Ceftriaxone is a semisynthetic, third generation cephalosporin antibiotic.1,16,104,105,106,165,171
Ceftriaxone is used for the treatment of acute otitis media (AOM) caused by Streptococcus pneumoniae , Haemophilus influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).1,310,311,312,313,427,428,429,458,614,683,750,751
When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate potassium as the drug of first choice for initial treatment.683,750,751 These experts recommend certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients.683,750,751 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
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 suggesting 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.535,613,683,751
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
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 , Streptococcus 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
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 .1,3,18,30,32,87,104,121,124,127,131,132,150,246,590,591
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 byβ-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
Ceftriaxone has been 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 has been 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 has been 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
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
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 ) that is 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 consisting 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 that is 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 is 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 is 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 that is 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 Ifendocarditis† involving prosthetic valves or other prosthetic material is caused by viridans group streptococci or S. gallolyticus that is 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
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 lower risk of nephrotoxicity and 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
Ceftriaxone has been used for the treatment of gastroenteritis† caused by Salmonella 299,440,752 or Shigella .401,402,753 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
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.217,299,440,752 These individuals include infants younger than 3 months of a individuals older than 50 years of age with suspected atherosclerosis; individuals with hemoglobinopathies, atherosclerosis or valvular or endovascular disease, significant joint disease, or chronic GI disease; and individuals who are immunocompromised because of malignancy, immunosuppressive therapy, HIV infection, or other immunosuppressive illness.217,440
When an anti-infective agent is considered necessary in an individual with Salmonella gastroenteritis, CDC, AAP, IDSA, and others recommend ceftriaxone, cefotaxime, a fluoroquinolone, ampicillin, amoxicillin, or co-trimoxazole, depending on susceptibility of the causative organism.197,217,299,440 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.752 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
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 option when anti-infectives are indicated for the treatment of Shigella infections.197,753
Infections caused by S. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives.753 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.440,753
Although an empiric regimen can be used initially when anti-infectives are indicated in the treatment of Shigella infections,753 in vitro susceptibility testing of clinical isolates is generally recommended because of increasing antimicrobial resistance.440,753 For infections caused by Shigella , IDSA and AAP recommend azithromycin, ciprofloxacin, or ceftriaxone as first-line agents.217,403,753 Alternative agents include oral ampicillin or co-trimoxazole for susceptible isolates.217,753 A fluoroquinolone should not be used if the ciprofloxacin MIC is ≥0.12 mcg/mL, even if the laboratory report identifies the isolate as susceptible.217,753 AAP recommends the use of oral antibiotics over parenteral treatment, except for in seriously ill patients, those with underlying immunodeficiencies, and patients unable to take oral medications.753
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
CDC, NIH, and IDSA also state that a short course of antibiotics (e.g., a 5-day regimen of ciprofloxacin) may be indicated in patients with HIV and CD4+ T-cell counts of 200-500 cells/mm3 who have diarrhea severe enough to compromise quality of life or ability to work.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
Ceftriaxone is used for the treatment of intra-abdominal infections caused by susceptible Escherichia coli , Klebsiella pneumoniae , Clostridium , or Peptostreptococcus .1,3,18,30,32,104,105,129,132,149 The drug also has been used for the treatment of various gynecologic infections, including pelvic inflammatory disease.1,3,18,30,32,125,292,344,397,398,459,460 Although the manufacturers state that ceftriaxone can be used for the treatment of intra-abdominal infections caused by Bacteroides fragilis ,1,3,18,30,32 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
Meningitis and Other CNS Infections
Ceftriaxone is used in neonates,104,140,142,144,243,249,250,292 children,80,87,104,130,139,140,141,142,143,144,187,243,245,246,249,250,257,258,259,270,272,418,750,751,754,755 and adults80,87,104,138,270,271,418 for the treatment of meningitis caused by susceptible Haemophilus influenzae , Neisseria meningitidis , or Streptococcus pneumoniae .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., Escherichia coli , Klebsiella †)18,30,32,104,133,156 or S. epidermidis .1,3,18,30,32
IV ceftriaxone with or without other anti-infectives (e.g., ampicillin, gentamicin, vancomycin) has been recommended for empiric treatment of meningitis†.292,343,418,419,468,471,475,750,751 For initial empiric therapy for suspected meningitis in non-neonates, AAP recommends combination therapy with ceftriaxone and vancomycin.750 For initial empiric therapy for suspected meningitis in neonates 8-28 days of age, AAP recommends combination therapy with ampicillin and cefotaxime with or without an aminoglycoside; alternatives to cefotaxime include ceftazidime or cefepime.750,751 For initial empiric therapy in neonates 0-7 days of age, AAP recommends combination therapy with ampicillin and gentamicin with or without a third or fourth generation cephalosporin.750 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 .197,243,418,475,750,751 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.111,242,323,333 Because susceptibility can no longer be assumed, S. pneumoniae isolates should be routinely tested for in vitro susceptibility.243,323,324,330,419,751 AAP states that children with bacterial meningitis presumed to be caused by S. pneumoniae should be treated with vancomycin in addition to ceftriaxone because of the possibility of resistant S. pneumoniae .750,751 AAP recommends cefotaxime over ceftriaxone in neonates with bacterial meningitis known or suspected to be caused by S. pneumoniae ; if cefotaxime is not available, ceftazidime or cefepime may be used in addition to vancomycin.751 For children with serious proven hypersensitivity reactions to third or fourth generation cephalosporins, a pediatric infectious diseases specialist should be consulted for consideration of the use of vancomycin plus either meropenem or rifampin.751 AAP recommends that an infectious diseases specialist be consulted for all pediatric patients with bacterial meningitis.751
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.475,751 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.418,475,751 If meningitis is caused by S. pneumoniae highly resistant to ceftriaxone (i.e., MIC ≥4 mcg/mL), 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).105,141,197,418,419,475,755 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.755 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.468,471,755
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.166,475,754 If a diagnosis of N. meningitidis meningitis is confirmed, AAP and other clinicians suggest treatment with penicillin G, ampicillin, ceftriaxone, or cefotaxime.166,197,418,475,754 Because β-lactamase-producing N. meningitidis has been reported in the US, meningococcal isolate susceptibility to penicillin should be determined before switching to penicillin or ampicillin.754 For patients with a life-threatening penicillin allergy characterized by anaphylaxis, AAP states that meropenem can be used with caution as the rate of cross-reactivity in penicillin-allergic adults is very low.754
Meningitis Caused by Enterobacteriaceae
Some clinicians recommend that meningitis caused by Enterobacteriaceae† (e.g., E. coli , K. pneumoniae †) be treated with a third generation cephalosporin (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
In infants 8-28 days of age with suspected S. agalactiae meningitis, AAP recommends ampicillin plus an extended-spectrum cephalosporin (e.g., cefotaxime, ceftazidime, cefepime).756 In infants 29-89 days of age, ceftriaxone plus vancomycin is recommended.756 Penicillin G or ampicillin is recommended if S. agalactiae is identified and the strain is susceptible.756 For infants with uncomplicated meningitis, 14 days of IV therapy is recommended, with longer courses of treatment for infants with prolonged or complicated cases.756
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
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
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., Streptococcus pneumoniae , Staphylococcus aureus ) or gram-negative bacteria (e.g., Haemophilus influenzae , H. parainfluenzae , Klebsiella pneumoniae , Escherichia coli , Enterobacter aerogenes , Proteus mirabilis , Serratia marcescens ).1,3,18,30,32,87,88,104,105,119,120,121,124,125,127,128,129,131,246,313,390,423,448,456,493,512,513,728 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
Ceftriaxone has been 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, the Infectious Diseases Society of America (IDSA) recommends amoxicillin and clavulanate potassium and the American Academy of Pediatrics (AAP) recommends either amoxicillin or amoxicillin and clavulanate potassium as the drugs 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
Ceftriaxone is recommended by the American Thoracic Society (ATS) and IDSA in certain combination regimens used for empiric treatment of community-acquired pneumonia (CAP) in hospitalized patients.512 The treatment regimen should be selected based on the most likely pathogens, local susceptibility patterns, and individual patient characteristics.512
Initial treatment for CAP generally is empiric and is based on selecting drugs that are effective against the major bacterial causes of the infection.512 Traditionally, these bacterial pathogens include S. pneumoniae , H. influenzae , Mycoplasma pneumoniae , S. aureus , Legionella species, Chlamydia pneumoniae , and Moraxella catarrhalis .512,751 The emergence of multidrug-resistant pathogens, including methicillin-resistant S. aureus (MRSA) and P. aeruginosa , requires separate recommendations when the risk of each of these pathogens is elevated.512 In addition to H. influenzae and M. catarrhalis (both of which frequently produce ß-lactamase), S. aureus and gram-negative bacilli are more common causes of CAP in patients with comorbidities, such as chronic obstructive pulmonary disease (COPD).512 Observational data suggest that inpatient and outpatient CAP are generally due to the same pathogens, except for Legionella and gram-negative bacilli, which are rarely documented in outpatient settings.512
Pretreatment sputum cultures are not routinely recommended in outpatients being treated for CAP.512 Pretreatment sputum cultures are recommended in hospitalized patients being treated for CAP who have severe CAP (especially if intubated), who are being empirically treated for MRSA or P. aeruginosa , who previously were infected with MRSA or P. aeruginosa (especially those with prior respiratory tract infection), and who were hospitalized and received parenteral antibiotics (whether during the hospitalization event or not) in the last 90 days.512
For empiric inpatient treatment of nonsevere CAP in adult patients without risk factors for MRSA or P. aeruginosa , IDSA and ATS recommend either combination therapy with a ß-lactam (ampicillin-sulbactam, cefotaxime, ceftriaxone, or ceftaroline) and a macrolide (azithromycin or clarithromycin) or monotherapy with a respiratory fluoroquinolone (levofloxacin or moxifloxacin).512 In patients who have contraindications to both macrolides and fluoroquinolones, an alternative option is combination therapy with a ß-lactam (ampicillin-sulbactam, cefotaxime, ceftaroline, or ceftriaxone) and doxycycline.512 The choice between these agents should be individualized based on the risks and benefits of the drugs, and also consider whether the patient has a history of C. difficile infection.512
For empiric inpatient treatment of severe CAP in adult patients without risk factors for MRSA or P. aeruginosa , IDSA and ATS recommend a ß-lactam plus a macrolide or a ß-lactam plus a respiratory fluoroquinolone.512 There is stronger evidence in favor of ß-lactam/macrolide combination therapy compared with ß-lactam/fluoroquinolone combination therapy.512
In inpatient pediatric patients, AAP recommends ceftriaxone as a treatment option for CAP suspected or proven to be caused by penicillin-nonsusceptible strains of pneumococcus, in patients with serious infections including empyema, and in patients not fully immunized with pneumococcal conjugate vaccines PCV13, PCV15, or PCV20.751
In pediatric inpatients in regions with high levels of penicillin-resistant pneumococcus, AAP recommends empiric treatment for CAP with ceftriaxone.750 If an atypical pathogen (e.g., Mycoplasma or Chlamydia species) is suspected, a macrolide should be added to the regimen.750 If MRSA is suspected, coverage with vancomycin, clindamycin, or linezolid should be added.750
In pediatric inpatients with CAP caused by pneumococci suspected or proven to be penicillin-nonsusceptible, in patients with serious infections including empyema, or in those not fully immunized with pneumococcal conjugate vaccines PCV13, PCV15, or PCV20, AAP recommends treatment with ceftriaxone or cefotaxime.751 Vancomycin should be added in patients with life-threatening infection.751 AAP states that patients with nonsusceptible isolates to penicillin (MIC ≥4.0 mcg/mL) or serious allergy to ß-lactam antimicrobials, treatment with clindamycin (if susceptible) or levofloxacin should be considered, assuming that concurrent meningitis has been excluded.751
Coverage for P. aeruginosa should be added in hospitalized patients with nonsevere or severe CAP who have had prior respiratory isolation of P. aeruginosa within the past year and in hospitalized patients with severe CAP who have undergone recent hospitalization requiring parenteral antibiotic treatment and who have locally validated risk factors for P. aeruginosa .512
Coverage for MRSA should be added in hospitalized patients with severe CAP who have had prior respiratory isolation of MRSA within the past year or who have undergone recent hospitalization and parenteral antibiotic treatment and have locally validated risk factors for MRSA.512
IDSA and ATS recommend that the duration of antibiotic therapy for CAP should be guided by a validated measure of clinical stability (resolution of vital sign abnormalities [heart rate, respiratory rate, blood pressure, oxygen saturation, and temperature], ability to eat, and normal mentation), and that antibiotic therapy should be continued until the patient achieves stability and for no less than a total of 5 days.512 Most patients will achieve clinical stability within the first 48-72 hours of antibiotic treatment.512 If therapy is initiated with parenteral antibiotics and patients are to be switched to oral antibiotics, either the same drug or a drug from the same class should be used.512
AAP recommends a duration of antibiotic therapy of 5 days for uncomplicated CAP with resolution of fever, tachypnea, and supplemental oxygen requirement.750 When tolerated, an early switch from parenteral therapy to oral therapy is recommended.750 The duration of therapy may be extended when CAP is complicated by empyema, necrotizing pneumonia, or pulmonary abscess.750 AAP states that because respiratory viruses cause the majority of CAP, especially in young children, antibiotic therapy may not be indicated for all patients with CAP.750
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 .1,3,18,30,32,87,104,105,120,121,124,125,131,246
Skin and Skin Structure Infections
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 , Serratia marcescens , Acinetobacter calcoaceticus , Bacteroides fragilis , or Peptostreptococcus .1,3,18,30,32,87,89,104,105,120,121,124,128,129,131,132
Although the manufacturers state that ceftriaxone can be used for the treatment of skin and skin structure infections caused by P. aeruginosa ,1,3,18,30,32 treatment failures have been reported when ceftriaxone was used alone in the treatment of urinary tract infections or respiratory tract infections caused by P. aeruginosa .104,124 Some of these failures occurred because superinfection with resistant strains of P. 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
Ceftriaxone has been recommended for use in multiple-drug anti-infective regimens for empiric treatment of necrotizing infections of the skin, fascia, andmuscle†.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
Ceftriaxone is used in adult and pediatric patients for the treatment of complicated and uncomplicated urinary tract infections caused by E. coli , K. pneumoniae , Morganella morganii , P. mirabilis , or P. vulgaris .1,3,18,30,32,82,91,104,119,120,121,124,125,127,128,129,131,246,455
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 , Providencia 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
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, erythromycin, chloramphenicol, clindamycin, third generation cephalosporins, and meropenem.197,292,382
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
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
Based on results of in vitro susceptibility tests indicating 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
A single IM dose of ceftriaxone has been used for the treatment of chancroid† (genital ulcers caused by H. ducreyi ).210,211,229,241,274,344,747,748
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.344,747,748
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
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
Gonorrhea and Associated Infections
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.1,3,18,30,32,81,90,114,115,116,117,118,221,225,292,336,344,746,747,748 Ceftriaxone is the drug of choice for the treatment of gonococcal infections in most patients.344,746,747,748 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.344,746,747
Currently, CDC, AAP, and other clinicians state that ceftriaxone is the drug of choice for gonococcal infections in the US.344,746,747,748 Although dual therapy with ceftriaxone and azithromycin was recommended in previous treatment guidelines and may have mitigated the emergence of reduced susceptibility to ceftriaxone in N. gonorrhoeae , concerns regarding potential harm to the microbiome and effects on other pathogens have caused the CDC and AAP to no longer recommend dual therapy for gonococcal infections.344,746,747 If chlamydia has not been excluded, CDC states that oral doxycycline (100 mg twice daily for 7 days) should be added to ceftriaxone.344,747
CDC recommends that healthcare providers treating gonorrhea remain vigilant for treatment failures (evidenced by persistent symptoms or a positive follow-up test despite treatment).344 N. gonorrhoeae with reduced susceptibility to ceftriaxone and/or cefixime or other cephalosporins have been reported in the US and elsewhere.344,716,717,718,719,720,721,722,723,724,725,726,727 If infection persists (treatment failure) and reinfection is unlikely, relevant clinical specimens should be obtained for culture (preferably with simultaneous nucleic acid amplification test [NAAT]) and in vitro susceptibility testing should be performed.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 (800-232-4636) 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.344,722
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 and AAP recommend treatment with a single IM dose of ceftriaxone (500 mg in patients weighing <150 kg and 1 g in patients ≥150 kg).344 In clinical trials, a single 250-mg IM dose of ceftriaxone was associated with a cure rate >99% in patients with uncomplicated urogenital and anorectal gonorrhea; however, a higher dose is likely necessary for isolates with elevated MICs.344 If chlamydia infection has not been excluded, patients also should be treated for chlamydia with oral doxycycline at a dosage of 100 mg twice daily for 7 days.344,747
If necessary because ceftriaxone is not available or cannot be used, CDC states that adults and adolescents can receive a single 800-mg dose of oral cefixime for the treatment of uncomplicated urogenital or anorectal gonorrhea.344,747 The oral cefixime regimen does not provide the high, sustained bactericidal blood concentrations provided by IM ceftriaxone.344
In adults and adolescents with cephalosporin allergy, CDC states that 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 this regimen.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 treatment regimen.344,746,747
Uncomplicated Pharyngeal Gonorrhea
For the treatment of uncomplicated gonorrhea of the pharynx† in adults and adolescents, CDC and AAP recommend treatment with a single IM dose of ceftriaxone (500 mg in patients weighing <150 kg and 1 g in patients ≥150 kg.344,746,747 If chlamydia infection has not been excluded, patients also should be treated for chlamydia with oral doxycycline at a dosage of 100 mg twice daily for 7 days.344,747
Pharyngeal gonococcal infections are more difficult to eradicate than cervical, urethral, or rectal infections.344,746 Ceftriaxone generally has been effective in the treatment of pharyngeal gonococcal infections;104,115,118,251,336,344,746,747 most other anti-infectives, including oral cephalosporins, do not reliably cure such infections.104,115,344 No reliable alternative treatments are available for pharyngeal gonorrhea.344 For patients with an anaphylactic or other severe reaction (e.g., Stevens Johnson syndrome) to ceftriaxone, CDC recommends consulting with an infectious disease specialist for an alternative treatment recommendation.344,747
A test-of-cure follow-up is recommended 7-14 days after treatment in patients with uncomplicated pharyngeal gonorrhea.344,746,747
The treatment of choice for gonococcal conjunctivitis† in adults and adolescents is a single 1-g IM dose of ceftriaxone.344,747 As an adjunct to anti-infective therapy, the infected eye can be irrigated once with sterile sodium chloride solution.344,747 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 IM or IV ceftriaxone 1 g every 24 hours.344 Alternatives for initial treatment include a multiple-dose regimen of IV cefotaxime (1 g every 8 hours) or IV ceftizoxime (1 g every 8 hours; not currently available in the US).344,747 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.344,747 If chlamydia infection has not been excluded, patients also should be treated for chlamydia with oral doxycycline at a dosage of 100 mg twice daily for 7 days.344
For the treatment of gonococcal meningitis† or gonococcal endocarditis†, CDC recommends that adults receive IV ceftriaxone 1-2 g every 24 hours.344,747 The parenteral regimen should be continued for 10-14 days in patients with meningitis and for at least 4 weeks in patients with endocarditis.344,747
Initial treatment of disseminated gonococcal infections should be undertaken in the hospital and 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 Treatment for disseminated gonococcal infections should be guided by the results of antimicrobial susceptibility testing.344
Ceftriaxone is a drug of choice for the treatment of acute epididymitis†.344,747,748 Acute epididymitis can be caused by sexually transmitted organisms (e.g., Chlamydia trachomatis , N. gonorrhoeae , or Mycoplasma genitalium ) or enteric organisms (i.e., Escherichia coli ).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 ).344,747,748
For empiric treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea†, CDC and AAP recommend that adults and adolescents receive a single 500-mg (1 g in patients weighing ≥150 kg) dose of IM ceftriaxone given in conjunction with a 10-day regimen of oral doxycycline 100 mg twice daily.344,747,748
For empiric treatment of acute epididymitis most likely caused by sexually transmitted chlamydia, gonorrhea, and enteric bacteria†, CDC and AAP recommend that adults and adolescents receive a single 500-mg (1 g in patients weighing ≥150 kg) dose of IM ceftriaxone given in conjunction with a 10-day regimen of oral levofloxacin 500 mg once daily for 10 days.344,747,748 CDC states that levofloxacin 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.344,747
For presumptive treatment of acute proctitis† prior to availability of diagnostic laboratory test results, CDC and AAP recommend that adults and adolescents receive a single IM dose of ceftriaxone (500 mg in patients weighing <150 kg and 1 g in patients weighing ≥150 kg) given in conjunction with a 7-day regimen of oral doxycycline (100 mg twice daily).344,747,748
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.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).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.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.344,746
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 (20-50 mg/kg, maximum 250 mg) for parenteral prophylaxis † and presumptive treatment of gonorrhea†.344,746,747 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.344,746 Ceftriaxone should be administered cautiously to neonates with hyperbilirubinemia, especially those born prematurely.344 Cefotaxime (100 mg/kg IV or IM as a single dose) can be administered for those neonates unable to receive ceftriaxone because of simultaneous administration of IV calcium.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 (25-50 mg/kg, maximum 250 mg).344,746,747 Ceftriaxone should be administered cautiously to neonates with hyperbilirubinemia, especially those born prematurely.344 Cefotaxime (100 mg/kg IV or IM as a single dose) can be administered for those neonates unable to receive ceftriaxone because of simultaneous administration of IV calcium.344,746,747
As an adjunct to parenteral treatment of gonococcal ophthalmia neonatorum, one-time lavage of the neonate's infected eye(s) with sterile sodium chloride solution may be considered.344,747 Topical anti-infectives are inadequate for the treatment of gonococcal ophthalmia neonatorum and are unnecessary when appropriate systemic anti-infective therapy is given.344,746
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 should be hospitalized and evaluated for signs of disseminated infection (e.g., sepsis, arthritis, meningitis).344 CDC and AAP recommend that infants with gonococcal ophthalmia neonatorum be managed in consultation with an infectious disease specialist.344,746
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).292,344,746 If disseminated gonococcal infection is present, CDC and AAP recommend a multiple-dose regimen of IV or IM ceftriaxone (25-50 mg/kg, maximum 250 mg, once daily) or IV or IM cefotaxime (25 mg/kg every 12 hours); the recommended duration of therapy is 7 days or, if meningitis is documented, 10-14 days.344,746 While either ceftriaxone or cefotaxime can be used for the treatment of disseminated gonococcal infections in neonates,344,746 ceftriaxone is contraindicated in certain neonates.1,18,30,32,344,746
Gonococcal Infections in Infants and Children
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 ceftriaxone.344,746,748 In children weighing >45 kg, a single 500-mg IM dose of ceftriaxone is recommended.344,748 In infants and children weighing ≤45 kg, the recommended single dose of IV or IM ceftriaxone is 25-50 mg/kg (maximum 250 mg).344,748 AAP states that if chlamydial infection has not been excluded, patients should be treated for C. trachomatis infection with either oral doxycycline, azithromycin, levofloxacin, or erythromycin, depending on the patient's weight.746
CDC states that adolescents with uncomplicated gonorrhea should receive the same treatment regimens recommended for adults.344
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.344,746 In children weighing >45 kg, the recommended dosage of ceftriaxone is 50 mg/kg (maximum 2 g) IM or IV once daily (every 24 hours) for 7 days.344 In infants and children weighing ≤45 kg, the recommended dosage of ceftriaxone is 25-50 mg/kg (maximum 250 mg) once daily (every 24 hours) for 7 days.344
CDC states that adolescents with disseminated gonococcal infections should receive the same treatment regimens recommended for adults.344
Prophylaxis in Sexual Assault Victims
A single dose of IM ceftriaxone 500 mg (or 1 g in patients weighing ≥150 kg) is used in conjunction with oral doxycycline (100 mg twice daily for 7 days) and oral metronidazole (500 mg twice daily for 7 days) for empiric anti-infective prophylaxis in adult or adolescent victims of sexual assault†.344,749 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, doxycycline, and metronidazole) 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 AAP does not recommend routine empiric prophylaxis for prepubertal children who have been sexually assaulted or abused due to the low incidence of sexually transmitted infections in such patients, the low risk of spread to the uterus, fallopian tubes, and ovaries, and the higher likelihood of reliable follow-up.749
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.344 In addition, vaccination with human papillomavirus (HPV) vaccine is recommended for previously unvaccinated or incompletely vaccinated female and male assault victims 9-26 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
Ceftriaxone has been used in the treatment of severe leptospirosis† caused by Leptospira .690,694,695,758 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, myocarditis, cardiac arrhythmias, pneumonitis, and hemodynamic collapse (Weil syndrome).292,691,693,758
Penicillin G generally has been considered the drug of choice for the treatment of moderate to severe leptospirosis,197,690,691,695,758 and doxycycline has been used in less severe infections.197,758 Other anti-infectives recommended for the treatment of severe leptospirosis include cephalosporins (ceftriaxone, cefotaxime), aminopenicillins (ampicillin, amoxicillin), tetracyclines (doxycycline, tetracycline), or macrolides (azithromycin).197,292,691,693,694,695,758
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
Ceftriaxone is used in the treatment of Lyme disease†.197,329,342,357,358,359,361,362,363,364,365,366,367,481,492,744,745 The Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), American College of Rheumatology (ACR), American Academy of Pediatrics (AAP), and other clinicians recommend IV ceftriaxone as a drug of choice for the treatment of neurologic Lyme disease†, Lyme carditis†in hospitalized patients, and Lyme arthritis†that has not responded to oral antibiotics.329,342,357,358,359,361,362,363,364,365,366,367,481,492,744,745
Lyme disease is a tick-borne spirochetal disease.207,261,314,329,481,497,744,745 In the US, Lyme disease is caused by the spirochete Borrelia burgdorferi (or, in rare cases, Borrelia mayonii ), which is transmitted by the bite of Ixodes scapularis or I. pacificus ticks.207,261,314,329,481,497,744,745
Appropriate antibiotic treatment shortens the duration of erythema migrans and usually prevents the development of late sequelae of Lyme disease.745 AAP states that children with early Lyme disease treated with effective antimicrobial agents rarely develop late manifestations of Lyme disease.744 According to treatment guidelines from IDSA/AAN/ACR as well as guidelines from AAP, oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil) are the preferred treatment for Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations or advanced atrioventricular (AV) heart block.279,329,353,356,357,358,359,361,362,363,365,366,367,481,744,745 For patients unable to take either doxycycline or ß-lactam antibiotics, the preferred second-line treatment for erythema migrans is azithromycin.329,744,745 The recommended duration of treatment is 10 days for doxycycline, 14 days for amoxicillin or cefuroxime axetil, and 7 days for azithromycin.329,744,745 Although doxycycline generally is not recommended for pediatric patients <8 years of age, AAP states that the drug is considered safe when used for ≤21 days in pediatric patients of any age.744,745 AAP states that the choice of oral antibiotic for treatment of erythema migrans should be individualized based on the presence of neurologic disease (for which doxycycline is the drug of choice), drug allergy history, likelihood of coinfection with other bacteria (e.g., Anaplasma phagocytophilum or Ehrlichia muris -like agent, neither of which is sensitive to ß-lactam antibiotics), adverse effect profile, frequency of administration, ability to minimize sun exposure, and presence of symptoms difficult to distinguish from Staphylococcus aureus cellulitis (doxycycline is effective against most strains of Staphylococcus aureus , including methicillin-resistant strains).744
Ceftriaxone is a drug of choice for the treatment of acute neurologic Lyme disease†.279,329,353,356,357,358,359,361,362,363,365,366,367,481,744,745 According to treatment guidelines from IDSA/AAN/ACR, in patients with Lyme disease-associated meningitis, cranial neuropathy, radiculoneuropathy, or with other peripheral nervous system manifestations, the recommended treatment is parenteral therapy with ceftriaxone, cefotaxime, or penicillin G, or oral therapy with doxycycline.329 AAP states that a growing body of evidence suggests that oral doxycycline is effective for the treatment of Lyme disease-associated meningitis and may be used as an alternative to hospitalization and parenteral ceftriaxone or penicillin G therapy in pediatric patients who are well enough to be treated as outpatients.744 The choice of antibiotic, including route of administration, should be individualized based on drug allergy history, adverse effect profile, ease of administration, ability to tolerate oral medications, and compliance factors.329 The route of therapy may be changed from IV to oral during treatment in patients who have experienced clinical improvement.329,745 The recommended duration of treatment is 14-21 days.329,744,745
In patients with acute neurologic Lyme disease with parenchymal involvement of the brain or spinal cord, IDSA/AAN/ACR state that IV antibiotic treatment for the entire course is preferred.329,745 In patients with Lyme disease and facial nerve palsy†, IDSA/AAN/ACR provide no recommendation concerning the use of corticosteroids in addition to antibiotic treatment,329 and AAP states that the risks and benefits of concurrent steroid treatment in such patients are unknown;744 AAP states that doxycycline is the preferred oral antibiotic treatment for pediatric patients of any age with Lyme disease-associated facial palsy.744
Ceftriaxone is the drug of choice when a parenteral regimen is indicated for the treatment of Lyme carditis†.329,497,744,745 In outpatients with Lyme carditis, IDSA/AAN/ACR recommend treatment with oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) over IV antibiotics.329,745 In patients with or at high risk of severe cardiac complications, including those with a PR interval >0.3 seconds, other arrhythmias, or clinical manifestations of myopericarditis, IDSA/AAN/ACR recommend hospitalization with continuous ECG monitoring and treatment with IV ceftriaxone over oral antibiotics; upon clinical improvement, patients may be switched to oral antibiotics to complete the recommended 14-21 days of treatment.329,745 For patients with symptomatic bradycardia due to Lyme carditis that cannot be managed medically, IDSA/AAN/ACR recommend temporary pacing modalities rather than implanting a permanent pacemaker.329
In pediatric patients with Lyme disease associated with atrioventricular heart block or carditis, AAP recommends oral treatment with doxycycline, amoxicillin, or cefuroxime axetil for 14 days (range: 14-21 days) or IV treatment with ceftriaxone for 14 days (range: 14-21 days for a hospitalized patient).744,745 Oral antibiotics may be substituted for IV treatment when the patient is stabilized or discharged from the hospital to complete the recommended 14-21 days of treatment.744,745 AAP states that azithromycin has not been sufficiently studied for manifestations of Lyme disease other than erythema migrans744
Ceftriaxone is the drug of choice when a parenteral regimen is indicated for the treatment of Lyme arthritis†.329,497,498,744,745 In patients with Lyme disease-associated arthritis, IDSA/AAN/ACR and AAP recommend initial treatment with a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil).329,744,745 In patients who experience a partial response to an initial course of treatment, the choice of whether to observe the patient or initiate a second course of antibiotic treatment should be made based on consideration of other causes of joint swelling, medication adherence, duration of arthritis before initial treatment, degree of synovial proliferation versus joint swelling, patient preferences, and cost.329 A second course of oral antibiotics for up to 1 month may be a reasonable alternative for patients in whom synovial proliferation is modest compared with joint swelling and for those who prefer repeating a course of oral antibiotics before considering IV antibiotic therapy.329 In patients with minimal or no response (moderate to severe joint swelling with minimal reduction of the joint effusion) to an initial 28-day course of oral antibiotic, IDSA/AAN/ACR and AAP recommend a 2- to 4-week course of IV ceftriaxone over a second course of oral antibiotics.329,744,745
In patients who have failed one course of oral antibiotics and one course of IV antibiotics, IDSA/AAN/ACR suggest referral to a rheumatologist or other trained specialist for consideration of the use of disease-modifying antirheumatic drugs (DMARDs), biologic agents, intra-articular steroids, or arthroscopic synovectomy.329 IDSA/AAN/ACR state that antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV antibiotic therapy.329
Persistent Symptoms Following Lyme Disease Treatment
For patients who have persistent or recurring nonspecific symptoms such as fatigue, pain, or cognitive impairment following recommended treatment for Lyme disease†, but who lack objective evidence of reinfection or treatment failure, IDSA/AAN/ACR and AAP recommend against additional antibiotic therapy.329,744,745 Several double-blind, randomized, placebo-controlled trials have found that retreatment with additional antimicrobial agents for patients with residual posttreatment subjective symptoms of Lyme disease may be associated with harm and does not offer benefit.744 However, retreatment is appropriate in patients who experience subsequent acute infections caused by B. burgdorferi .744
Neisseria meningitidis Infections
Ceftriaxone is used in the treatment of invasive infections caused by N. meningitidis 1,3,18,30,32,166,754 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†.166,376,754
For suspected meningococcal disease, including presumptive N. meningitidis , the American Academy of Pediatrics (AAP) and Infectious Diseases Society of America (IDSA) recommend a third generation cephalosporin (ceftriaxone or cefotaxime) for initial empiric treatment.418,754 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.754 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.166,376,754 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 patients with invasive meningococcal disease is an important means of preventing secondary cases in household and other close contacts.166,376,754,759 Recommended regimens for chemoprophylaxis against meningococcal disease include a single dose of IM ceftriaxone, a 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).166,376,754 These regimens are all 90-95% effective and considered acceptable for chemoprophylaxis.166,376
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.376 A decision to administer chemoprophylaxis to close contacts of an individual with invasive meningococcal disease is based on the degree of risk.376 Throat and nasopharyngeal cultures are not useful in determining the need for chemoprophylaxis and may unnecessarily delay administration of the regimen.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.166,376,754 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.166,292,376,754 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).166,292,376,754
Chemoprophylaxis is not routinely recommended for contacts of patients with invasive meningococcal disease who are considered at low risk of infection.754 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.754 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.166,376,754 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.166,376,754 If high-risk exposure to a new index case occurs more than 2 weeks after initial chemoprophylaxis, additional chemoprophylaxis is indicated.166
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.376,754,759 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.376,759 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.376,759 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.376,759
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.292,376,759
Ceftriaxone has been used for the treatment of nocardiosis† caused by Nocardia .197,697,698,699,700,701,702,763
Co-trimoxazole (fixed combination of sulfamethoxazole and trimethoprim) usually is considered the drug of choice for the treatment of mild nocardiosis.197,763 If the infection does not respond to co-trimoxazole, a fluoroquinolone or a carbapenem may be considered; however, most Nocardia species are resistant to ertapenem.763 Other agents with activity against specific Nocardia species include clarithromycin ( N. nova ) and amoxicillin and clavulanate ( N. brasiliensis and N. abscessus complex).763
For patients with serious Nocardia infections (pulmonary infection, disseminated disease, CNS involvement) or for Nocardia infections in immunocompromised patients, combination therapy is recommended.763 AAP recommends initial treatment with co-trimoxazole, amikacin, and either linezolid, imipenem, or meropenem until susceptibility information is available.763 Ceftriaxone is considered an alternative agent; however, resistance has been noted for many strains of N. farcinica , N. transvalensis complex, and N. otitidiscaviarum complex.763 AAP states that immunocompromised patients and patients with severe disease should be treated for 6-12 months and for at least 3 months after apparent cure.763 Patients with HIV may need longer treatment; in the absence of immune reconstitution, lifelong suppressive therapy should be considered.763
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.763
Ceftriaxone is used for the treatment of pelvic inflammatory disease (PID) caused by Neisseria gonorrhoeae .1,3,18,30,32,292,344,397,398,460,747,748 Ceftriaxone, like other cephalosporins, generally is inactive against Chlamydia trachomatis and should not be used alone in the treatment of PID.1,3,18,30,32,344
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 C. trachomatis ; however, organisms that can be part of the normal vaginal flora (e.g., anaerobic bacteria, Gardnerella vaginalis , Haemophilus influenzae , enteric gram-negative bacilli, Streptococcus agalactiae ) or mycoplasma (e.g., Mycoplasma hominis , Mycoplasma genitalium , Ureaplasma urealyticum ) may be involved.344,345,397,398,747,761 Cytomegalovirus and Trichomonas vaginalis also may be involved.344 PID is treated with an empiric regimen that provides broad-spectrum coverage.344,397,398,747,761 The regimen should be effective against N. gonorrhoeae and C. trachomatis and also probably should be effective against anaerobes.344,398,399,747,761 The optimum empiric regimen for the treatment of PID has not been identified; the long-term outcome of early treatment for subclinical PID also is unknown.344 A variety of parenteral and oral regimens has been shown to achieve clinical and microbiologic cure in randomized studies with short-term follow-up.397,399,344
When a parenteral regimen is indicated for the treatment of PID, CDC, AAP, and other clinicians generally recommend a 3-drug regimen of ceftriaxone (1 g IV every 24 hours) given in conjunction with doxycycline (100 mg IV or orally every 12 hours) and metronidazole (500 mg IV or orally every 12 hours) or 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).344,399,747,748 While certain other parenteral cephalosporins (e.g., cefotaxime, ceftizoxime) 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; if these drugs are used, the addition of metronidazole (in addition to doxycycline) should be considered.344
Additional alternative parenteral regimens recommended by CDC, AAP, and other clinicians include a 2-drug regimen of ampicillin-sulbactam (3 g IV every 6 hours) 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; a regimen of 3-5 mg/kg once daily can be substituted).344,747,748
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 (doxycycline 100 mg twice daily and metronidazole 500 mg twice daily) can be considered to complete 14 days of treatment.344,747 If tubo-ovarian abscess is present, at least 24 hours of inpatient observation is recommended.344
In women with mild to moderately severe acute PID, CDC, AAP, and other clinicians state that an IM and oral regimen can be considered since clinical outcomes with these regimens are similar to IV regimens in such patients.344,747,761 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, AAP, and other clinicians recommend 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 and oral metronidazole.344,747,748 The optimal cephalosporin is unclear; although cefoxitin usually has better anaerobic coverage, ceftriaxone has better coverage against N. gonorrhoeae .344
Because of the emergence of quinolone-resistant N. gonorrhoeae , regimens including a quinolone agent are not recommended for PID treatment; however, if the patient has cephalosporin allergy, the community prevalence and individual risk for gonorrhea are low, and follow-up is likely, CDC and other clinicians state that alternative therapy can be considered.344,747 Recommended alternative regimens in such situations include either a 2-drug regimen of levofloxacin (500 mg orally once daily) or moxifloxacin (400 mg orally once daily) in conjunction with metronidazole (500 mg orally twice daily for 14 days) or a 2-drug regimen of azithromycin (500 mg IV daily for 1-2 doses, followed by 250 mg orally daily) in combination with metronidazole (500 mg twice daily) for 12-14 days.344,747,748
Ceftriaxone may be effective for the treatment of relapsing fever† caused by Borrelia recurrentis ;264 however, other drugs (e.g., doxycycline, penicillin G) are generally considered the drugs of choice for the treatment of the disease.197,762 Second-line agents include erythromycin and azithromycin.762 AAP states that treatment with IV antibiotics such as penicillin or ceftriaxone is preferred for pregnant patients, when CNS involvement is present, or when oral therapy is not well tolerated.762
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.344,350,440,747,748,764 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.344,350,440,747,764 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.344,440,747,764
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.344 Although cross-sensitivity between penicillin and ceftriaxone can occur, CDC states that the risk for cross-reactivity between penicillin and third generation cephalosporins is considered negligible.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 addition, CDC, National Institutes of Health (NIH), and the Infectious Diseases Society of America (IDSA) state that the efficacy of non-penicillin alternatives has not been well evaluated in people with HIV and should be undertaken only with close clinical and serologic monitoring.440
In certain circumstances 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
Typhoid Fever and Other Invasive Salmonella Infections
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.167,188,267,406,407,408,409,410,752,765,766 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.410,505,590,752
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) have been 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 and CDC state that most typhoid fever infections diagnosed in the US are not susceptible to fluoroquinolones and that fluoroquinolones should not be used as empiric therapy.752,766 AAP states that ceftriaxone is a drug of choice for empiric treatment of enteric fever pending results of in vitro susceptibility tests.752 Strains of S. typhi resistant to ceftriaxone have been reported rarely in the US.405,752
Travel history and regional antibiotic resistance patterns should be considered carefully when selecting empiric antibiotic therapy for enteric fever.752,765,766 An epidemic of extensively drug-resistant (XDR) S. Typhi disease with resistance to ceftriaxone, ampicillin, ciprofloxacin, and co-trimoxazole has been reported in Pakistan; isolates have been susceptible only to azithromycin and carbapenems.752,765,766 XDR Typhi infections also have been reported rarely in US patients without a recent history of international travel.752,766 For enteric fever caused by S. Typhi that is known or suspected to be multidrug resistant (but not XDR), AAP recommends empiric therapy with a parenteral third generation cephalosporin or azithromycin.752 Because of the risk of ceftriaxone resistance, azithromycin or a carbapenem should be considered if the patient has traveled to Pakistan or Iraq in the 30 days before symptom onset.752 CDC states that clinicians should consider empiric treatment with a carbapenem (particularly for severe or complicated illness) or azithromycin for suspected typhoid fever in patients who did not travel out of the US as well as for those who traveled to Pakistan or Iraq within 30 days of onset of infection.766 According to CDC, ceftriaxone remains an appropriate empiric treatment option for patients who traveled to countries other than Pakistan and Iraq within the last 30 days.766 Clinicians should adjust treatment based on results of susceptibility testing.766 Patients with XDR Typhi infection who do not respond to carbapenem alone may benefit from the addition of azithromycin.766
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
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 with CNS involvement.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
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., P. 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
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
Ceftriaxone has been used perioperatively to reduce the incidence of infection in patients undergoing certain contaminated or potentially contaminated surgical procedures,1,18,30,32 including biliary tract procedures (e.g., cholecystectomy),1,18,30,32,147,152,294,295,296,297,298,374,449 colorectal procedures,374 intra-abdominal surgery,152,413 or vaginal or abdominal hysterectomy,1,18,30,32,154 and in those undergoing certain clean surgical procedures in which the development of infection at the surgical site would represent a serious risk,1,18,30,32 including coronary artery bypass,1,18,30,32 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
Ceftriaxone sodium is administered by IV infusion1,3,18,30,32 or deep IM injection.1
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.1,3,18,30,32,507,511,529
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).1,3,18,30,32,507,510,511,529 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).1,3,18,30,32,529
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.1,18,30,529
Patients receiving ceftriaxone should be adequately hydrated.1,3,18,32
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 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 Ceftriaxone solutions for IV infusion containing 10-40 mg/mL are recommended; however, lower concentrations may be used.1
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.1,18 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.1,18 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.1,18 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.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.1,18 Frozen solutions of ceftriaxone sodium should be thawed at room temperature;1,18 once thawed, unused portions should be discarded and should not be refrozen.1,18
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 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
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, the solution should be allowed to reach room temperature prior to administration.3 The Duplex® drug delivery system 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 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 The reconstituted 100 mg/mL solution should be further diluted without delay; any unused portions of the reconstituted solution should be discarded after 4 hours
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 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 (Galaxy®) .30 Solutions in contact with this plastic 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.1,18,30,32 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.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.1,18,32
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.1,18,30,32
The manufacturers recommend that intermittent IV infusions of ceftriaxone sodium be administered over 30 minutes (except in neonates).1,3,18,30,32
In neonates, the manufacturers recommend that intermittent IV infusions of ceftriaxone be given over 60 minutes.1,18,32
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 More dilute solutions of the drug may be used for IM injection if required.1 Do not use diluents containing calcium (e.g. Ringer's/lactated Ringer's injection, Hartmann's injection) to reconstitute or further dilute ceftriaxone because a precipitate can form.1,3,18,30,32,507,511,529
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
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 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
IM injections of ceftriaxone should be made deeply into a large muscle mass, using usual techniques and precautions.1
Dosage of ceftriaxone sodium is expressed in terms of ceftriaxone1,3,18,30,32 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
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.757
For pediatric patients beyond the neonatal period, AAP recommends a ceftriaxone dosage of 50-75 mg/kg once daily (maximum 1 g/day) for the treatment of infections other than CNS infections or endocarditis or a dosage of 100 mg/kg daily (maximum 4 g/day) given in 1 or 2 doses for the treatment of CNS infections or endocarditis.757
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.1,18,30,32 The maximum dosage recommended by the manufacturers for pediatric patients is 2 g daily.1,18,30,32
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).1,32
For initial treatment of AOM, AAP recommends a ceftriaxone dosage of 50 mg/kg daily (maximum 1 g/day) given IM or IV for 1 to 3 days†.683,757 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
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
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 Therapy and its duration should be adjusted depending on stool microbiology results and antibiotic sensitivity testing.440 If no pathogen is identified and the patient recovers quickly, a treatment duration of 5 days is considered reasonable.440
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.1,3,18,30,32,123,130,140,142,143,187,243,757 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 In neonates, AAP recommends a dosage of 50 mg/kg once every 24 hours.757
While 7-10 days or 5-7 days of anti-infective therapy may be adequate for the treatment of uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis , respectively, 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 † ).418,475,750 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, 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
If ceftriaxone is used in children for the treatment ofsevere acute bacterial rhinosinusitis† requiring hospitalization, IDSA recommends a dosage of 50 mg/kg daily given IV in divided doses every 12 hours.728
If ceftriaxone is used for the treatment of community-acquired pneumonia (CAP) in pediatric patients, AAP recommends a dosage of 50-75 mg/kg once daily (maximum 1 g daily).757 In neonates, AAP recommends a ceftriaxone dosage of 50 mg/kg every 24 hours.757 A treatment duration of 5 days is recommended for uncomplicated cases with clinical improvement (i.e., resolution of fever, tachypnea, supplemental oxygen requirement); a longer duration of treatment is recommended for complicated cases (e.g., empyema, necrotizing pneumonia, or pulmonary abscess).750
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
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.748
Gonococcal Infections in Neonates
When ceftriaxone is used for parenteral prophylaxis † or presumptive treatment of gonorrhea† in neonates born to mothers with gonorrhea, CDC recommends that a single dose of 20-50 mg/kg (maximum 250 mg) of the drug be given IM or IV at birth.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 250 mg) of ceftriaxone.344,746,747
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.344,746 If meningitis is documented, ceftriaxone should be continued for 10-14 days.344,746
Gonococcal Infections in Infants and Children
CDC and AAP recommend 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 250 mg IM) and that those weighing more than 45 kg receive a single 500-mg IM dose (1-g in patients weighing ≥150 kg) of ceftriaxone.344
For the treatment of gonococcal bacteremia or arthritis in children, CDC recommends that those weighing 45 kg or less receive IM or IV ceftriaxone in a dosage of 50 mg/kg daily every 24 hours (maximum 2 g daily) for 7 days and that those weighing more than 45 kg receive an IM or IV ceftriaxone dosage of 1 g every 24 hours for 7 days.344
Gonorrhea and Associated Infections in Adolescents
For the treatment of uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea, CDC and AAP recommend that adolescents receive a single 500-mg (1-g in patients weighing ≥150 kg) IM dose of ceftriaxone.344,748
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.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 24 hours.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 empiric anti-infective prophylaxis for gonorrhea, chlamydia, and trichomoniasis in adolescent sexual assault victims†, CDC and AAP recommend that a single 500-mg IM dose of ceftriaxone (1-g in patients weighing ≥150 kg) be given in conjunction with oral doxycycline (100 mg twice daily for 7 days) and, in females, metronidazole (500 mg twice daily for 7 days).344,749
If IV ceftriaxone is used for the treatment of acute Lyme disease† in children, the American Academy of Pediatrics (AAP) recommends a dosage of 50-75 mg/kg (up to 2 g) once daily for 14-21 days.744,745
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, AAP 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 for hospitalized patients).744,745 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.744,745
When a parenteral regimen is indicated for the treatment of Lyme arthritis†when arthritis has not responded to an oral regimen, AAP recommends that children receive IV ceftriaxone in a dosage of 50-75 mg/kg (up to 2 g) once daily for 14-28 days.744,745
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.376,754
When ceftriaxone is used to treat meningitis in pediatric patients, an initial dose of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily (up to 4 g daily) given as a single daily dose or in equally divided doses every 12 hours is recommended by manufacturers.1,3,18,30,32 Some clinicians recommend 80-100 mg/kg daily (up to 4 g daily) given as a single daily dose or in divided doses every 12 hours.245,249,250,259,418,471 The usual duration of treatment is 7-14 days;1 the American Academy of Pediatrics (AAP) states that 5-7 days may be adequate for meningococcal disease.750
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 500-mg IM dose (1-g in patients weighing ≥150 kg) of ceftriaxone followed by a 14-day regimen of doxycycline (100 mg orally twice daily) and metronidazole (500 mg orally twice daily).344,747 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
When parenteral treatment is indicated for PID, adolescents may receive ceftriaxone 1 g IV every 24 hours in conjunction with doxycycline (100 mg IV or orally every 12 hours) and metronidazole (500 mg IV or orally every 12 hours) for 14 days.344,747,748 Transition to oral therapy (with doxycycline and metronidazole) to complete 14 days of treatment usually can be initiated within 24 to 48 hours of clinical improvement.344,761
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.764 If ceftriaxone is used in neonates for the treatment of congenital syphilis, CDC states that neonates may receive a ceftriaxone dosage of 50-75 mg/kg IV every 24 hours for 10-14 days.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.344,764
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 g IM or IV once daily for 10 days.344,747,764 Some clinicians suggest that this ceftriaxone dosage also can be used as an alternative in penicillin-allergic nonpregnant adolescents with early latent syphilis.747,764
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 1-2 g IM or IV daily for 10-14 days based on limited data.344,764
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
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 relapse.404,408 AAP recommends a duration of treatment of at least 7-10 days of treatment for uncomplicated disease.752 Immunocompromised patients may require longer duration of treatment as well as retreatment.752
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, AHA recommends that children receive a single dose of 50 mg/kg given IV or IM 30-60 minutes prior to the procedure.451
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.1,3,18,30,32,87,89,91,104,119,120,125,127,128,129,131
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.1,3,18,30,32
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
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 withuncomplicated 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, 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
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 Therapy and its duration should be adjusted depending on stool microbiology results and antibiotic sensitivity testing.440 If no pathogen is identified and the patient recovers quickly, a treatment duration of 5 days is considered reasonable.440
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 bysusceptible 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, 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
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
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
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, CDC recommends that adults should receive a single 500-mg IM dose (1-g dose in patients weighing ≥150 kg) of ceftriaxone.344,747 The manufacturers recommend a single 250-mg IM dose of ceftriaxone.1,32
For the treatment of gonococcal conjunctivitis†, adults should receive a single 1-g IM dose of ceftriaxone.344,747
For the treatment of gonococcal arthritis and arthritis-dermatitis syndrome†, CDC recommends that adults receive 1 g of ceftriaxone IV or IM once daily.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.344,747
For the treatment of gonococcal meningitis† or gonococcal endocarditis†, CDC recommends that adults receive 1-2 g of ceftriaxone IV every 24 hours.344 Ceftriaxone should be continued for 10-14 days in those with meningitis and for at least 4 weeks in those with endocarditis.344,747
For presumptive treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea†, adults should receive a single 500-mg IM dose of ceftriaxone (1-g dose in patients weighing ≥150 kg) given in conjunction with doxycycline (100 mg orally twice daily for 10 days).344,747
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 500-mg IM dose of ceftriaxone (1-g dose in patients weighing ≥150 kg) given in conjunction with levofloxacin (500 mg orally once daily for 10 days).344,747
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
For empiric anti-infective prophylaxis for gonorrhea, chlamydia, and trichomoniasis in adult sexual assault victims†, CDC recommends that a single 500-mg IM dose of ceftriaxone (1-g dose in patients weighing ≥150 kg) be given in conjunction with doxycycline (100 mg twice daily for 7 days).344 In male survivors of sexual assault, CDC recommends a 2-drug regimen omitting metronidazole.344
For the treatment of severe leptospirosis†, adults have received ceftriaxone in a dosage of 1 g IV once daily for 7 days.690
If ceftriaxone is used for the treatment of acute neurologic Lyme disease† in adults, IDSA/AAN/ACR and other clinicians recommend a dosage of 2 g IV once daily for 14-21 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 Lyme disease, IDSA/AAN/ACR and other clinicians recommend a ceftriaxone dosage of 2 g IV once daily for 14-21 days.279,290,329,357,359,361,362,366,497,745 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.329,745
When a parenteral regimen is indicated for the treatment of Lyme arthritis† when arthritis has not responded to an oral regimen, IDSA/AAN/ACR and other clinicians recommend that adults receive a ceftriaxone dosage of 2 g IV once daily for 14-28 days.279,290,329,357,359,361,362,366,497,745
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 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 others suggest a dosage of 4 g daily 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 N. meningitidis , at least 10-14 days of therapy is suggested for complicated cases.418,475
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 500-mg (1-g in patients weighing ≥150 kg) IM dose of ceftriaxone followed by a 14-day regimen of doxycycline (100 mg orally twice daily) and oral metronidazole (500 mg twice daily).344,747 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
For the treatment of PID when parenteral treatment is indicated, adults may receive ceftriaxone 1 g IV every 24 hours in conjunction with doxycycline (100 mg IV or orally every 12 hours) and metronidazole (500 mg IV or orally every 12 hours).344,747
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 g IM or IV once daily for 10 days.344 Some clinicians suggest that this ceftriaxone dosage also can be used as an alternative in penicillin-allergic nonpregnant adults with early latent syphilis.345,350,440,747
If ceftriaxone is used as an alternative to IV penicillin G for the treatment of neurosyphilis† in penicillin-allergic nonpregnant adults, a dosage of 1-2 g IM or IV daily for 10-14 days has been suggested by CDC and others based on limited data.344,747
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
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 relapse.404 AAP recommends a duration of treatment of at least 7-10 days of treatment for uncomplicated disease.752 Immunocompromised patients may require longer duration of treatment as well as retreatment.752
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
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.1,3,18,30,32,148,151,152,154,155
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, AHA recommends that adults receive a single dose of 1 g given IM or IV 30-60 minutes prior to the procedure.451
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.1,3,18,30,32,73,77,84,85,104,105,107,170 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.1,3,18,30,32
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
Modification of the usual dosage of ceftriaxone is not usually necessary in adults with mild or moderate renal impairment alone who are receiving the drug in dosages up to 2 g daily.1,3,18,30,32,73,77,84,85,104,105,107,170 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.1,3,18,30,32
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.3,73,74,77,170
Ceftriaxone overdosage has been reported in patients with severe renal impairment.1,3,18,30,32 Reactions have included adverse neurological effects, including encephalopathy, seizures, myoclonus, and nonconvulsive status epilepticus.1,3,18,30,32,1,3,18,30,32 Adjust ceftriaxone dosage appropriately in patients with severe renal impairment.1,3,18,30,32
Because ceftriaxone is not removed by hemodialysis or peritoneal dialysis, supplemental doses of the drug are unnecessary during or after dialysis.1,1,3,18,30,32,73,77
Serious, occasionally fatal, hypersensitivity reactions (anaphylaxis or anaphylactoid) have been reported in patients receiving ceftriaxone.1,3,30,32
Other hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, bronchospasm, serum sickness, generalized exanthematous pustulosis, and severe cutaneous reactions (erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome/toxic epidermal necrolysis) also have been reported.1,3,30,32,92,120
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 allergies, particularly to drugs.1,18,30,32
When the Duplex® drug delivery system containing 1 or 2 g of ceftriaxone and 50 mL of 3.74 or 2.22% dextrose injection, respectively, is used, the possibility of hypersensitivity reactions to the dextrose component should be considered.3 Hypersensitivity reactions, including anaphylaxis, have been reported with dextrose-containing solutions;3 such reactions usually have been reported in patients receiving high dextrose concentrations (i.e., 50% dextrose), but also reported when corn-derived dextrose solutions were administered to patients with or without history of hypersensitivity to corn products.3
If a severe hypersensitivity reaction occurs, immediately discontinue the drug and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1,3,18,30,32
Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.3,170,184,325,432,433
Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, other β-lactam anti-infectives, or other drugs.1,3,18,30,32
Interaction with Calcium-containing Products
Fatalities have been reported in some neonates receiving ceftriaxone and calcium-containing IV solutions; a crystalline material was observed in the lungs and kidneys at autopsy.1,18,30,32 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.1,18,30,32 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.1,18,30,32,511
There have been no similar reports to date in patients other than neonates treated with ceftriaxone and calcium-containing IV solutions.1,3,18,30,32,507
There is some evidence that neonates have an increased risk for precipitation of ceftriaxone-calcium.1,3,18,30,32 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 with calcium concentrations ≥24 mg/dL in adult plasma or ≥16 mg/dL in neonatal plasma.1,3,18,30,32 This may reflect ceftriaxone-calcium precipitation.1,3,18,30,32
Ceftriaxone must not be admixed with calcium-containing IV solutions and must not be administered simultaneously with calcium-containing IV solutions, including calcium-containing infusions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age).1,3,18,30,32,507,529
There have been no reports to date of an interaction between ceftriaxone and oral calcium-containing products or between IM ceftriaxone and calcium-containing products (IV or oral).1,3,18,30,32,529
Serious adverse neurological reactions, including encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and nonconvulsive status epilepticus, have been reported during postmarketing surveillance of ceftriaxone use.1,3,18,30,32 These effects have been reversible upon discontinuance of the drug.1,3,18,30,32
In some cases, adverse neurological reactions occurred in patients with severe renal impairment who did not receive appropriate dosage adjustment of ceftriaxone.1,3,18,30,32 However, in other cases, such adverse reactions occurred in patients who did receive proper dosage adjustment.1,3,18,30,32
If adverse neurological reactions associated with ceftriaxone occur, discontinue the drug and initiate appropriate supportive treatment.1,3,18,30,32 Adjust ceftriaxone dosage appropriately in patients with severe renal impairment.1,3,18,30,32
Discontinue ceftriaxone if seizures occur; administer anticonvulsant therapy if clinically indicated.1,3,18,30,32
Superinfection/Clostridioides difficile-associated Diarrhea and Colitis
Use of ceftriaxone may result in overgrowth of nonsusceptible organisms,1,18,32,119,121,125,132,150,246,249,250,265 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. Careful observation of the patient during ceftriaxone therapy is essential.1,18,32 If superinfection or suprainfection occurs, appropriate therapy should be instituted.1,18,32
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile .1,3,18,30,32,302,303,304,305,328 C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis.1,3,18,30,32,303,304,305,328 C. difficile produces toxins A and B which contribute to the development of CDAD;1,3,18,30,32,303,304,305 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1,3,18,30,32
Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1,3,18,30,32 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1,3,18,30,32
If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible.1,3,18,30,32 Initiate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.1,3,18,30,32,529
Immune-mediated hemolytic anemia has been reported in patients receiving ceftriaxone.1,3,18,30,32 Severe cases of hemolytic anemia, including fatalities, have occurred in both adults and children.1,3,18,30,32,338,339,626 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
Consider the diagnosis of cephalosporin-associated anemia if anemia occurs in a patient receiving ceftriaxone.1,3,18,30,32 Discontinue the drug until the etiology of the anemia is determined.1,3,18,30,32
Selection and Use of Anti-infectives
To reduce the development of drug-resistant bacteria and maintain effectiveness of ceftriaxone and other antibacterials, ceftriaxone should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1,3,18,30,32 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1,3,18,30,32 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1,3,18,30,32
Prolonged prothrombin time (PT) has been reported rarely.1,3,18,30,32 Monitor PT in patients with impaired vitamin K synthesis or low vitamin K stores (e.g., chronic hepatic disease, malnutrition), and administer vitamin K when indicated.1,3,18,30,32 There is a possible increased risk of bleeding if ceftriaxone is used concomitantly with vitamin K antagonists.1,3,18,30,32
Ceftriaxone-calcium precipitates in the gallbladder have been reported rarely; symptoms of gallbladder disease (e.g., colic, nausea, vomiting, anorexia) can occur.1,3,18,30,32
The precipitates appear on sonography as an echo without acoustical shadowing (suggesting sludge) or as an echo with acoustical shadowing and may be misinterpreted as gallstones.1,3,18,30,32
The probability of gallbladder precipitates associated with ceftriaxone therapy appears to be greatest in pediatric patients.1,3,18,30,32
Discontinue ceftriaxone in patients with manifestations suggestive of gallbladder disease and/or if sonographic abnormalities characteristic of ceftriaxone-calcium precipitates are detected.1,3,18,30,32,248,256,308,309
The condition appears to be transient and generally resolves following discontinuance of the drug and conservative management.1,3,18,30,32,247,248,255,308 The time to resolution may range from a few days to several months.209,248,255,308,309
Consider upper abdominal ultrasonography 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
Urolithiasis and Post-renal Acute Renal Failure
Ceftriaxone-calcium precipitates in urine reported and may be detected as sonographic abnormalities.1,3,18,30,32 Patients may be asymptomatic or may develop symptoms of urolithiasis, ureteral obstruction, and post-renal acute renal failure.1,3,18,30,32
The probability of such precipitates appears to be greatest in pediatric patients.1,3,18,30,32
The condition appears to be reversible following discontinuance of the drug and conservative management.1,3,18,30,32
Ensure that patients are adequately hydrated during ceftriaxone therapy.1,3,18,30,32
Discontinue ceftriaxone in patients with signs and symptoms suggestive of urolithiasis, oliguria or renal failure, and/or if sonographic abnormalities characteristic of ceftriaxone-calcium precipitates are detected.1,3,18,30,32
Pancreatitis, possibly secondary to biliary obstruction, reported rarely.1,3,18,30 Most had preexisting risk factors for biliary stasis and biliary sludge (e.g., preceding major therapy, severe illness, total parenteral nutrition).1,3,18,30
Co-factor role of ceftriaxone-related biliary precipitation cannot be ruled out.1,3,18,30
The Duplex® drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection, respectively, should be used with caution in patients with overt or known subclinical diabetes mellitus and in patients with carbohydrate intolerance.3
Although IM injections of ceftriaxone can be prepared using 1% lidocaine hydrochloride, consider all contraindications to lidocaine before administering such injections.1 IV administration of ceftriaxone solutions containing lidocaine is contraindicated.1,18,32
Commercially available preparations of ceftriaxone contain approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone.1,3,18,30,30,32
Reproduction studies in mice, rats, and primates have not revealed any evidence of embryotoxicity, fetotoxicity, or teratogenicity with ceftriaxone.1,3,18,30,32
Available data from published prospective cohort studies, case series, and case reports over several decades with use of cephalosporins, including ceftriaxone, in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.3 Ceftriaxone crosses the placenta.3
No adequate or controlled studies with ceftriaxone have been conducted in pregnant women.1,18,30,32 Use ceftriaxone during pregnancy only when clearly needed.1,18,30,32
Ceftriaxone is distributed into milk in low concentrations; use the drug with caution in breast-feeding women.1,3,30,32 The effects of ceftriaxone on nursing infants or on milk production are not known.3 Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ceftriaxone and any potential adverse effects on the infant from the drug or the mother's underlying condition.3
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).1,18,32
Ceftriaxone is also contraindicated in hyperbilirubinemic neonates, particularly those who are premature.1,18,30,32 Ceftriaxone can displace bilirubin from albumin binding sites in vitro.1,18,30,32,237,238 Therefore, there is a possible risk of bilirubin encephalopathy if the drug is used in hyperbilirubinemic neonates.1,18,30,32,507
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.1,18,30,32,529 Fatalities associated with ceftriaxone-calcium precipitates in lungs and kidneys have been reported in neonates who received ceftriaxone and calcium-containing IV solutions.1,18,30,32,507
To reduce the risk of bilirubin encephalopathy, IV infusions of ceftriaxone should be given over 60 minutes in neonates.1,18,32
Do not use ceftriaxone IM injections prepared using bacteriostatic water for injection containing benzyl alcohol in neonates176,177 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
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.1,3,18,30,32 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.1,3,18,30,32
The pharmacokinetics of ceftriaxone are only minimally altered in geriatric patients compared with healthy younger adults.1,3,18,30,32 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.1,3,18,30,32
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
Hepatic impairment generally does not affect ceftriaxone pharmacokinetics; dosage adjustments not usually needed unless both hepatic and renal function are impaired.1
In those with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed a dosage of 2 g daily.1,3,18,30 Some manufacturers and clinicians suggest monitoring serum ceftriaxone concentrations periodically and adjusting dosage if there is evidence of accumulation.3,73,74,77,170
Since ceftriaxone is eliminated by both biliary and renal routes, dosage adjustments not usually needed in patients with mild to moderate renal impairment alone.1,73,74,77,170,84,85,104,105,107,170
In those with clinically significant renal disease and hepatic impairment, use caution and do not exceed a dosage of 2 g daily.1,3,18,30 Some clinicians suggest monitoring serum ceftriaxone concentrations periodically in patients with severe renal impairment (e.g., dialysis patients) or with both renal and hepatic impairment; adjust dosage if there is evidence of accumulation.3,18,73,74,77,170
Ceftriaxone overdosage has been reported in patients with severe renal impairment.1,3,18,30,32 Reactions have included adverse neurological effects, including encephalopathy, seizures, myoclonus, and nonconvulsive status epilepticus.1,3,18,30,32 Adjust ceftriaxone dosage appropriately in patients with severe renal impairment.1,3,18,30,32
Common adverse effects include local reactions at the administration site (warmth, tightness, induration, phlebitis), hematologic effects (eosinophilia, thrombocytosis, leukopenia), and hypersensitivity reactions.1
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
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
Concomitant use of ceftriaxone and vitamin K antagonists may increase the risk of bleeding.1,18,30,32 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.1,18,30,32
Antagonism has been reported in vitro when ceftriaxone was used in combination with chloramphenicol.1,3,18,30,32
Concomitant administration of oral probenecid (500 mg daily) does not appear to affect the pharmacokinetics of ceftriaxone,1,3,18,30,32,84,104,170,179 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
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
Interference with Glucose Measurements
False-positive results for urinary glucose may occur in patients receiving ceftriaxone if nonenzymatic glucose test methods are used.1,18,32 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.1,18,32
The presence of ceftriaxone may result in falsely low estimated blood glucose concentrations measured using some blood glucose monitoring systems.1,18,32 The manufacturer's instructions for the glucose monitoring system should be consulted and alternative testing methods should be used if necessary.1,18,32
Ceftriaxone is classified as a third generation cephalosporin based on its spectrum of activity.104,105,106,108,162,165,170 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 cephalosporins,4,7,23,36,37,104,105,106,170 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 Ceftriaxone usually is bactericidal in action.1,3,4,18,22,30,32,41,104 Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall.1,3,18,30,32,104
Ceftriaxone is active in vitro against many gram-positive aerobic, many gram-negative aerobic bacteria, and some anaerobic bacteria; the drug is inactive against Chlamydia , fungi, and viruses.1 The drug is active in vitro and in clinical infections against Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci; GAS), Staphylococcus aureus (including penicillinase-producing strains), S. epidermidis , and viridans streptococci .1,7,14,22,23,36,37,45,104,106,108,121,123 Ceftriaxone also is active in vitro against S. agalactiae (group B streptococci; GBS).1,7,9,14,22,23,43,45,104,106,128 Methicillin-resistant (oxacillin-resistant) staphylococci and most enterococci (e.g., Enterococcus faecalis ) are resistant to the drug.1,6,7,14,16,22,23,36,37,39,45,46,104,106,120 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.166 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 Resistance to ceftriaxone has been reported in some environmental isolates of N. asteroides ,527 and clinical isolates of N. farcinica .701 Ceftriaxone is active in vitro and in clinical infections against Acinetobacter calcoaceticus ,1 Enterobacter (including E. aerogenes ,1 E. cloacae ),1 Escherichia coli , Haemophilus influenzae (including ampicillin-resistant and β-lactamase-producing strains),1 H. parainfluenzae ,1 Klebsiella pneumoniae ,1 K. oxytoca ,1 Moraxella catarrhalis (including β-lactamase-producing strains),1 Morganella morganii ,1 Neisseria gonorrhoeae ,1 N. meningitidis ,1 Proteus mirabilis ,1 P. vulgaris ,1 Pseudomonas aeruginosa ,1 and Serratia marcescens .1 The drug also is active in vitro against Bartonella ,354 Capnocytophaga ,461,462 Citrobacter ,1 Providencia ,1 Salmonella ,14,17,37,40 and Shigella .1,4,14,36,37,106 Ceftriaxone is less active than ceftazidime against Ps. aeruginosa .10,101,106 Ceftriaxone is active in vitro and in clinical infections against Clostridium (except Clostridioides difficile )1,16,19,22,23,36 and Peptostreptococcus .1,7,8,16,19,22 The drug also is active in vitro against Prevotella ,1 and Porphyromonas melaninogenicus .1 Most strains of Bacteroides fragilis are resistant to ceftriaxone.6,7,8,14,16,19,22,36 The drug has some activity against Treponema pallidum when tested in a rabbit model.173 Ceftriaxone is active in vitro against Borrelia burgdorferi , the causative agent of Lyme disease.207,283,284,285,340,341 The drug also is active in vitro against Leptospira , including L. interrogans and L. weilii .696
Ceftriaxone is not appreciably absorbed from the GI tract and must be given parenterally.170 The drug appears to be completely absorbed following IM administration in healthy adults;1,52,57,84 peak serum concentrations are attained 1.5-4 hours after the dose.1,48,52,57 Multiple-dose studies in healthy adults indicate that serum concentrations at steady state on day 4 of therapy are 15-36% higher than serum concentrations attained with single doses.1,56,84,170 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. 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 CSF concentrations are higher in patients with inflamed meninges.65,84,104 Ceftriaxone crosses the placenta and is distributed into amniotic fluid.66,84,104 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 Ceftriaxone binds mainly to albumin.84,104,170 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 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 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 is excreted both by renal and nonrenal mechanisms.1,72,84,104,170 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 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 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 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
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
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 for Injection, for IV Infusion (available in dual-chambered Duplex® drug delivery system with 3.74% dextrose injection) | ||||
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 | |||
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
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
Only references cited for selected revisions after 1984 are available electronically.
1. Hospira, Inc. Ceftriaxone sodium injection powder, for solution prescribing information. Lake Forest, IL; 2022 Mar.
3. B Braun Medical Inc. Ceftriaxone for injection and dextrose injection in Duplex® container, for intravenous use prescribing information. Bethlehem, PA; 2022 Jan.
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]
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. [PubMed 6969574]
8. Rolfe RD, Finegold SM. Comparative in vitro activity of ceftriaxone against anaerobic bacteria. Antimicrob Agents Chemother . 1982; 22:338-41. [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]
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]
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. [PubMed 6372681]
18. Hospira, Inc. Ceftriaxone sodium for injection (pharmacy bulk package) prescribing information. Lake Forest, IL; 2022 Mar.
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. [PubMed 6307137]
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. [PubMed 7114839]
30. Baxter Healthcare Corporation. Ceftriaxone sodium injection, iso-osmotic solution in dextrose prescribing information. Deerfield, IL; 2024 Mar.
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