Dis . 1997; 25:292-9. [PubMed 9332527]

448. Zervos M, Nelson M, and the Cefepime Study Group. Cefepime versus ceftriaxone for empiric treatment of hospitalized patients with community-acquired pneumonia. Antimicrob Agents Chemother . 1998; 42:729-33. [PubMedCentral][PubMed 9559773]

449. Lippert H, Gastinger J. Antimicrobial prophylaxis in laparoscopic and conventional cholecystectomy. Chemotherapy . 1998; 44:355-63. [PubMed 9732152]

450. Baddour LM, Wilson WR, Bayer AS et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation . 2015; 132:1435-86. [PubMed 26373316]

451. Wilson W, Taubert KA, Gewitz M et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation . 2007; 116:1736-54. [PubMed 17446442]

452. Baltimore RS, Gewitz M, Baddour LM et al. Infective Endocarditis in Childhood: 2015 Update: A Scientific Statement From the American Heart Association. Circulation . 2015; 132:1487-515. [PubMed 26373317]

453. Karthaus M, Wolf HH, Kampfe D et al. Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. Chemotherapy . 1998; 44:343-54. [PubMed 9732151]

454. Bartolozzi S, Clerico A, Properzi E et al. Ceftriaxone as a single agent in empirical therapy of unexplained fever in granulocytopenic children with solid tumors. J Chemother . 1997; 9:227-31. [PubMed 9210007]

455. Wing DA, Hendershott CM, Debuque l et al. A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy. Obstet Gynecol . 1998; 92:249- 53. [PubMed 9699761]

456. Laurichesse H, Robin F, Gerbaud L et al. Empirical therapy for nonhospitalized patients with community-acquired pneumonia. Eur Respir J . 1998; 11:73-8. [PubMed 9543273]

457. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Disease Society of America. Clin Infect Dis . 2011; 52:e56-93.

458. Varsano I, Volovitz B, Horev Z et al. Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children. Eur J Pediatr . 1997; 156:858-63. [PubMed 9392401]

459. Duff P. Antibiotic selection in obstetric patients. Infect Dis Clin North Am . 1997; 11:1-12. [PubMed 9067781]

460. Arredondo JL, Diaz V, Gaitan H et al. Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients. Clin Infect Dis . 1997; 24:170-8. [PubMed 9114143]

461. Hawkey PM, Smith SD, Haynes J et al. In vitro susceptibility of Capnocytophaga species to antimicrobial agents. Antimicrob Agents Chemother . 1987; 31:331-2. [PubMedCentral][PubMed 3566254]

462. Rummen JL, Gordts B, Van Landuyt HW. In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents. Antimicrob Agents Chemother . 1986; 30:739-42. [PubMedCentral][PubMed 3800350]

463. Pers C, Gahrn-Hansen B, Frederiksen W. Capnocytophaga canimorsus septicemia in Denmark, 1982-1995: review of 39 cases. Clin Infect Dis . 1996; 23:71-5. [PubMed 8816132]

464. Spach DH, Koehler JE. Bartonella -associated infections. Infect Dis Clin N Am . 1998; 12:137-55.

465. Bass JW, Vincent JM, Person DA. The expanding spectrum of Bartonella infections: I. Bartonellosis and trench fever. Pediatr Infect Dis J . 1997; 16:2-10. [PubMed 9002093]

466. Fass RJ, Barnishan J, Solomon MC et al. In vitro activities of quinolones, β-lactams, tobramycin, and trimethoprim-sulfamethoxazole against nonfermentative gram-negative bacilli. Antimicrob Agents Chemother . 1996; 40:1412-8. [PubMedCentral][PubMed 8726011]

468. Townsend GC, Scheld WM. Infections of the central nervous system. Adv Intern Med . 1998; 43:403-47. [PubMed 9506189]

469. Buchingham SC, Brown SP, San Joaquin VH. Breakthrough bacteremia and meningitis during treatment with cephalosporins parenterally for pneumococcal pneumonia. J Pediatr . 1998; 132:174-6. [PubMed 9470026]

470. Pacheco TR, Cooper CK, Hardy DJ et al. Failure of cefotaxime treatment in an adult with Streptococcus pneumoniae meningitis. Am J Med . 1997; 102:303-5. [PubMed 9217602]

471. Wubbel L, McCracken GH. Management of bacterial meningitis: 1998. Pediatr Rev . 1998; 19:78-84. [PubMed 9509854]

472. McIntyre PB, Berkey CS, King SM et al. Dexamethasone as adjunctive therapy in bacterial meningitis: a meta-analysis of randomized clinical trials since 1988. JAMA . 1997; 278:925-31. [PubMed 9302246]

473. Cabellos C, Viladrich PF, Verdaguer R et al. A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature. Clin Infect Dis . 1995; 20:1164-8. [PubMed 7619994]

474. Chesney PJ, Halsey NA, Marcy SM. Treatment of bacterial meningitis. N Engl J Med . 1997; 337:793-4. [PubMed 9289652]

475. Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med . 1997; 336:708-16. [PubMed 9041103]

476. Bhattacharya S. Management of meningitis caused by penicillin-resistant Streptococcus pneumoniae . Antimicrob Agents Chemother . 1996; 40:827-8. [PubMedCentral][PubMed 8851626]

478. Mathisen GE, Johnson JP. Brain abscess. Clin Infect Dis . 1997; 25:763-81. [PubMed 9356788]

479. Lorber B. Listeriosis. Clin Infect Dis . 1997; 24:1-11. [PubMed 8994747]

480. Reviewers' comments (personal observations).

481. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet . 1998; 352:557-65. [PubMed 9716075]

482. Sobraques M, Maurin M, Birtles RJ et al. In vitro susceptibilities of four Bartonella bacilliformis strains to 30 antibiotic compounds. Antimicrob Agents Chemother . 1999; 43:2090-2. [PubMedCentral][PubMed 10428946]

483. Aracil B, Gomez-Garces JL, Alos JI. A study of susceptibility of 100 clinical isolates belonging to the Streptococcus milleri group to 16 cephalosporins. J Antimicrob Chemother . 1999; 43:399-402. [PubMed 10223596]

484. Silverstein M, Bacher R, Harper MB. Clinical implications of penicillin and ceftriaxone resistance among children with pneumococcal bacteremia. Pediatr Infect Dis J . 1999; 18:35-41. [PubMed 9951978]

485. Nicolau DP, Tessler PR, Quintiliani R et al. Synergistic activity of trovafloxacin and ceftriaxone or vancomycin against Streptococcus pneumoniae with various penicillin susceptibilities. Antimicrob Agents Chemother . 1998; 42:991-2. [PubMedCentral][PubMed 9559832]

488. Gudnason T, Gudbrandsson F, Barsanti F et al. Penetration of ceftriaxone into the middle ear fluid of children. Pediatr Infect Dis J . 1998; 17:258-60. [PubMed 9535262]

489. Scaglione F, De Martini G, Peretto L et al. Pharmacokinetic study of cefodizime and ceftriaxone in sera and bones of patients undergoing hip arthroplasty. Antimicrob Agents Chemother . 1997; 41:2292-4. [PubMedCentral][PubMed 9333066]

491. Sexton DJ, Tenebaum MJ, Wilson WR et al. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Clin Infect Dis . 1998; 27:1470-4. [PubMed 9868662]

492. Logigian EL, Kaplan RF, Steere AC. Successful treatment of lyme encephalopathy with intravenous ceftriaxone. J Infect Dis . 1999; 180:377-83. [PubMed 10395852]

493. File TM, Segreti J, Dunbar L et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother . 1997; 41:1965-72. [PubMedCentral][PubMed 9303395]

495. Klempner MS, Hu LT, Evans J et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med . 2001; 345:85-92. [PubMed 11450676]

497. Steere AC. Lyme disease. N Engl J Med . 2001; 345:115-25. [PubMed 11450660]

498. Thompson C, Spielman A, Krause P. Coinfecting deer-associated zoonoses: Lyme disease, babebiosis, and ehrlichiosis. Clin Infect Dis . 2000; 33:676-85.

500. Elia S, Gentile M, Guggino G et al. Preoperative antimicrobial prophylaxis with a long-acting cephalosporin for thoracic surgery in 192 non small cell lung cancer patients. J Chemother . 1998; 10:58-63. [PubMed 9531076]

505. Guerrero MLF, Ramos JM, Nunez A et al. Focal infections due to non- typhi Salmonella in patients with AIDS: report of 10 cases and review. Clin Infect Dis . 1997; 25:690-7. [PubMed 9314463]

506. Tunkel AR, Glaser CA, Bloch KC et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis . 2008; 47:303-27. [PubMed 18582201]

507. Food and Drug Administration. Rocephin (ceftriaxone sodium) for injection [July 05, 2007]. MedWatch alert. Rockville, MD; July 2007. From FDA website. [Web]

509. Scholz M, Luftenegger W, Harmuth H et al. Single-dose antibiotic prophylaxis in transurethral resection of the prostate: a prospective randomized trial. Br J Urol . 1998; 81:827-9. [PubMed 9666765]

510. Food and Drug Administration. Rocephin (ceftriaxone sodium) for injection [September 11, 2007]. MedWatch alert. Rockville, MD; September 2007. From FDA website. [Web]

511. Food and Drug Administration. Ceftriaxone (marketed as Rocephin) Information for Healthcare Professionals. Rockville, MD; September 2007. From FDA website. [Web]

512. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis . 2007; 44 Suppl 2:S27-72. [PubMed 17278083]

513. Bradley JS, Byington CL, Shah SS et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis . 2011; 53:e25-76. Updates may be available at IDSA website at www.idsociety.org. [PubMed 21880587]

520. Bradley JS, Wassel RT, Lee L et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics . 2009; 123:e609-13. [PubMed 19289450]

526. van Gelderen de Komaid AA, Durán EL. Antimicrobial susceptibilities of strains of Nocardia brasiliensis isolated from soil of Tucumán. Mycopathologia . 1998; 141:115-21. [PubMed 9755502]

527. Khan Z, Al-Sayer H, Chugh TD et al. Antimicrobial susceptibility profile of soil isolates of Nocardia asteroides from Kuwait. Clin Microbiol Infect . 2000; 6:94-8. [PubMed 11168079]

529. Food and Drug Administration. Information for healthcare professionals. Ceftriaxone (marketed as Rocephin and generics). FDA update 04/21/2009. From FDA website. [Web]

535. Gehanno P, Nguyen L, Barry B et al. Eradication by ceftriaxone of Streptococcus pneumoniae isolates with increased resistance to penicillin in cases of acute otitis media. Antimicrob Agents Chemother . 1999; 43:16-20. [PubMedCentral][PubMed 9869558]

543. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis . 2014; 59:147-59. Updates may be available at IDSA website at www.idsociety.org. [PubMed 24947530]

544. Lipsky BA, Berendt AR, Cornia PB et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis . 2012; 54:e132-73. Updates may be available at IDSA website at www.idsociety.org. [PubMed 22619242]

590. Berbari EF, Kanj SS, Kowalski TJ et al. 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis . 2015; 61:e26-46. [PubMed 26229122]

591. Osmon DR, Berbari EF, Berendt AR et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis . 2013; 56:e1-e25. [PubMed 23223583]

613. Leibovitz E, Piglansky L, Raiz S et al. Bacteriologic efficacy of a three-day intramuscular ceftriaxone regimen in nonresponsive acute otitis media. Pediatr Infect Dis J . 1998; 17:1126-31. [PubMed 9877360]

614. Cohen R, Navel M, Grunberg J et al. One dose ceftriaxone vs ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora. Pediatr Infect Dis J . 1999; 18:403-9. [PubMed 10353511]

626. Moallen HJ, Garratty G, Wakeham M et al. Ceftriaxone-related fatal hemolysis in an adolescent with perinatally acquired human immunodeficiency virus infection. J Pediatr . 1998; 133:279-81. [PubMed 9709722]

665. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.

683. Lieberthal AS, Carroll AE, Chonmaitree T et al. The diagnosis and management of acute otitis media. Pediatrics . 2013; 131:e964-99. [PubMed 23439909]

688. Clark TR, Burns S. Elevated international normalized ratio values associated with concomitant use of warfarin and ceftriaxone. Am J Health Syst Pharm . 2011; 68:1603-5. [PubMed 21856805]

689. Saum LM, Balmat RP. Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections. J Pharm Pract . 2016; 29:121-4. [PubMed 25092605]

690. Panaphut T, Domrongkitchaiporn S, Vibhagool A et al. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis. Clin Infect Dis . 2003; 36:1507-13. [PubMed 12802748]

691. Farr RW. Leptospirosis. Clin Infect Dis . 1995; 21:1-6; quiz 7-8. [PubMed 7578715]

693. Suputtamongkol Y, Niwattayakul K, Suttinont C et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis . 2004; 39:1417-24. [PubMed 15546074]

694. Katz AR, Ansdell VE, Effler PV et al. Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998. Clin Infect Dis . 2001; 33:1834-41. [PubMed 11692294]

695. Griffith ME, Hospenthal DR, Murray CK. Antimicrobial therapy of leptospirosis. Curr Opin Infect Dis . 2006; 19:533-7. [PubMed 17075327]

696. Ressner RA, Griffith ME, Beckius ML et al. Antimicrobial susceptibilities of geographically diverse clinical human isolates of Leptospira. Antimicrob Agents Chemother . 2008; 52:2750-4. [PubMedCentral][PubMed 18411316]

697. van Burik JA, Hackman RC, Nadeem SQ et al. Nocardiosis after bone marrow transplantation: a retrospective study. Clin Infect Dis . 1997; 24:1154-60. [PubMed 9195074]

698. Garlando F, Bodmer T, Lee C et al. Successful treatment of disseminated nocardiosis complicated by cerebral abscess with ceftriaxone and amikacin: case report. Clin Infect Dis . 1992; 15:1039-40. [PubMed 1457635]

699. Garcia del Palacio JI, Martín Pérez I. Response of pulmonary nocardiosis to ceftriaxone in a patient with AIDS. Chest . 1993; 103:1925-6. [PubMed 8404142]

700. Unkle DW, Ricketti AJ, Cleri DJ et al. An HIV-infected patient with Nocardia asteroides bilateral pneumonia. AIDS Read . 2008; 18:566-8. [PubMed 19062401]

701. McPhee L, Stogsdill P, Vella JP. Nocardia farcinica pericarditis after kidney transplantation despite prophylaxis. Transpl Infect Dis . 2009; :. [PubMed 19508699]

702. Kilincer C, Hamamcioglu MK, Simsek O et al. Nocardial brain abscess: review of clinical management. J Clin Neurosci . 2006; 13:481-5. [PubMed 16678731]

708. Solomkin JS, Mazuski JE, Bradley JS et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis . 2010; 50:133-64. [PubMed 20034345]

716. Centers for Disease Control and Prevention (CDC). Cephalosporin susceptibility among Neisseria gonorrhoeae isolates--United States, 2000-2010. MMWR Morb Mortal Wkly Rep . 2011; 60:873-7. [PubMed 21734634]

717. Ohnishi M, Golparian D, Shimuta K et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother . 2011; 55:3538-45. [PubMedCentral][PubMed 21576437]

718. Chisholm SA, Alexander S, Desouza-Thomas L et al. Emergence of a Neisseria gonorrhoeae clone showing decreased susceptibility to cefixime in England and Wales. J Antimicrob Chemother . 2011; :. [PubMed 21846672]

719. Ison CA, Hussey J, Sankar KN et al. Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill . 2011; 16 [PubMed 21492528]

720. Unemo M, Golparian D, Hestner A. Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro Surveill . 2011; 16 [PubMed 21329645]

721. Ohnishi M, Saika T, Hoshina S et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis . 2011; 17:148-9. [PubMedCentral][PubMed 21192886]

722. Centers for Disease Control and Prevention (CDC). Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep . 2012; 61:590-4. [PubMed 22874837]

723. Allen VG, Mitterni L, Seah C et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA . 2013; 309:163-70. [PubMed 23299608]

724. Kirkcaldy RD, Bolan GA, Wasserheit JN. Cephalosporin-resistant gonorrhea in North America. JAMA . 2013; 309:185-7. [PubMed 23299612]

725. Olsen B, Pham TL, Golparian D et al. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011. BMC Infect Dis . 2013; 13:40. [PubMedCentral][PubMed 23351067]

726. Kirkcaldy RD, Zaidi A, Hook EW et al. Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010. Ann Intern Med . 2013; 158:321-8. [PubMed 23460055]

727. Goire N, Lahra MM, Ohnishi M et al. Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain. Euro Surveill . 2013; 18:20444. [PubMed 23594520]

728. Chow AW, Benninger MS, Brook I et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis . 2012; 54:e72-e112. [PubMed 22438350]

729. Wald ER, Applegate KE, Bordley C et al. Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years. Pediatrics . 2013; :. [PubMed 23796742]

730. Fenollar F, Puéchal X, Raoult D. Whipple's disease. N Engl J Med . 2007; 356:55-66. [PubMed 17,202456]

731. Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. Gastroenterology . 2010; 138:478-86; quiz 11-2. [PubMed 19879276]

732. Bures J, Kopácová M, Douda T et al. Whipple's Disease: Our Own Experience and Review of the Literature. Gastroenterol Res Pract . 2013; 2013:478349. [PubMed 23843784]

743. Gupta K, Hooton TM, Naber KG et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis . 2011; 52:e103-20. Updates may be available at IDSA website at www.idsociety.org. [PubMed 21292654]