VA Class:AM117

AHFS Class:

• Third Generation Cephalosporins 8:12.06.12

Generic Name(s):

• Cefotaxime Sodium

Associated Monographs

• Cephalosporins General Statement

Cefotaxime is a semisynthetic, third generation cephalosporin antibiotic.

Cefotaxime is used for the treatment of serious bone and joint infections, serious intra-abdominal and gynecologic infections (including peritonitis, endometritis, pelvic inflammatory disease, pelvic cellulitis), meningitis and other CNS infections, serious lower respiratory tract infections (including pneumonia), bacteremia/septicemia, serious skin and skin structure infections, and serious urinary tract infections caused by susceptible bacteria.230 The drug also is used in the treatment of gonorrhea,167,230,275 typhoid fever and other infections caused by Salmonella †,197,275,304,305,306,307,308 infections caused by Vibrio parahaemolyticus †218 or V. vulnificus †,197,250 and Lyme disease†.197,275,284,285,351 Cefotaxime also has been used for perioperative prophylaxis.169,230

Prior to initiation of cefotaxime therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests. If cefotaxime therapy is started pending results of susceptibility tests, it should be discontinued if the causative organism is found to be resistant to the drug. Because resistant strains of some organisms, especially Enterobacter, Ps. aeruginosa , and Serratia , have developed during cefotaxime therapy, it is important that appropriate specimens be obtained periodically until the infection is eradicated and cefotaxime is discontinued. In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in the empiric treatment of other serious infections when the causative organism has not been identified, cefotaxime may be used concomitantly with an aminoglycoside pending results of in vitro susceptibility tests. In infections which fail to respond to cefotaxime although in vitro tests indicate that the causative organism is susceptible to the drug, the presence of undrained abscesses or vascular infections should be suspected. The possibility that the organism may be tolerant to cefotaxime should also be considered. (See Resistance.) Use of cefotaxime does not replace surgical procedures such as incision and drainage when indicated.

Gram-positive Aerobic Bacterial Infections

Cefotaxime is used in the treatment of lower respiratory tract infections caused by susceptible Streptococcus pneumoniae , S. pyogenes (group A β-hemolytic streptococci), other streptococci (except enterococci), or Staphylococcus aureus (penicillinase-producing and nonpenicillinase-producing strains); genitourinary tract infections caused by susceptible S. aureus , S. epidermidis , or enterococci; gynecologic infections caused by susceptible S. epidermidis or streptococci (including enterococci); skin and skin structure infections caused by susceptible S. aureus , S. epidermidis , group A β-hemolytic streptococci, or other streptococci (including enterococci); intra-abdominal infections caused by susceptible streptococci; or bone and joint infections caused by susceptible S. aureus , group A β-hemolytic streptococci, or other streptococci. Cefotaxime generally should not be used in the treatment of infections caused by gram-positive bacteria when a penicillin or a first generation cephalosporin could be used. Although cefotaxime has been effective in the treatment of cellulitis, wound infections, septicemia, and lower respiratory tract infections caused by susceptible staphylococci or streptococci, treatment failures have been reported when the drug was used in the treatment of osteomyelitis caused by S. aureus.

Gram-negative Aerobic Bacterial Infections

Cefotaxime is used in the treatment of lower respiratory tract infections caused by susceptible Escherichia coli , Klebsiella , Haemophilus influenzae (including ampicillin-resistant strains), H. parainfluenzae , Proteus mirabilis , indole-positive Proteus , Serratia marcescens , or Enterobacter ; genitourinary tract infections caused by susceptible Citrobacter , Enterobacter , E. coli , Klebsiella , P. mirabilis , Providencia stuartii (formerly group B Proteus inconstans ), Pseudomonas , Morganella morganii , Providencia rettgeri , P. vulgaris , S. marcescens , or Neisseria gonorrhoeae ; intra-abdominal and gynecologic infections caused by susceptible E. coli , Enterobacter , Klebsiella , or P. mirabilis ; bacteremia or septicemia caused by susceptible E. coli , Klebsiella , or S. marcescens ; skin and skin structure infections caused by susceptible E. coli , Enterobacter , Klebsiella , P. mirabilis , M. morganii , P. rettgeri , P. vulgaris , Pseudomonas , or S. marcescens ; or bone and joint infections caused by susceptible P. mirabilis .

It has been suggested that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) may be drugs of choice for the treatment of many infections caused by susceptible Enterobacteriaceae, including susceptible E. coli , K. pneumoniae , P. rettgeri , M. morganii , P. vulgaris , P. stuartii , or Serratia ;197,290,301 an aminoglycoside (amikacin, gentamicin, tobramycin) usually is used concomitantly in severe infections.197

Although cefotaxime has been effective when used in the treatment of infections caused by susceptible Ps. aeruginosa , other anti-infectives generally are preferred for the treatment of pseudomonal infections.197 Because most strains of Ps. aeruginosa require high concentrations of the drug for in vitro inhibition and resistant strains have developed during cefotaxime therapy, an aminoglycoside should be used concomitantly if cefotaxime is used in any infection where Ps. aeruginosa may be present.

Anaerobic and Mixed Aerobic-Anaerobic Bacterial Infections

Cefotaxime has been used in the treatment of skin and skin structure infections, intra-abdominal infections, or gynecologic infections caused by susceptible Bacteroides (including B. fragilis ), Clostridium , Fusobacterium (including F. nucleatum ), or anaerobic gram-positive cocci (including Peptococcus and Peptostreptococcus );230 however, cefotaxime is not considered a drug of choice for these infections.197 Cefotaxime has been effective when used in the treatment of mixed aerobic-anaerobic infections, including intra-abdominal and gynecologic infections (see Uses: Pelvic Inflammatory Disease).230,290 Because many strains of B. fragilis are resistant to cefotaxime, some clinicians recommend that cefotaxime not be used alone for the treatment of serious intra-abdominal infections when B. fragilis may be present.310,311

Meningitis and Other CNS Infections

Cefotaxime is used in neonates, children, or adults for the treatment of meningitis and ventriculitis caused by susceptible H. influenzae , N. meningitidis , or S. pneumoniae .230,291,294,296,335,365 The drug also has been used for the treatment of meningitis and other CNS infections caused by susceptible Enterobacteriaceae† (e.g., Escherichia coli , Klebsiella pneumoniae ).230,291,294,296,336,365 Cefotaxime is ineffective in and should not be used alone for empiric treatment of meningitis when Listeria monocytogenes , enterococci, staphylococci, or Pseudomonas aeruginosa may be involved.290,296,319

Empiric Treatment of Meningitis

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.275,282,296,297,318,323,365 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.281,282,296,318,365 There is some evidence that short-term adjunctive therapy with IV dexamethasone may decrease the incidence of audiologic and/or neurologic sequelae in infants and children with H. influenzae meningitis and possibly may provide some benefit in patients with S. pneumoniae meningitis.275,282,296,318,324,365 The American Academy of Pediatrics (AAP) and other clinicians suggest that use of adjunctive dexamethasone therapy may be considered during the initial 2-4 days of anti-infective therapy in infants and children 6-8 weeks of age or older with known or suspected bacterial meningitis, especially in those with suspected or proven H. influenzae infection.275,282,296,318,320,323,365 If used, dexamethasone should be initiated before or concurrently with the first dose of anti-infective.275,365 (See Uses: Bacterial Meningitis in the Corticosteroids General Statement 68:04 and see Dexamethasone 68:04.)

Bacterial meningitis in neonates usually is caused by S. agalactiae (group B streptococci), L. monocytogenes , or aerobic gram-negative bacilli (e.g., E. coli , K. pneumoniae ).197,275,281,282,296,318,319,323,365 The AAP and other clinicians recommend that neonates 4 weeks of age or younger with suspected bacterial meningitis receive an empiric regimen of IV ampicillin and an aminoglycoside pending results of CSF culture and susceptibility testing.275,365 Alternatively, neonates can receive an empiric regimen of IV ampicillin and IV cefotaxime or IV ceftazidime (with or without gentamicin).197,275,281,282,296,318,319,323,365 Because frequent use of cephalosporins in neonatal units may result in rapid emergence of resistant strains of some gram-negative bacilli (e.g., Enterobacter cloacae , Klebsiella , Serratia ), the AAP cautions that cephalosporins should be used for empiric treatment of meningitis in neonates only if gram-negative bacterial meningitis is strongly suspected.275 Consideration should be given to including IV vancomycin in the initial empiric regimen if S. pneumoniae , enterococci, or staphylococci is suspected.275,297,347 Because ceftriaxone should be used with caution in neonates who are hyperbilirubinemic (especially those born prematurely), cefotaxime may be the preferred cephalosporin in neonates.275,282 Alternatively, because premature, low-birthweight neonates are at increased risk for nosocomial infection caused by staphylococci or gram-negative bacilli, some clinicians suggest that these neonates receive an empiric regimen of IV ceftazidime and IV vancomycin.296

In infants beyond the neonatal stage who are younger than 3 months of age, bacterial meningitis may be caused by S. agalactiae , L. monocytogenes , Haemophilus influenzae , S. pneumoniae , N. meningitidis , or aerobic gram-negative bacilli (e.g., E. coli , K. pneumoniae ).275,281,282,296,318,319,323,365 An empiric regimen recommended for infants in this age group is IV ampicillin and either IV cefotaxime or IV ceftriaxone.275,281,282,296,318,319,323 Because of the increased prevalence of S. pneumoniae resistant to penicillin, cefotaxime, and ceftriaxone, the initial empiric regimen in children 1 month of age or older should include vancomycin and either cefotaxime or ceftriaxone if meningitis is known or suspected to be caused by S. pneumoniae .275,297,365

In children 3 months through 17 years of age, bacterial meningitis usually is caused by N. meningitidis , S. pneumoniae , or H. influenzae , and the most common cause of bacterial meningitis in adults 18-50 years of age is N. meningitidis or S. pneumoniae .197,275,282,296,318,323,365 Most clinicians recommend that children 3 months through 17 years of age and adults 18-50 years of age receive IV cefotaxime or IV ceftriaxone for empiric therapy of suspected bacterial meningitis;197,275,282,296,318,319,323,365 an alternative regimen in children 3 months through 17 years of age is IV ampicillin and IV chloramphenicol.282,318 In addition, because of the increasing incidence of penicillin-resistant S. pneumoniae with reduced susceptibility to cephalosporins, the AAP and others suggest that the initial empiric regimen include IV vancomycin (with or without rifampin) pending results of in vitro susceptibility tests;197,275,281,297,320,323,328,365 vancomycin and rifampin should be discontinued if the causative organism is found to be susceptible to cephalosporins.197,297,325 .328 The US Centers for Disease Control and Prevention (CDC) and some clinicians have recommended that vancomycin be added to the empiric regimen in areas where there have been reports of highly penicillin-resistant strains of S. pneumoniae ,197,275,276,277,280,330,333,334 but other clinicians suggest that use of cefotaxime or ceftriaxone in conjunction with vancomycin provides the optimal initial empiric regimen.323,325 While L. monocytogenes meningitis is relatively rare in this age group, the empiric regimen should include ampicillin if L. monocytogenes is suspected.318,319

In adults older than 50 years of age, bacterial meningitis usually is caused by S. pneumoniae , L. monocytogenes , N. meningitidis , or aerobic gram-negative bacilli, and the empiric regimen recommended for this age group is IV ampicillin given in conjunction with IV cefotaxime or IV ceftriaxone.296,318,319,365 If S. pneumoniae is suspected, the empiric regimen also should include IV vancomycin (with or without rifampin); vancomycin and rifampin should be discontinued if the causative organism is found to be susceptible to the cephalosporin. 197,296,320,365

Meningitis Caused by Streptococcus pneumoniae

IV cefotaxime and IV ceftriaxone are considered drugs of choice for the treatment of meningitis caused by S. pneumoniae .275,297,318,365 While cefotaxime and ceftriaxone generally have been considered the drugs of choice for the treatment of meningitis caused by penicillin-resistant S. pneumoniae , treatment failures have been reported when the drugs were used alone for the treatment of meningitis caused by strains of S. pneumoniae with intermediate or high-level penicillin resistance (i.e., penicillin MIC 0.1 mcg/mL or greater).275,277,283,329,331,332,333,334 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.275,320,322,323 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 regimens and initial therapy for serious pneumococcal infections.275,276,280,320,334 Because susceptibility can no longer be assumed, S. pneumoniae isolates should be routinely tested for in vitro susceptibility.275,276,277,282,297,330

If anti-infective therapy in a patient with meningitis is initiated with an empiric regimen of IV cefotaxime 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 cefotaxime and susceptible or resistant to penicillin, vancomycin can be discontinued and therapy completed using cefotaxime alone.275,297 If the isolate is found to have reduced susceptibility to cefotaxime and penicillin, both IV cefotaxime and IV vancomycin (with or without rifampin) usually are continued.275,318,319 If the patient's condition does not improve or worsens or results of a second repeat lumber puncture (performed 24-36 hours after initiation of anti-infective therapy) indicate that the anti-infective regimen has not eradicated or reduced the number of pneumococci in CSF, rifampin probably should be added to the regimen or vancomycin discontinued and replaced with rifampin.275,297 If meningitis is caused by S. pneumoniae highly resistant to cefotaxime (i.e., MIC 2-4 mcg/mL or greater), consultation with an infectious disease expert is recommended.275,297

Meningitis Caused by Haemophilus influenzae

IV cefotaxime and IV ceftriaxone are considered drugs of choice for the treatment of meningitis caused by susceptible H. influenzae (including penicillinase-producing strains).197,275,282,296,318,365 The AAP suggests that children with meningitis possibly caused by H. influenzae receive an initial treatment regimen of cefotaxime, ceftriaxone, or a regimen of ampicillin given in conjunction with chloramphenicol;275 some clinicians prefer cefotaxime or ceftriaxone for the initial treatment of meningitis caused by H. influenzae 197,318 since the drugs are active against both β-lactamase-producing and non-β-lactamase-producing strains.318 The incidence of H. influenzae meningitis in the US has decreased considerably since H. influenzae type b conjugate vaccines became available for immunization of infants.275,319,323

Meningitis Caused by Neisseria meningitidis

Although IV penicillin G or ampicillin generally are considered the drugs of choice for the treatment of meningitis caused by N. meningitidis , IV cefotaxime and IV ceftriaxone are acceptable alternatives.197,275,296,318,323,365

Meningitis Caused by Enterobacteriaceae

Some clinicians recommend that meningitis caused by Enterobacteriaceae (e.g., E. coli , K. pneumoniae ) be treated with a third generation cephalosporins (i.e., cefotaxime, ceftazidime, ceftriaxone) with or without an aminoglycoside.282,318,365 Because ceftazidime or cefepime (but not cefotaxime or ceftriaxone) is effective for the treatment of meningitis caused by Ps. aeruginosa , some clinicians suggest that a regimen of ceftazidime or cefepime (with or without an aminoglycoside) may be preferred for the treatment of meningitis caused by gram-negative bacilli pending results of culture and susceptibility testing.296,318,365

Brain Abscess and Other CNS Infections

IV cefotaxime has been effective when used in conjunction with metronidazole for empiric treatment of brain abscess in patients 6 months of age or older.336,347 Bacterial brain abscesses and other CNS infections (e.g., subdural empyema, intracranial epidural abscesses) often are polymicrobial and can be caused by gram-positive aerobic cocci, Enterobacteriaceae (e.g., E. coli , Haemophilus , Klebsiella ), and/or anaerobic bacteria (e.g., Bacteroides , Fusobacterium ).319,336,347

The choice of anti-infectives for empiric therapy of these infections should be based on the predisposing condition and site of primary infection.319,347 Some clinicians suggest that the empiric anti-infective regimen in patients who develop the CNS infections after respiratory tract infection (e.g., otitis media, mastoiditis, paranasal sinusitis, pyogenic lung disease) should consist of an appropriate IV third generation cephalosporin (e.g., cefotaxime) given in conjunction with metronidazole, employing the cephalosporin rather than a penicillin to extend coverage to Haemophilus and facultative anaerobic gram-negative bacteria; if presence of staphylococci is suspected, a penicillinase-resistant penicillin (e.g., nafcillin, oxacillin) or vancomycin should be added to the empiric regimen.319,347 In patients who develop brain abscess, subdural empyema, or intracranial epidural abscess after trauma or neurosurgery, the empiric regimen should consist of an appropriate IV third generation cephalosporin (e.g., cefotaxime) given in conjunction with a penicillinase-resistant penicillin or vancomycin.319,347 Prolonged anti-infective therapy (e.g., 3-6 weeks or longer) usually is required for these CNS infections.319,347

Gonorrhea and Associated Infections

Gonococcal Infections in Adults and Adolescents

Uncomplicated Gonorrhea

Cefotaxime has been used for the treatment of uncomplicated cervical, urethral, or rectal gonorrhea caused by susceptible Neisseria gonorrhoeae , including penicillinase-producing N. gonorrhoeae (PPNG) in adults and adolescents.167,230,275,366,367

For the treatment of uncomplicated urogenital, anorectal, or pharyngeal gonorrhea, the CDC states that a combination regimen that includes a single 250-mg IM dose of ceftriaxone and either oral azithromycin (single 1-g dose) or oral doxycycline (100 mg twice daily for 7 days) is the regimen of choice.166 Although a single 500-mg dose of IM cefotaxime may be effective for the treatment of uncomplicated urogenital and anorectal gonorrhea, the CDC states that the drug does not offer any advantages over IM ceftriaxone for urogenital infections and its efficacy for pharyngeal infections is less certain.167

Disseminated Gonococcal Infections

IV cefotaxime has been used for initial treatment of disseminated gonococcal infections† in adults and adolescents.167

The CDC recommends that treatment of disseminated gonococcal infections in adults and adolescents be initiated with a multiple-dose regimen of IM or IV ceftriaxone;167 a multiple-dose regimen of IV cefotaxime is considered an alternative.167 The initial parenteral regimen should be continued for 24-48 hours after improvement begins; therapy can then be switched to oral cefixime and continued to complete at least 1 week of treatment.167

The CDC recommends that the patient be hospitalized for initial treatment, especially when compliance may be a problem, when the diagnosis is uncertain, or when the patient has purulent synovial effusions or other complications.167 Patients should be examined for clinical evidence of endocarditis and meningitis; the recommended regimen for these infections is IV ceftriaxone.167

Gonococcal Infections in Neonates and Infants

Cefotaxime is used for the treatment of N. gonorrhoeae infections in neonates, including disseminated gonococcal infections and gonococcal scalp abscesses†.167,275 The CDC states that IV or IM ceftriaxone or IV or IM cefotaxime are the drugs of choice for these infections in neonates;167,275 the AAP states that cefotaxime is preferred in neonates with hyperbilirubinemia.275 IV or IM ceftriaxone is the drug of choice for the treatment of nondisseminated gonococcal infections in neonates, including gonococcal ophthalmia (ophthalmia neonatorum), and also is the drug of choice for disseminated gonococcal infections (e.g., sepsis, arthritis, meningitis) in children.167,275

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.167 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 inflammation at sites of fetal monitoring (e.g., scalp).167 Because a neonate with gonococcal infection usually has acquired the organism from its mother, both the mother and her sexual partner(s) should be evaluated and treated for gonorrhea.167,275

While universal topical prophylaxis using 0.5% erythromycin ophthalmic ointment, silver nitrate 1% topical solution (no longer commercially available in the US), or 1% tetracycline ophthalmic ointment (no longer commercially available in the US) is recommended for all neonates as soon as possible after birth to prevent gonococcal ophthalmia neonatorum, these topical anti-infectives are inadequate for prophylaxis of gonococcal infections at other sites, and may be ineffective in preventing chlamydial ocular infections.167,275 Because neonates born to mothers with untreated gonorrhea are at high risk of infection with N. gonorrhoeae , the CDC and AAP recommend that, in addition to topical prophylaxis , these neonates should receive parenteral prophylaxis against the disease.167,275 The CDC and AAP currently recommend that neonates born to mothers with documented peripartum gonococcal infection receive parenteral prophylaxis with a single IM or IV dose of ceftriaxone (25-50 mg/kg not to exceed 125 mg).167,275

For additional information on current recommendations for the treatment of gonorrhea and associated infections, see Uses: Gonorrhea and Associated Infections, in Ceftriaxone 8:12.06.12.

GI Infections

Cefotaxime is used for empiric treatment of infectious diarrhea†.412 For empiric treatment of severe diarrhea in HIV-infected individuals, the CDC, National Institutes of Health (NIH), and Infectious Diseases Society of America (IDSA) state that ciprofloxacin is the drug of choice and ceftriaxone and cefotaxime are reasonable alternatives.412 (For information on Salmonella gastroenteritis, see Salmonella Gastroenteritis under Uses: Typhoid Fever and Other Salmonella Infections.)

Yersinia Infections

Although GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis usually are self-limited and anti-infective therapy unnecessary, the AAP, IDSA, and others recommend use of anti-infectives in immunocompromised individuals or for the treatment of severe infections or when septicemia or other invasive disease occurs.218,245,275 GI infections caused by Y. enterocolitica or Y. pseudotuberculosis can occur as the result of ingesting undercooked pork, unpasteurized milk, or contaminated water; infection has occurred in infants whose caregivers handled contaminated chitterlings (raw pork intestines) or tofu.218 Use of co-trimoxazole, an aminoglycoside (e.g., amikacin, gentamicin, tobramycin), a fluoroquinolone (e.g., ciprofloxacin), doxycycline, or cefotaxime has been recommended when treatment is considered necessary;197,218,245 combination therapy may be necessary.245 Some clinicians suggest that, while cefotaxime may be effective in the treatment of Y. enterocolitica bacteremia,268 the role of anti-infectives, including oral anti-infectives, in the management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.268,275

Lyme Disease

Cefotaxime is used in the treatment of Lyme disease†.197,273,275,351,354 The IDSA and other clinicians recommend IV cefotaxime as a preferred alternative to IV ceftriaxone for the treatment of early neurologic Lyme disease† with acute neurologic manifestations such as meningitis or radiculopathy, Lyme carditis†, Lyme arthritis†, and late neurologic Lyme disease†.273,275,351,354

Lyme disease is a tick-borne spirochetal disease.267,273,274,338,340 In the US, Lyme disease is caused by the spirochete Borrelia burgdorferi , which is transmitted by the bite of Ixodes scapularis or I. pacificus ticks.267,273,274,338,340 For additional information on Lyme disease, see Lyme Disease in Uses: Spirochetal Infections, in the Tetracyclines General Statement 8:12.24.

Early Lyme Disease

Early Neurologic Lyme Disease

Although oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil) generally are effective for the treatment of the early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations or advanced atrioventricular (AV) heart block,270,273,275,284,285,286,287,338,351,353,355,356,357 parenteral anti-infectives are recommended for the treatment of early Lyme disease when there are acute neurologic manifestations such as meningitis or radiculoneuritis.270,273,275,284,285,286,287,338,351,353,355,356

The IDSA and other clinicians recommend a 14-day regimen (range: 10-28 days) of IV ceftriaxone as the preferred parenteral regimen for the treatment of acute neurologic Lyme disease manifested by meningitis or radiculopathy; IV cefotaxime and IV penicillin G sodium are the preferred alternatives.351,354 In patients with acute neurologic manifestations who are intolerant of cephalosporins and penicillin, there is some evidence that oral doxycycline may be an adequate alternative that can be considered for use in adults and children 8 years of age or older.351

Although IV cefotaxime appears to be as effective as IV ceftriaxone for the treatment of acute neurologic Lyme disease and does not cause the biliary complications reported with ceftriaxone,351,368 ceftriaxone has the advantage of once-daily dosing.351 Limited data suggest that IV cefotaxime (6 g daily in divided doses for 10 days) is at least as effective as IV penicillin G (20 million units daily for 10 days) in patients with late complications of Lyme disease (e.g., severe radiculitis and/or meningitis, peripheral neuropathy, arthritis).266,267

Lyme Carditis

Cefotaxime is used as an alternative to ceftriaxone when a parenteral regimen is indicated for the treatment of Lyme carditis†.273,275,351,354 The IDSA states that patients with AV heart block and/or myopericarditis associated with early Lyme disease may be treated with a 14-day regimen (range: 14-21 days) of oral or parenteral anti-infectives.351 Although there is no evidence to date to suggest that a parenteral regimen is more effective than an oral regimen for the treatment of Lyme carditis, a parenteral regimen usually is recommended for initial treatment of hospitalized patients; an oral regimen can be used to complete therapy and for the treatment of outpatients.273,275,351,354 When a parenteral regimen is used, IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium is recommended.273,275,351,354 When an oral regimen is used, oral doxycycline, oral amoxicillin, or oral cefuroxime axetil is recommended.273,275,351,354

Because of the potential for life-threatening complications, hospitalization and continuous monitoring is advisable for patients who are symptomatic (syncope, dyspnea, chest pain) and also is recommended for those with second- or third-degree AV block or first-degree heart block when the PR interval is prolonged to 0.3 seconds or longer.351,354 Patients with advanced heart block may require a temporary pacemaker and consultation with a cardiologist is recommended.273,351,354

Late Lyme Disease

Lyme Arthritis

Cefotaxime is used as an alternative to ceftriaxone when a parenteral regimen is indicated for the treatment of Lyme arthritis†.273,275,351,354,361 While patients with uncomplicated Lyme arthritis without clinical evidence of neurologic disease generally can be treated with a 28-day regimen of oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil),273,351,354,361 the IDSA and other clinicians state that patients with Lyme arthritis and concomitant neurologic disease should receive a 14-day parenteral regimen (range: 14-28 days) of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G.273,275,351,354,361 While oral regimens are easier to administer, associated with fewer serious adverse effects, and less expensive than IV regimens, some patients with Lyme arthritis treated with oral anti-infectives have subsequently developed overt neuroborreliosis, which may require IV therapy for successful resolution.351 Therefore, additional study is needed to fully evaluate the comparative safety and efficacy of oral versus IV anti-infectives for the treatment of Lyme arthritis.351

In patients who have persistent or recurrent joint swelling after a recommended oral regimen, the IDSA and other clinicians recommend retreatment with the oral regimen or a switch to a parenteral regimen.273,351,354 Some clinicians prefer retreatment with an oral regimen for patients whose arthritis substantively improved but did not completely resolve; these clinicians reserve parenteral regimens for those patients whose arthritis failed to improve or worsened.351 It has been suggested that clinicians should consider allowing several months for joint inflammation to resolve after initial treatment before an additional course of anti-infectives is given.351

Late Neurologic Lyme Disease

Cefotaxime is used as an alternative to ceftriaxone for the treatment of late neurologic Lyme disease†.351 The IDSA and other clinicians state that patients with late neurologic Lyme disease affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy) should receive a 14-day regimen (range: 14-28 days) of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium.351 Response to anti-infective treatment usually is slow and may be incomplete in patients with late neurologic Lyme disease.351 The IDSA states that retreatment is not recommended unless relapse is shown by reliable objective measures.351

Pelvic Inflammatory Disease

Cefotaxime has been used for the treatment of pelvic inflammatory disease (PID).167,263,290,298,299 Because cefotaxime (like other cephalosporins) has no activity against Chlamydia trachomatis , it should be given in conjunction with an anti-infective active against this organism (e.g., doxycycline) whenever it is used in the treatment of PID.230,290

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.167,299 PID generally is a polymicrobial infection most frequently caused by N. gonorrhoeae and/or Chlamydia trachomatis ; however, organisms that are part of the normal vaginal flora (e.g., anaerobic bacteria, Gardnerella vaginalis , H. influenzae , enteric gram-negative bacilli, S. agalactiae ) or mycoplasma (e.g., Mycoplasma hominis , Ureaplasma urealyticum ) also may be involved.167,298,299 PID is treated with an empiric regimen that provides broad-spectrum coverage.167,298,300 The regimen should be effective against N. gonorrhoeae and C. trachomatis and also probably should be effective against anaerobes, gram-negative facultative bacteria, and streptococci.167,299,300 The optimum empiric regimen for the treatment of PID has not been identified.167 A wide variety of parenteral and oral regimens have been shown to achieve clinical and microbiologic cure in randomized studies with short-term follow-up;167,298,300 however, only limited data are available to date regarding elimination of infection in the endometrium and fallopian tubes or intermediate or long-term outcomes, including the impact of these regimens on the incidence of long-term sequelae of PID (e.g., tubal infertility, ectopic pregnancy, pain).167,300

When a parenteral regimen is indicated for the treatment of PID, the CDC recommends a 2-drug regimen of cefoxitin (2 g IV every 6 hours) or cefotetan (2 g IV every 12 hours) given in conjunction with doxycycline (100 mg IV or orally every 12 hours) or a 2-drug regimen of clindamycin (900 mg IV every 8 hours) and gentamicin (usually a 2-mg/kg IV or IM loading dose followed by 1.5 mg/kg every 8 hours).167 While there is some evidence that other parenteral cephalosporins (e.g., cefotaxime, ceftriaxone) may be effective for the treatment of PID,167,298,299 the CDC states that these drugs are less active than cefoxitin or cefotetan against anaerobic bacteria.167

When an oral regimen is used for the outpatient treatment of mild to moderately severe acute PID, the CDC recommends a regimen that consists of a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime given with oral doxycycline (with or without oral metronidazole).167 The optimal cephalosporin for the regimen is unclear, although cefoxitin has better anaerobic coverage and ceftriaxone has better coverage against N. gonorrhoeae .167

For additional information on treatment of PID, including information on follow-up and management of sexual partners, see Uses: Pelvic Inflammatory Disease, in the Cephalosporins General Statement 8:12.06.

Respiratory Tract Infections

Community-acquired Pneumonia

Cefotaxime is used for the treatment of community-acquired pneumonia (CAP).197,269,342 The American Thoracic Society (ATS) and IDSA recommend cefotaxime as an alternative to penicillin G or amoxicillin for treatment of community-acquired pneumonia (CAP) caused by penicillin-susceptible S. pneumoniae and as a preferred drug for treatment of CAP caused by penicillin-resistant S. pneumoniae , provided in vitro susceptibility has been demonstrated.269 IDSA and ATS also recommend use of cefotaxime in certain combination regimens used for empiric treatment of CAP.269

Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns; therapy may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing.269 The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation and whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., penicillin- or multidrug-resistant S. pneumoniae , enteric gram-negative bacilli, Ps. aeruginosa ).269

Most experts recommend that an empiric regimen for treatment of CAP include an anti-infective active against S. pneumoniae since this organism is the most commonly identified cause of bacterial pneumonia and causes more severe disease than many other common CAP pathogens.269,352 Pathogens most frequently involved in outpatient CAP include S. pneumoniae , M. pneumoniae , Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ), respiratory viruses, and H. influenzae .269 Pathogens most frequently involved in inpatient CAP in non-ICU patients are S. pneumoniae , M. pneumoniae , C. pneumoniae , H. influenzae , Legionella , and respiratory viruses.269 Patients with severe CAP admitted into the ICU usually have infections caused by S. pneumoniae , S. aureus , Legionella , gram-negative bacilli, or H. influenzae .269 Coverage against anaerobic bacteria usually is indicated only in classic aspiration pleuropulmonary syndrome in patients who had loss of consciousness as a result of alcohol or drug overdosage after seizures in patients with concomitant gingival disease or esophageal motility disorders.269

Inpatient treatment of CAP is initiated with a parenteral regimen, although therapy may be changed to an oral regimen if the patient is improving clinically, is hemodynamically stable, able to ingest drugs, and has a normally functioning GI tract.269 CAP patients usually have a clinical response within 3-7 days after initiation of therapy and a switch to oral therapy generally can be made during this period.269

For empiric inpatient treatment of CAP in non-ICU patients, IDSA and ATS recommend monotherapy with a fluoroquinolone (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin).269 For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) S. aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).269

For additional information on treatment of CAP, see Community-acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.

Septicemia

Cefotaxime is used for the treatment of bacteremia/septicemia caused by E. coli , Klebsiella , S. marcescens , S. aureus , and streptococci (including S. pneumoniae ).230

The choice of anti-infective agent for the treatment of sepsis syndrome should be based on the probable source of infection, causative organism, immune status of the patient, and local patterns of bacterial resistance.197 For initial treatment of life-threatening sepsis in adults, some clinicians recommend that a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftriaxone, ceftazidime), the fixed combination of piperacillin and tazobactam, or a carbapenem (doripenem, imipenem, meropenem) be used in conjunction with vancomycin; some experts also suggest including an aminoglycoside or fluoroquinolone during the initial few days of treatment.197

Typhoid Fever and Other Salmonella Infections

Typhoid Fever

Cefotaxime has been used in adults or children for the treatment of typhoid fever† (enteric fever) or septicemia caused by Salmonella typhi † or S. paratyphi †, including multidrug-resistant strains.275,306 Multidrug-resistant strains of S. typhi (i.e., strains resistant to ampicillin, chloramphenicol, and/or co-trimoxazole) have been reported with increasing frequency, and third generation cephalosporins (e.g., cefotaxime, ceftriaxone) and fluoroquinolones (e.g., ciprofloxacin, ofloxacin) are considered the agents of first choice for the treatment of typhoid fever or other severe infections known or suspected to be caused by these strains.197,275,304,305,306,307

Cefotaxime also has been used in the treatment of infections caused by nontyphi Salmonella , including bacteremia, osteomyelitis, and meningitis caused by S. typhimurium .306,308

Salmonella Gastroenteritis

Anti-infective therapy generally is not indicated in otherwise healthy individuals with uncomplicated (noninvasive) gastroenteritis caused by non-typhi Salmonella (e.g., S. enteritidis , S. 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 CDC,218 AAP,275 IDSA,245 and others197,304,412 recommend anti-infective therapy in individuals with severe Salmonella gastroenteritis and in those who are at increased risk of invasive disease. These individuals at increased risk include infants younger than 3-6 months of a individuals older than 50 years of a individuals with hemoglobinopathies, severe atherosclerosis or valvular heart disease, prostheses, uremia, chronic GI disease, or severe colitis; and individuals who are immunocompromised because of malignancy, immunosuppressive therapy, HIV infection, or other immunosuppressive illness.245,275,412

When an anti-infective agent is considered necessary in an individual with Salmonella gastroenteritis, the CDC,218 AAP,245 IDSA,245 and others197 recommend use of ceftriaxone, cefotaxime, a fluoroquinolone (should be used in children only if the benefits outweigh the risks and no alternative exists), ampicillin, amoxicillin, co-trimoxazole, or chloramphenicol, depending on the susceptibility of the causative organism.275,304,412

HIV-Infected Individuals

Because HIV-infected individuals with Salmonella gastroenteritis† are at high risk for bacteremia, the CDC, NIH, and IDSA recommend that such patients receive anti-infective treatment.412 These experts state that the initial drug of choice for the treatment of Salmonella gastroenteritis (with or without bacteremia) in HIV-infected adults is ciprofloxacin; other fluoroquinolones (levofloxacin, moxifloxacin) also are likely to be effective, but clinical data are limited.412 Depending on results of in vitro susceptibility testing of the causative organism, alternatives for treatment of Salmonella gastroenteritis in HIV-infected adults are co-trimoxazole or third generation cephalosporins (ceftriaxone, cefotaxime).412

HIV-infected individuals who have been treated for Salmonella bacteremia should be monitored for recurrence.412 The CDC, NIH, and IDSA state that long-term maintenance anti-infective therapy (secondary prophylaxis) to prevent recurrence should be considered for those with recurrent Salmonella bacteremia and also may be considered for those with recurrent gastroenteritis (with or without bacteremia) or those who have CD4⁺ T-cell counts less than 200 cells/mm³ and severe diarrhea.412 However, the value of such prophylaxis has not been established and the possible benefits must be weighed against the risks of long-term anti-infective exposure.412

Capnocytophaga Infections

Based on results of in vitro susceptibility tests that indicate that Capnocytophaga generally are inhibited by cefotaxime,312,314,315 some clinicians suggest that cefotaxime can be used in the treatment of infections caused by Capnocytophaga †.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 infections caused by the organism.347 C. canimorsus infection usually occurs as the result of a dog bite.316 The optimum regimen for the treatment of infections caused by Capnocytophaga has not been identified but some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftriaxone), a carbapenem (imipenem, meropenem), vancomycin, a fluoroquinolone, or clindamycin.197

Vibrio Infections

Vibrio parahaemolyticus Infections

Cefotaxime is one of several alternatives recommended for the treatment of severe cases of Vibrio parahaemolyticus † infection when anti-infective therapy is indicated in addition to supportive care.218 V. parahaemolyticus infection is a relatively rare foodborne illness that can occur as the result of ingestion of undercooked or raw fish or shellfish; the incubation period usually is 2-48 hours.218 The signs and symptoms of V. parahaemolyticus infection are watery diarrhea, abdominal cramps, and nausea and vomiting lasting 2-5 days.218 Although supportive care usually is sufficient, some clinicians recommend use of tetracycline, doxycycline, gentamicin, or cefotaxime in severe cases.218

Vibrio vulnificus Infections

Some clinicians suggest that cefotaxime is a drug of choice for the treatment of infections caused by V. vulnificus †.250 V. vulnificus can cause potentially fatal septicemia, wound infections, or gastroenteritis and generally is transmitted through ingestion of contaminated raw or undercooked seafood (especially raw oysters) or through contamination of a wound with seawater or seafood drippings.218,250,294,295 V. vulnificus is naturally present in marine environments, thrives in warm ocean water, and frequently is isolated from oysters and other shellfish harvested from the Gulf of Mexico and from US coastal waters along the Pacific and Atlantic ocean.250,295 Individuals with preexisting liver disease are at high risk for developing fatal septicemia following ingestion of seafood contaminated with V. vulnificus and debilitated or immunocompromised individuals (e.g., those with chronic renal impairment, cancer, diabetes mellitus, steroid-dependent asthma, chronic GI disease) or individuals with iron overload states (e.g., thalassemia, hemochromatosis) also are at increased risk for fatal infections.218,250,295 The incubation period for V. vulnificus infection reportedly is 1-7 days and the duration of illness usually is 2-8 days.218 In immunocompromised individuals, fever, nausea, myalgia, and abdominal cramps may occur as soon as 24-48 hours after ingestion of seafood contaminated with V. vulnificus and sepsis and cutaneous bullae may be present within 36 hours of the onset of symptoms.250

Because the case fatality rate for V. vulnificus septicemia exceeds 50% in immunocompromised individuals and those with preexisting liver disease, these individuals should be informed about the health hazards of ingesting raw or undercooked seafood (especially oysters), the need to avoid contact with seawater during the warm months, and the importance of using protective clothing (e.g., gloves) when handling shellfish.250,294 V. vulnificus infection should be considered in the differential diagnosis of fever of unknown etiology, and individuals who present with fever (especially when bullae, cellulitis, or wound infection is present) and who have preexisting liver disease or are immunocompromised should be questioned regarding a history of raw oyster ingestion or seawater contact.250 While optimum anti-infective therapy for the treatment of V. vulnificus infections has not been identified, use of a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.197,218,250 Because of the high fatality rate associated with V. vulnificus infections, anti-infective therapy should be initiated promptly if indicated.250,294

Perioperative Prophylaxis

Cefotaxime has been used for perioperative prophylaxis in patients undergoing liver transplantation†, and some experts recommend cefotaxime in conjunction with ampicillin as a regimen of choice for such prophylaxis in patients undergoing this procedure.169

Cefotaxime has been used perioperatively to reduce the incidence of infection in patients undergoing contaminated or potentially contaminated surgery, including biliary tract,169 colorectal,169 and other intra-abdominal or GI procedures (e.g., appendectomy),169,230 genitourinary surgery,169,230 or abdominal or vaginal hysterectomy,169,230 and in patients undergoing cesarean section.230 However, other anti-infectives (e.g., cefazolin) usually are recommended for perioperative prophylaxis in patients undergoing these procedures.168,169

A first or second generation cephalosporin (cefazolin, cefoxitin, cefotetan, cefuroxime) generally is preferred when a cephalosporin is used for perioperative prophylaxis.168,169 Third generation cephalosporins (cefotaxime, ceftriaxone, ceftazidime) and fourth generation cephalosporins (cefepime) are not usually recommended for 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.168,169 (See Uses: Perioperative Prophylaxis in the Cephalosporins General Statement 8:12.06.)

Reconstitution and Administration

Cefotaxime sodium is administered IV or by deep IM injection.230,366,367 The drug should be given IV rather than IM in patients with septicemia, bacteremia, peritonitis, meningitis, or other severe or life-threatening infections or in patients with lowered resistance resulting from debilitating conditions (e.g., malnutrition, trauma, surgery, diabetes, heart failure, malignancy), particularly if shock is present.

Intermittent IV Injection

For direct intermittent IV administration, 10 mL of sterile water for injection should be added to a vial labeled as containing 500 mg, 1 g, or 2 g of cefotaxime to provide a solution containing approximately 50, 95, or 180 mg of cefotaxime per mL, respectively.230 A solution of 1 g of cefotaxime per 14 mL of sterile water for injection is isotonic.230

The appropriate dose may then be injected directly into a vein over a 3- to 5-minute period or slowly into the tubing of a freely flowing compatible IV solution.230 Cefotaxime should not be injected IV over less than 3 minutes since rapid (over less than 1 minute) injection was consistently associated with potentially life-threatening arrhythmias during postmarketing surveillance.230

Intermittent or Continuous IV Infusion

For intermittent or continuous IV infusion, 50 or 100 mL of 0.9% sodium chloride injection or 5% dextrose injection should be added to an infusion bottle labeled as containing 1 or 2 g of cefotaxime or, alternatively, reconstituted solutions of cefotaxime may be further diluted with 50 mL to 1 L of a compatible IV solution. ADD-Vantage^® vials or infusion bottles labeled as containing 1 or 2 g of cefotaxime or the 10-g pharmacy bulk package of cefotaxime should be reconstituted according to the manufacturer's directions. The cefotaxime bulk package is not intended for direct IV infusion; doses of the drug from the reconstituted bulk package must be further diluted in a compatible IV infusion solution prior to administration.

Thawed solutions of the commercially available frozen premixed cefotaxime sodium injection should be administered only by intermittent or continuous IV infusion.230 The frozen injections should be thawed at room temperature or under refrigeration (5°C or lower); the injection should not be thawed by warming in a water bath or by exposure to microwave radiation.230 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.230 After thawing to room temperature, the injection should be agitated and the container checked for minute leaks by firmly squeezing the bag.230 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.230 Additives should not be introduced into the injection container.230 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.230

Other IV solutions flowing through a common administration tubing or site should be discontinued while cefotaxime is being infused unless the solutions are known to be compatible and the flow-rate is adequately controlled.

Rate of Administration

Intermittent IV infusions of cefotaxime are generally infused over 20-30 minutes; solutions should preferably be infused via butterfly or scalp vein-type needles.

IM Injection

IM injections of cefotaxime are prepared by adding 2, 3, or 5 mL of sterile or bacteriostatic water for injection to a vial labeled as containing 500 mg, 1 g, or 2 g of the drug.230 Resultant solutions contain approximately 230, 300, or 330 mg of cefotaxime per mL, respectively.230

IM injections should be made deeply into a large muscle mass such as the upper outer quadrant of the gluteus maximus; aspiration should be performed to avoid inadvertent injection into a blood vessel.230,366 The manufacturers state that if an IM dose of 2 g of cefotaxime is indicated, the dose should be divided and administered at 2 different injection sites.230,366 However, because large IM doses of cefotaxime may be painful, some clinicians recommend that large doses of the drug be given IV.

Dosage

Dosage of cefotaxime sodium is expressed in terms of cefotaxime and is identical for IM or IV administration.

Adult Dosage

The usual adult dosage of cefotaxime for the treatment of uncomplicated infections is 1 g IM or IV every 12 hours.230,366,367 Moderate to severe infections usually respond to 1-2 g IM or IV every 8 hours, but some infections (e.g., septicemia) should be treated with 2 g IV every 6-8 hours.230,366,367 Severe or life-threatening infections may require 2 g IV every 4 hours.230,366,367

The maximum adult dosage recommended by the manufacturers is 12 g daily.230,366,367

Meningitis and Other CNS Infections

For the treatment of meningitis or other CNS infections caused by susceptible bacteria, the usual adult dosage of cefotaxime is 2 g IV every 6 hours for 7-21 days.230,296 Some clinicians recommend that adults receive 8-12 g daily in divided doses every 4-6 hours for the treatment of meningitis.365 Other clinicians recommend that patients with meningitis known or suspected to be caused by S. pneumoniae receive an initial cefotaxime dosage of 350 mg/kg daily given in 4 divided doses; if results of in vitro susceptibility testing indicate that the organism is susceptible to penicillin, dosage can be reduced to 225 mg/kg daily given in 3 divided doses.327,335

While 7 days of cefotaxime therapy may be adequate for the treatment of uncomplicated meningitis caused by susceptible Haemophilus influenzae or Neisseria meningitidis , at least 10-14 days of therapy is recommended for complicated cases or meningitis caused by Streptococcus pneumoniae and at least 21 days of therapy is recommended for meningitis caused by susceptible Enterobacteriaceae (e.g., Escherichia coli , Klebsiella ).296,318

Gonorrhea and Associated Infections

For the treatment of uncomplicated urethral, cervical, or rectal gonorrhea caused by susceptible N. gonorrhoeae , adults and adolescents should receive a single 500-mg IM dose of cefotaxime.167,230,366,367 The manufacturers recommend a single 1-g IM dose for the treatment of rectal gonorrhea in males.230,366,367

For the treatment of disseminated gonorrhea†, adults and adolescents should receive 1 g of cefotaxime IV every 8 hours.167 Parenteral cefotaxime should be continued for 24-48 hours after improvement begins; therapy can then be switched to oral cefixime to complete at least 1 week of therapy.167

GI Infections

If cefotaxime is used as an alternative for empiric treatment of infectious diarrhea† in HIV-infected adults, 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 8 hours.412 If there is no clinical response after 5-7 days, stool culture and in vitro susceptibility testing should be considered.412

If cefotaxime is used as an alternative for the treatment of Salmonella gastroenteritis† (with or without bacteremia) in HIV-infected adults, the CDC, NIH, and IDSA recommend a dosage of 1 g IV every 8 hours.412 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/mm³.412

Lyme Disease

If cefotaxime is used for the treatment of early Lyme disease† in adults with acute neurologic disease manifested by meningitis or radiculopathy, the Infectious Diseases Society of America (IDSA) and other clinicians recommend a dosage of 2 g IV every 8 hours for 14 days (range: 10-28 days).273,351,354

If cefotaxime is used 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, the IDSA and other clinicians recommend a dosage of 2 g IV every 8 hours for 14 days (range: 14-21 days).351,354 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.351

If cefotaxime is used when a parenteral regimen is indicated for the treatment of Lyme arthritis† in patients with evidence of neurologic disease or when arthritis has not responded to an oral regimen, the IDSA recommends that adults receive 2 g IV every 8 hours for 14 days (range: 14-28 days).351

If cefotaxime is used for the treatment of late neurologic Lyme disease† affecting the CNS or peripheral nervous system, the IDSA recommends that adults receive 2 g IV every 8 hours for 14 days (range: 14-28 days).273,351

Respiratory Tract Infections

For the treatment of community-acquired pneumonia (CAP) in adults who are hospitalized for inpatient treatment, cefotaxime usually is given in a dosage of 1 g every 6-8 hours.269

If used for empiric treatment of CAP, cefotaxime is used in conjunction with other anti-infectives.269 (See Community-acquired Pneumonia under Uses: Respiratory Tract Infections.)

Perioperative Prophylaxis

If cefotaxime is used for perioperative prophylaxis in contaminated or potentially contaminated surgery, the manufacturers recommend that adults receive 1 g IM or IV given 30-90 minutes prior to surgery.230,366,367 If cefotaxime is used prophylactically in patients undergoing cesarean section, the manufacturers recommend 1 g given IV as soon as the umbilical cord is clamped, followed by 1 g IM or IV 6 and 12 hours after the first dose.230,366,367

Although not usually considered a drug of choice for perioperative prophylaxis168,301 (see Uses: Perioperative Prophylaxis), if cefotaxime is used for perioperative prophylaxis some experts recommend that adults receive 1 g of cefotaxime (2 g in obese patients) within 60 minutes prior to surgical incision.169 If the procedure is prolonged (longer than 3-4 hours) or if major blood loss occurs, additional intraoperative doses of cefotaxime may be given every 3 hours.169 The duration of prophylaxis should be less than 24 hours for most procedures;168 there is no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.168,169

Pediatric Dosage

General Dosage for Neonates

The usual dosage of cefotaxime recommended by the manufacturers for premature or full-term neonates less than 1 week of age is 50 mg/kg every 12 hours and the usual dosage for neonates 1-4 weeks of age is 50 mg/kg every 8 hours.230,366,367

The American Academy of Pediatrics (AAP) recommends that neonates 7 days of age or younger receive IV or IM cefotaxime in a dosage of 50 mg/kg every 12 hours, regardless of weight.275 For neonates 8-28 days of age, the AAP recommends a dosage of 50 mg/kg every 8-12 hours for those weighing 2 kg or less and 50 mg/kg every 8 hours for those weighing more than 2 kg.275

General Dosage for Infants and Children

Children weighing 50 kg or more should receive the usual daily adult dosage, but dosage should not exceed 12 g daily.230,366,367

The manufacturers recommend that children 1 month to 12 years of age weighing less than 50 kg receive 50-180 mg/kg daily given in 4-6 equally divided doses; the higher dosages should be used for more severe or serious infections, including meningitis.230,366,367

The AAP recommends that pediatric patients beyond the neonatal period receive cefotaxime in a dosage of 50-180 mg/kg daily given in 3 or 4 equally divided doses for the treatment of mild to moderate infections or 200-225 mg/kg daily given in 4 or 6 equally divided doses for the treatment of severe infections.275

Meningitis and Other CNS Infections

For the treatment of meningitis caused by susceptible bacteria, the manufacturers recommend that children 1 month to 12 years of age who weigh less than 50 kg receive a cefotaxime dosage at the high end of the range of 50-180 mg/kg daily.230,366,367

Some clinicians recommend that infants and children younger than 18 years of age with meningitis receive cefotaxime in a dosage of 50 mg/kg IV every 6 hours.296 Other clinicians recommend a cefotaxime dosage of 100-150 mg/kg daily given in divided doses every 8-12 hours in neonates 7 days of age or younger, 150-200 mg/kg daily given in divided doses every 6-8 hours in neonates 8-28 days of age, and 225-300 mg/kg daily given in divided doses every 6-8 hours in older infants and children.365

The AAP states that a cefotaxime dosage up to 300 mg/kg daily given in 4 or 6 divided doses can be used for the treatment of meningitis in pediatric patients beyond the neonatal period.275

While 7 days of 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 recommended for complicated cases or for meningitis caused by S. pneumoniae and at least 21 days is recommended for meningitis caused by susceptible Enterobacteriaceae (e.g., E. coli , Klebsiella ).275,296,328

Gonorrhea and Associated Infections

The usual dosage of cefotaxime for the treatment of disseminated gonococcal infection† (e.g., sepsis, arthritis, meningitis) or gonococcal scalp abscesses† in neonates is 25 mg/kg IV or IM every 12 hours for 7 days; if meningitis is documented, the drug should be continued for 10-14 days.167,275

Lyme Disease

If cefotaxime is used for the treatment of early Lyme disease† in children with acute neurologic disease manifested by meningitis or radiculopathy, the IDSA and other clinicians recommend a dosage of 150-200 mg/kg daily (up to 6 g daily) given IV in divided doses every 6-8 hours for 14 days (range: 10-28 days).273,351,354

If cefotaxime is used 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, the IDSA and other clinicians recommend that children receive a dosage of 150-200 mg/kg daily (up to 6 g daily) given IV in divided doses every 6-8 hours for 14 days (range: 14-21 days).351,354 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.351

If cefotaxime is used when a parenteral regimen is indicated for the treatment of Lyme arthritis† in patients with evidence of neurologic disease or when arthritis has not responded to an oral regimen, the IDSA recommends that children receive a dosage of 150-200 mg/kg daily (up to 6 g daily) given IV in divided doses every 6-8 hours for 14 days (range: 14-28 days).351

If cefotaxime is used for the treatment of late neurologic Lyme disease† affecting the CNS or peripheral nervous system, the IDSA recommends that children receive a dosage of 150-200 mg/kg daily (up to 6 g daily) given IV in divided doses every 6-8 hours for 14 days (range: 14-28 days).273,351

Duration of Therapy

The duration of cefotaxime therapy depends on the type of infection but should generally be continued for at least 48-72 hours after the patient becomes afebrile or evidence of eradication of the infection is obtained. Although other drugs generally are preferred, if cefotaxime is used in infections caused by group A β-hemolytic streptococci, therapy should be continued for at least 10 days to decrease the risk of rheumatic fever or glomerulonephritis. Chronic urinary tract infections may require several weeks of therapy, and bacteriologic and clinical assessments should be made frequently during therapy and for several months after therapy is discontinued.

Dosage in Renal and Hepatic Impairment

Modification of the usual dosage of cefotaxime is unnecessary in patients with creatinine clearances of 20 mL/minute or greater per 1.73 m².230 However, in patients with creatinine clearances less than 20 mL/minute per 1.73 m², doses and/or frequency of administration should be modified in response to the degree of renal impairment.230 The manufacturers recommend that these patients receive half the usual dose of cefotaxime at the usual time interval.230,366,367

In patients undergoing hemodialysis, some clinicians recommend that 0.5-2 g be given as single daily doses and that a supplemental dose of cefotaxime be given after each dialysis period.

Although serum half-life and clearance of cefotaxime and its major metabolite may be prolonged in patients with impaired hepatic function,117,289 dosage adjustments are not necessary in such patients unless renal function also is impaired.289,290

Dermatologic and Sensitivity Reactions

Hypersensitivity reactions have been reported to occur in approximately 2% of patients receiving cefotaxime. These reactions include rash (maculopapular or erythematous), pruritus, fever, and eosinophilia.230 Urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred rarely.230 If a severe hypersensitivity reaction occurs during cefotaxime therapy, the drug should be discontinued and the patient given appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.

Positive direct antiglobulin (Coombs') test results have also been reported occasionally in patients receiving cefotaxime;230 however, it is not clear whether the mechanism of this reaction is immunologic in nature.

Local Effects

The most frequent adverse reactions to cefotaxime are local reactions at the injection site which occur in approximately 4% of patients. IV administration has caused inflammation,230 phlebitis, and thrombophlebitis and IM administration has caused pain, induration, and tenderness at the injection site. Extensive perivascular extravasation of cefotaxime may result in tissue damage requiring surgical intervention; however, in most cases, perivascular extravasation responds to changing the infusion site.230 To minimize the potential for tissue inflammation, the manufacturers recommend that IV infusion sites be monitored regularly and changed appropriately.230

GI Effects

Adverse GI effects including anorexia, diarrhea, nausea, vomiting, abdominal pain, and colitis have occurred in approximately 1% of patients receiving cefotaxime.

Treatment with anti-infectives alters the normal colon flora and may permit overgrowth of Clostridium difficile .230,342,344,345 C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including cefotaxime, and may range in severity from mild diarrhea to fatal colitis.230,342,344,345 C. difficile produces toxins A and B which contribute to the development of CDAD;230,342 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.230

CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy and managed accordingly.230,342,344,345 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.230,342

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible.230,342 Patients should be managed with appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.230,342,344,345

Hematologic Effects

Transient neutropenia, granulocytopenia, leukopenia, eosinophilia, or thrombocytopenia have occurred in less than 1% of patients receiving cefotaxime. Agranulocytosis reportedly may occur rarely with cefotaxime treatment, particularly during prolonged therapy; therefore, blood cell counts should be performed in patients receiving treatment courses lasting for more than 10 days. Hemolytic anemia has also been reported rarely. Prolongation of the prothrombin time and hypoprothrombinemia have been reported only rarely in patients receiving cefotaxime.225

Renal Effects

Transient increases in BUN and/or serum creatinine concentrations and interstitial nephritis230 have been reported in a few patients receiving cefotaxime. A transient increase in urinary concentration of alanine aminopeptidase, which may be an indication of transient tubular damage, has been reported in a few patients receiving the drug. Most studies indicate that cefotaxime is not nephrotoxic and that urine concentrations of alanine aminopeptidase are usually unchanged during therapy with the drug.

Other Adverse Effects

Transient increases in serum AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase concentrations have been reported in less than 1% of patients receiving cefotaxime.

Headache, agitation, confusion, fatigue, and nocturnal perspiration have also been reported in less than 1% of patients receiving the drug. Seizures have been reported with some cephalosporins,

During postmarketing surveillance, potentially life-threatening arrhythmias were reported in several patients who received cefotaxime by rapid (less than 1 minute) bolus injection through a central venous catheter.230

Precautions and Contraindications

Prior to initiation of cefotaxime therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cefotaxime, cephalosporins, penicillins, or other drugs. There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins and cephamycins; however, the true incidence of cross-allergenicity among these anti-infectives has not been established.226,227,230,302,303 Cefotaxime is contraindicated in patients with a history of allergic reactions to the drug or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins. Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.303 Although it has not been definitely proven that allergic reactions to antibiotics are more frequent in atopic individuals, the manufacturers state that cefotaxime should be used with caution in patients with a history of allergy, particularly to drugs.

To reduce development of drug-resistant bacteria and maintain effectiveness of cefotaxime and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.230 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.230 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.230

Patients should be advised that antibacterials (including cefotaxime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).230,366 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefotaxime or other antibacterials in the future.230,366

Like other anti-infectives, prolonged use of cefotaxime may result in overgrowth of nonsusceptible organisms, especially Candida and Pseudomonas. Vaginitis and moniliasis have occurred in less than 1% of patients receiving cefotaxime. Resistant strains of some organisms, especially Enterobacter, Ps. aeruginosa , and Serratia , have developed during therapy with cefotaxime. Careful observation of the patient during cefotaxime therapy is essential. If suprainfection or superinfection occurs, appropriate therapy should be instituted.

Because CDAD has been reported with the use of cefotaxime or other cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after cefotaxime therapy.230,345,344,345 (See Cautions: GI Effects.) Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually resolves when the drug is discontinued; however, they should contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.230 Cefotaxime should be used with caution in patients with a history of GI disease, particularly colitis.230

Seizures have been reported with several cephalosporins, particularly in patients with renal impairment in whom dosage of the drug was not reduced.230 If seizures occur during cephalosporin therapy, the drug should be discontinued and anticonvulsant therapy initiated as clinically indicated.230

Pediatric Precautions

Cefotaxime is well tolerated in pediatric patients, and adverse effects reported in children receiving the drug are similar to those reported in adults.291 A retrospective review of children 3 months to 18 years of age who received cefotaxime indicates that adverse effects occurred in up to 2.5% of these children and included adverse local reactions, rash, and adverse GI effects such as diarrhea and vomiting.

Safety of the chemical components that may leach out of the plastic containing commercially available frozen cefotaxime sodium injections has not been established in children.230

Geriatric Precautions

In clinical studies of cefotaxime sodium, there were no overall differences in safety or efficacy between geriatric adults 65 years of age or older and younger adults.230,366,367 Other clinical experience revealed no evidence of age-related differences; however, the possibility that some geriatric patients may exhibit increased sensitivity to the drug cannot be ruled out.230,366,367

Cefotaxime is substantially excreted by the kidney, and the risk of severe adverse reactions may be increased in patients with impaired renal function.230,366,367 Because geriatric patients are more likely to have decreased renal function, dosage should be selected with caution in these patients and renal function monitoring may be useful.230,366,367

Mutagenicity and Carcinogenicity

Cefotaxime was not mutagenic in the mouse micronucleus test or the Ames test.230 Studies have not been performed to date to evaluate the carcinogenic potential of cefotaxime.230

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in mice or rats using IV cefotaxime dosages up to 1.2 g/kg daily (0.4 or 0.8 times, respectively, the usual human dosage based on mg/m³) have not revealed evidence of embryotoxicity or teratogenicity.230 However, the offspring of rats that received 1.2 g/kg of cefotaxime weighed less at birth and also remained smaller during 21 days of nursing than offspring of rats that did not receive the drug.230 There are no adequate and controlled studies to date using cefotaxime in pregnant women, and the drug should be used during pregnancy only when clearly needed.230

Fertility

There was no evidence of impaired fertility in rats given cefotaxime subcutaneously at dosages up to 250 mg/kg daily or in mice given the drug IV at dosages up to 2 g/kg daily (0.2 or 0.7 times, respectively, the recommended human dosage based on mg/m³).230

Lactation

Because cefotaxime is distributed into milk, the drug should be used with caution in nursing women.230

Aminoglycosides

In vitro studies indicate that the antibacterial activity of cefotaxime and aminoglycosides may be additive or synergistic against some organisms including some strains of Ps. aeruginosa and S. marcescens. However, synergism is unpredictable and antagonism has also occurred in vitro when cefotaxime was used in combination with an aminoglycoside.

Concurrent use of aminoglycosides and cephalosporins may increase the risk of nephrotoxicity during therapy. Although this effect has not been reported to date with cefotaxime, the manufacturers state that the possibility that nephrotoxicity may be potentiated if the drug is used concomitantly with an aminoglycoside should be considered.

Other Anti-infective Agents

In one in vitro study which used the checkerboard technique to assess synergism, a combination of cefotaxime and ampicillin appeared to be partially additive or synergistic against a few strains of group B streptococci. However, when the killing-curve technique was used to assess synergism, the combination was no more effective than cefotaxime alone against these organisms. In one in vitro study, a combination of cefotaxime and clindamycin was neither synergistic nor antagonistic against Enterobacteriaceae.

Laboratory Test Interferences

Immunohematology Tests

Positive direct antiglobulin (Coombs') test results have been reported in some patients receiving cefotaxime.230 This reaction may interfere with hematologic studies or transfusion cross-matching procedures.

Tests for Glucose and Creatinine

Although other currently available cephalosporins reportedly cause false-positive results in urine glucose determinations using cupric sulfate solution (Benedict's reagent, Clinitest^®) and may cause falsely elevated serum or urine creatinine values when the Jaffé reaction is used, cefotaxime does not appear to interfere with these laboratory tests.

Acute Toxicity

In neonatal and adult mice and rats, acute overdosage of cefotaxime resulted in significant mortality at parenteral dosages exceeding 6 g/kg daily.230 Common toxic signs in those that died included a decrease in spontaneous activity, tonic and clonic convulsions, dyspnea, hypothermia, and cyanosis.230

Acute overdosage of cefotaxime in patients has most frequently resulted in increased serum concentrations of BUN and creatinine, but most cases were not associated with overt toxicity.230 If acute overdosage occurs, the patient should be closely observed and given supportive treatment.230

Mechanism of Action

Cefotaxime has a mechanism of action similar to that of other cephalosporins. For information on the mechanism of action of cephalosporins, see Mechanism of Action in the Cephalosporins General Statement 8:12.06.

The target enzymes of β-lactam antibiotics have been classified as penicillin-binding proteins (PBPs) and appear to vary substantially among bacterial species. Studies evaluating the binding of cefotaxime to PBPs indicate that the drug has a high affinity for PBPs 1a, 1b, and 3 of Escherichia coli and PBPs 1a, 1b, 3, and 4 of Pseudomonas aeruginosa. The affinities of various β-lactam antibiotics for different PBPs appear to explain the differences in morphology which occur in susceptible organisms following exposure to different β-lactam antibiotics and may also explain differences in the spectrum of activity of β-lactam antibiotics which are not due to the presence or absence of β-lactamases.

Spectrum

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

Like other currently available parenteral third generation cephalosporins (e.g., ceftazidime, ceftriaxone), cefotaxime generally is less active in vitro against susceptible staphylococci than first generation cephalosporins but has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins. The spectrum of activity of cefotaxime closely resembles that of ceftriaxone. In vitro on a weight basis, the activity of cefotaxime against most susceptible Enterobacteriaceae is approximately equal to that of ceftriaxone. Cefotaxime is inactive against Chlamydia , fungi, and viruses.

The major metabolite of cefotaxime, desacetylcefotaxime, is also microbiologically active. In vitro, desacetylcefotaxime has only about 10% of the antibacterial activity of cefotaxime. However, desacetylcefotaxime is more active in vitro against susceptible gram-positive aerobic bacteria than is cefazolin or cefoxitin. It has been suggested that the antibacterial activity of desacetylcefotaxime may be clinically important in infections in patients with impaired renal function or in infections in organs or tissues where desacetylcefotaxime accumulates. Preliminary data indicate that the antibacterial activities of cefotaxime and desacetylcefotaxime are additive or synergistic against cefotaxime-susceptible S. aureus and Enterobacteriaceae.

In Vitro Susceptibility Testing

For most organisms, inoculum size, pH, test media, and presence of serum do not appear to influence results of in vitro cefotaxime susceptibility tests. However, results of susceptibility tests for some gram-negative bacilli (especially Proteus, Providencia, Pseudomonas aeruginosa, Klebsiella , and Serratia marcescens ) may be greatly affected by the size of the inoculum.

Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to cefotaxime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.203

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

Gram-positive Aerobic Bacteria

In vitro, cefotaxime concentrations of 0.5 mcg/mL or less inhibit most strains of Streptococcus pneumoniae , S. pyogenes (group A β-hemolytic streptococci), and S. agalactiae (group B streptococci). Some strains of viridans streptococci are inhibited in vitro by cefotaxime concentrations of 4 mcg/mL or less. In one study, the MIC₅₀ and MIC₉₀ of cefotaxime for the S. milleri group of viridans streptococci ( S. anginosus , S. constellatus , S. intermedius ) were 0.25 and 0.5 mcg/mL, respectively.350 Cefotaxime concentrations of 4 mcg/mL or less inhibit most strains of Staphylococcus aureus in vitro. Cefotaxime is active in vitro against most strains of penicillinase-producing S. aureus ; however, almost all strains of staphylococci resistant to penicillinase-resistant penicillins are also resistant to cefotaxime. The MIC₉₀ (minimum inhibitory concentration of the drug at which 90% of strains are inhibited) of cefotaxime for S. epidermidis generally is 4.8-16 mcg/mL,2,48,50,70,80,239,247,248 although lower MIC₉₀s have been reported occasionally;246,248 in a few studies, however, the MIC₉₀ was 64 mcg/mL or greater.236,241,242 Listeria monocytogenes 236,239,241,242 and enterococci, including E. faecalis (formerly S. faecalis ),48,59,66,70,80,106,109,255,256,258,259,260,261 generally are resistant to the drug. Strains of S. pneumoniae with MICs of 2 mcg/mL or greater generally are considered resistant to cefotaxime.202,203

The MIC₉₀ of desacetylcefotaxime reported for susceptible S. pneumoniae and S. pyogenes is 4 mcg/mL or less. S. aureus is generally resistant to desacetylcefotaxime.

Gram-negative Aerobic Bacteria

Cefotaxime is active in vitro against a wide variety of gram-negative bacteria including most Enterobacteriaceae and some strains of Pseudomonas aeruginosa. Cefotaxime is active against some gram-negative bacteria that are resistant to first and second generation cephalosporins and currently available penicillins and aminoglycosides, especially Escherichia coli, Klebsiella pneumoniae , and Serratia marcescens.

Enterobacteriaceae

Generally, cefotaxime is active in vitro against the following Enterobacteriaceae: Citrobacter freundii, C. diversus, Enterobacter aerogenes, E. cloacae, Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Morganella morganii (formerly Proteus morganii ), Proteus mirabilis, P. vulgaris , Providencia stuartii (formerly group B Proteus inconstans ), P. rettgeri (formerly Proteus rettgeri ), Salmonella, Serratia marcescens , Shigella , and Yersinia enterocolitica . The MIC₉₀ of cefotaxime for many of these gram-negative bacilli is 4 mcg/mL or less. However, the MIC₉₀ of cefotaxime for C. freundii , E. aerogenes , E. cloacae , M. morganii , and Serratia generally ranges from 0.1-32 mcg/mL,2,61,64,65,68,69,72,78,80,109,235,236,237,239,240,242,248 although higher MIC₉₀s have been reported.61,65,69,109,235,237,240,242,248 The MIC₉₀ of desacetylcefotaxime reported for susceptible E. coli, K. pneumoniae, P. mirabilis , and Providencia stuartii is 4 mcg/mL or less; E. aerogenes, E. cloacae, M. morganii, P. vulgaris , and S. marcescens are generally resistant to desacetylcefotaxime.

Pseudomonas

The in vitro activity of cefotaxime against Pseudomonas is variable. Although some strains of Ps. aeruginosa and Ps. maltophilia ( Stenotrophomonas maltophilia ) are inhibited in vitro by cefotaxime concentrations of 32 mcg/mL or less, most strains of these organisms require cefotaxime concentrations of 64 mcg/mL or greater for in vitro inhibition and are therefore considered resistant to the drug. Cefotaxime is less active in vitro against susceptible Ps. aeruginosa than is ceftazidime or some extended-spectrum penicillins. Ps. aeruginosa generally is resistant to desacetylcefotaxime.

Other Gram-negative Aerobic Bacteria

Cefotaxime is active in vitro against Haemophilus influenzae (including ampicillin-resistant strains) and H. parainfluenzae . The MIC₉₀s of cefotaxime reported for H. influenzae and H. parainfluenzae are 0.01-0.8 and 0.024-4 mcg/mL, respectively, and the MIC₉₀ of desacetylcefotaxime reported for H. influenzae is 4 mcg/mL or less.

Cefotaxime is active in vitro against Neisseria meningitidis and Neisseria gonorrhoeae. The MIC₉₀ of cefotaxime reported for N. gonorrhoeae (including both penicillinase-producing and nonpenicillinase-producing strains) is 0.1-0.4 mcg/mL.

Both β-lactamase- and non-β-lactamase-producing strains of Moraxella catarrhalis are inhibited in vitro by cefotaxime concentrations of 0.03-0.5 mcg/mL.232,236,240,244

Cefotaxime is active in vitro against Eikenella corrodens , and the MIC₉₀ of the drug for this organism generally is 0.06-0.5 mcg/mL.220,221,249 Campylobacter fetus subsp. jejuni , an organism that can be microaerophilic or anaerobic, generally is inhibited in vitro by cefotaxime concentrations of 2-6.25 mcg/mL.222,223

Although cefotaxime has some activity in vitro against Acinetobacter ,2,61,64,75,78,80,106,109,230,235,238,239,240,248 the MIC₉₀ of the drug generally ranges from 8-32 mcg/mL for A. calcoaceticus var. lwoffi and from 16-32 mcg/mL for A. calcoaceticus var. anitratus ;64,75,106,235,238,239,240,241,248 higher MIC₉₀s also have been reported.61,109,236,237,248

In vitro, some strains of Bartonella bacilliformis are inhibited by cefotaxime concentrations of 0.03-0.12 mcg/mL.349

While some strains of Burkholderia cepacia (formerly Pseudomonas cepacia ) are inhibited in vitro by cefotaxime concentrations of 16 mcg/mL, the MIC₉₀ of the drug for this organism is 64 mcg/mL and most strains are resistant to the drug.317

Cefotaxime is active in vitro against Capnocytophaga .312,314,315 In an in vitro study, the MIC₉₀ of cefotaxime for Capnocytophaga was 0.25 mcg/mL.314 Cefotaxime-resistant strains of C. sputigena (formerly CDC group DF-1) have been reported.313

Vibrio vulnificus may be inhibited in vitro by cefotaxime concentrations of 0.03 mcg/mL.292 While the clinical importance is unclear, results of an in vitro study and a study in mice indicate that the combination of cefotaxime and minocycline is more active against V. vulnificus than either anti-infective alone.292,293

Anaerobic Bacteria

Cefotaxime is active in vitro against Bacteroides, Eubacterium, Fusobacterium, Peptococcus, Peptostreptococcus, Propionibacterium , and Veillonella. Cefotaxime is also active against some strains of Clostridium including C. perfringens ; however, C. difficile is usually resistant to the drug.

Although the MIC₉₀ of cefotaxime reported for most susceptible anaerobes is 16 mcg/mL or less, cefotaxime concentrations of 16-64 mcg/mL are generally required in vitro to inhibit Bacteroides (including B. fragilis ). In vitro, cefotaxime is less active than cefoxitin against susceptible B. fragilis.

Spirochetes

Borrelia burgdorferi , the causative organism of Lyme disease, reportedly may be inhibited in vitro by a cefotaxime concentration of 0.12 mcg/mL.265

Resistance

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

Because cefotaxime contains an α- syn -methoximino group which protects the β-lactam ring from hydrolysis by many penicillinases and cephalosporinases, cefotaxime is more resistant to hydrolysis by most β-lactamases than first and second generation cephalosporins. Cefotaxime is generally resistant to hydrolysis by β-lactamases classified as Richmond-Sykes types I, II, III, IV, and V, and most penicillinases produced by S. aureus. However, β-lactamases produced by B. fragilis and P. vulgaris can slowly hydrolyze cefotaxime.

Resistant strains of some organisms, especially Enterobacter, Ps. aeruginosa , or Serratia , have developed during therapy with cefotaxime. Strains of Ps. aeruginosa which are only moderately susceptible to cefotaxime in vitro at the beginning of therapy appear to be especially likely to become resistant during therapy.

Like most cephalosporins and penicillins, cefotaxime is inactivated by inducible, chromosomally mediated β-lactamases produced by some strains of Citrobacter , Enterobacter , Pseudomonas , and Serratia .215,216 Therefore, organisms that possess inducible β-lactamases are usually resistant to cefotaxime following derepression of the enzymes.215,216 Inducible β-lactamases may be derepressed by mutation to a stable derepressed state or may be reversibly derepressed by an enzyme inducer.216,217 Cefoxitin and imipenem are potent inducers of these enzymes, and in vitro exposure of organisms possessing these enzymes to these drugs results in resistance to cefotaxime as well as to many other β-lactam antibiotics.215,216,217 Inducible β-lactamases inactivate cephalosporins and penicillins either by hydrolyzing the drugs or by binding to them to prevent access to penicillin-binding proteins (PBPs).215,216,217 The clinical importance of these inducible β-lactamases is unclear, but emergence of cefotaxime resistance in some organisms during therapy with the drug may be related to these enzymes.215,216,217

Strains of S. pneumoniae considered resistant to cefotaxime have been reported with increasing frequency.202,277,279,280 These strains generally have intermediate- or high-level resistance to penicillin G as well as decreased susceptibility to third generation cephalosporins.202,277,280 Resistance to cefotaxime in S. pneumoniae appears to be related to alterations in the PBPs of the organism.202

Tolerance to cefotaxime has been reported to occur in some bacteria including some strains of Enterobacter, Proteus , and Ps. aeruginosa. In vitro, tolerant bacteria have a minimum bactericidal concentration (MBC) of cefotaxime which is much greater than the MIC of the drug. Bacteria which are tolerant to cefotaxime appear to be inhibited but not necessarily killed by the drug. Preliminary studies suggest that tolerant organisms may have decreased concentrations of autolysins or an increased concentration of an unidentified inhibitor of autolysis. Tolerance may be important clinically since infections caused by these organisms may persist during cefotaxime therapy despite in vitro susceptibility tests which indicate that the organisms are susceptible to the drug.

Pharmacokinetics

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

The antibacterial activity of both cefotaxime and its major metabolite, desacetylcefotaxime, must be considered when attempting to correlate the pharmacokinetics with the therapeutic effect of the drug. In early published studies on the pharmacokinetics of cefotaxime, microbiologic assays were used to determine body fluid and tissue concentrations of the drug.6,8,9,10,11,12,15,19,20,21 Microbiologic assays which used test organisms susceptible to cefotaxime but resistant to desacetylcefotaxime accurately reflect concentrations of the parent drug;6,8,11,12 however, microbiologic assays used in some published pharmacokinetic studies of cefotaxime actually measured total microbiologic activity since both cefotaxime and desacetylcefotaxime were active against the test organism.9,10,15,19,20,21,39,115,116,117 Information on body fluid and tissue concentrations of cefotaxime obtained from studies that used nonspecific microbiologic assays or from studies that did not identify the test organism used is reported as microbiologic activity in the following sections on the pharmacokinetics of the drug. More recent pharmacokinetic studies generally use high-performance liquid chromatography (HPLC) that differentiates between cefotaxime and desacetylcefotaxime and can specifically measure concentrations of cefotaxime and/or its metabolite.263,264,288,289,290

Absorption

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

Following IM administration of a single 500-mg or 1-g dose of cefotaxime in healthy adults with normal renal function, peak serum concentrations of the drug are attained within 30 minutes and average 11.7-11.9 mcg/mL and 20.5-25.3 mcg/mL, respectively.6,8,11 Plasma concentrations of cefotaxime are undetectable 8 hours after a single 500-mg IM dose of the drug but average 1 mcg/mL 8 hours after a single 1-g IM dose of the drug.6 In one multiple-dose study in adults with normal renal function receiving 500-mg doses of cefotaxime by IM injection every 8 hours, steady-state peak serum concentrations of cefotaxime ranged from 9.2-11.9 mcg/mL and steady-state trough serum concentrations of the drug ranged from 0.1-0.6 mcg/mL.8

In one study in healthy adults with normal renal function, a single 500-mg, 1-g, or 2-g dose of cefotaxime given by IV injection over 5 minutes resulted in serum concentrations of cefotaxime which averaged 37.9 mcg/mL, 102.4 mcg/mL, and 214.1 mcg/mL, respectively, immediately after the injection; serum concentrations of the drug averaged 1 mcg/mL, 1.9 mcg/mL, and 3.3 mcg/mL, respectively, 4 hours after the injection.8 In a multiple-dose study in healthy adults with normal renal function receiving 1-g doses of cefotaxime every 6 hours by IV infusion over 30 minutes, steady-state peak serum concentrations of cefotaxime ranged from 40.6-46 mcg/mL and steady-state trough serum concentrations of the drug ranged from 1.1-1.6 mcg/mL.8

Following a single cefotaxime dose of 50 mg/kg given by IV infusion over 10 minutes in average birthweight neonates 1-7 days of age, microbiologic activity in serum averaged 133 mcg/mL immediately after completion of the infusion, 85 mcg/mL 1 hour later, 52 mcg/mL 4 hours later, and 38 mcg/mL 6 hours later.

In one study in children 1 month to 12 years of age, serum concentrations of cefotaxime averaged 25.3 mcg/mL 30 minutes after a single cefotaxime dose of 25 mg/kg given by IM injection and averaged 53.3 mcg/mL 5 minutes after a single dose of 25 mg/kg of the drug given by IV injection.100

Distribution

Following IM or IV administration of usual dosages of cefotaxime, microbiologic activity is widely distributed into body tissues and fluids including the aqueous humor, bronchial secretions, sputum, middle ear effusions, bone,115 bile,115,116 and ascitic,117 pleural, and prostatic fluids.9 The apparent volume of distribution of cefotaxime in adults is reported to be 0.22-0.29 L/kg.10,13,14

Cefotaxime is 13-38% bound to serum proteins in vitro.2,6,11

Cefotaxime and its major metabolite are distributed into CSF following parenteral administration.263,264,288 Following IV administration of a single 2-g IV dose of cefotaxime in patients with uninflamed meninges, low concentrations of cefotaxime (0.14-1.81 mcg/mL) and desacetylcefotaxime (0.06-0.38 mcg/mL) are attained in CSF;288,290 however, higher concentrations are attained in patients with inflamed meninges.263,264,290 In one study in neonates and children 2 weeks to 2 years of age with inflamed meninges, IV injection or infusion over 30 minutes of cefotaxime doses of 50 mg/kg every 4-6 hours resulted in microbiologic activity in CSF which ranged from 1-13.2 mcg/mL 1-4 hours after administration. In another study in children 2 months to 12 years of age with meningitis who received cefotaxime in a dosage of 50 mg/kg IV every 6 hours, CSF concentrations of cefotaxime or its major metabolite averaged 6.2 or 5.6 mcg/mL, respectively, 1 hour after a dose; concurrent serum concentrations were 61.44 and 19.3 mcg/mL, respectively.264 In a study in adults with bacterial meningitis receiving 2 g of cefotaxime IV every 4 hours, trough CSF cefotaxime and desacetylcefotaxime concentrations ranged from 5.6-44.3 mcg/mL and 3.7-44 mcg/mL, respectively, after 1-3 days of therapy.

Following IM or IV administration of usual dosages of cefotaxime, microbiologic activity in hepatic bile is reported to be 15-75% of concurrent microbiologic activity in serum and microbiologic activity in gallbladder bile is reported to be up to 3 times greater than concurrent microbiologic activity in serum.115,116 Microbiologic activity in ascitic fluid is reported to be 40% of concurrent microbiologic activity in serum.117

In patients receiving 2-g doses of cefotaxime IV every 6 hours, concentrations of cefotaxime and desacetylcefotaxime in bronchial secretions averaged 1.7 and 5.8 mcg/mL, respectively, and plasma concentrations averaged 23.1 and 9.3 mcg/mL, respectively, in samples obtained 1-2 hours after the fourth dose.224

Cefotaxime readily crosses the placenta, and microbiologic activity in amniotic fluid is reported to be equal to or greater than concurrent microbiologic activity in maternal serum following multiple doses of the drug.21

Cefotaxime is distributed into milk.21 In one study, microbiologic activity in milk ranged from 0.25-0.52 mcg/mL 2-3 hours after a single 1-g IV dose of cefotaxime.21

Elimination

Cefotaxime is partially metabolized in the liver to desacetylcefotaxime which has antibacterial activity.2,7,14 (See Spectrum.) Desacetylation of cefotaxime occurs rapidly in vivo and rapidly in vitro in hemolyzed blood.2,18 Following IV injection over 5 minutes of a single 500-mg or 2-g dose of cefotaxime in adults with normal renal function, peak plasma concentrations of desacetylcefotaxime are generally attained within 45 minutes and average 2.7 mcg/mL and 9.8 mcg/mL, respectively.14 Desacetylcefotaxime is partially converted in the liver to desacetylcefotaxime lactone which is inactive and is further degraded to 2 unidentified inactive metabolites currently designated as UP₁ and its optical isomer UP₂.2,7,14,18

Serum concentrations of cefotaxime appear to decline in a biphasic manner.2,6,8,10,11,13,14,19 In adults with normal renal function, the serum half-life of cefotaxime in the initial phase (t_½α) averages 0.2-0.4 hours and the serum half-life of the drug in the terminal phase (t_½β) averages 0.9-1.7 hours.2,10,11,13,14,19 The t_½β of desacetylcefotaxime is longer than that of the parent drug and is reported to be 1.4-1.9 hours in adults with normal renal function.7,13,14 In adults with renal impairment, the t_½α of cefotaxime is not affected, and the t_½β is only slightly prolonged in patients with creatinine clearances of 20 mL/min or greater per 1.73 m².2,13,16 In adults with creatinine clearances of 10 mL/min or less per 1.73 m², the t_½β of cefotaxime is reported to range from 1.4-11.5 hours and the t_½β of desacetylcefotaxime is reported to range from 8.2-56.8 hours.13,16,19 The t_½β of both cefotaxime and desacetylcefotaxime may be prolonged in patients with impaired hepatic function.117,289 In a study in patients with chronic parenchymal liver disease with or without jaundice, edema, or ascites, the t_½β of the parent drug ranged from 1.49-2.42 hours and the apparent t_½ of the metabolite ranged from 7.1-13.4 hours.289

In one study in children 5 months to 1 year of age, the t_½α of cefotaxime averaged 0.2 hours and the t_½β averaged 1.2 hours.15 In children 2-12 years of age, the t_½α averaged 0.3 hours and the t_½β averaged 1.5 hours.15 In neonates, the half-life of cefotaxime depends principally on gestational and chronologic age.100 The t_½α is reported to range from 0.1-0.4 hours in premature or full-term neonates. The t_½β of cefotaxime averages 5-6 hours in premature neonates less than 1 week of age, 3.4-3.5 hours in premature neonates 1-4 weeks of age, 2-3.4 hours in full-term neonates less than 1 week of age, and 2 hours in full-term neonates 1-4 weeks of age.

Cefotaxime and its metabolites are excreted principally in urine; tubular secretion of the drug occurs.2,14 In adults with normal renal function, approximately 40-60% of a single IM or IV dose of cefotaxime is excreted in urine as unchanged drug and approximately 24% is excreted as desacetylcefotaxime within 24 hours. The majority of the IM or IV dose is excreted within the first 2 hours following administration. In one study, urine concentrations of cefotaxime ranged from 90-3261 mcg/mL in urine collected over 2 hours following a single 500-mg IM dose of cefotaxime.11

The serum clearance of cefotaxime in adults with normal renal function is reported to be 207-342 mL/minute per 1.73 m².8,11,19 In one study, the serum clearance of the drug averaged 23 mL/minute per 1.73 m² in low birthweight neonates 1-7 days of age and 44 mL/minute per 1.73 m² in average birthweight neonates 1-7 days of age.

Oral probenecid administered shortly before or concomitantly with cefotaxime usually slows the rate of excretion of the antibiotic and its metabolites and produces higher and more prolonged serum concentrations of cefotaxime and its metabolites. The volume of distribution of cefotaxime does not appear to be affected by concomitant administration of oral probenecid.

Cefotaxime and its metabolites are removed by hemodialysis.13,19 The amount of cefotaxime removed during hemodialysis depends on several factors (e.g., type of coil used, dialysis flow-rate); however, a 4- to 6-hour period of hemodialysis in one study removed into the dialysate 60% of a single 15 mg/kg dose of cefotaxime when the dose was given by IV injection immediately prior to dialysis.19 Only minimal amounts of cefotaxime are removed by peritoneal dialysis.13

Chemistry and Stability

Chemistry

Cefotaxime is a semisynthetic cephalosporin antibiotic. Like cefepime, ceftazidime, and ceftriaxone, cefotaxime is a parenteral aminothiazolyl cephalosporin.228,229 Cefotaxime contains an aminothiazolyl-acetyl side chain, with an α- syn -methoximino group, at position 7 of the cephalosporin nucleus. The aminothiazolyl side chain enhances antibacterial activity, particularly against Enterobacteriaceae, and generally results in enhanced stability against β-lactamases; the methoximino group contributes to stability against hydrolysis by many β-lactamases.

Cefotaxime is commercially available as the sodium salt. Potency of cefotaxime sodium is expressed in terms of cefotaxime. Cefotaxime sodium occurs as an off-white to pale yellow, crystalline powder.230 Cefotaxime sodium is sparingly soluble in water, slightly soluble in alcohol, and has a pK_a of 3.4. The sodium salt of cefotaxime contains approximately 50.5 mg (2.2 mEq) of sodium per gram of cefotaxime.230,366,367

Commercially available frozen premixed cefotaxime sodium injections containing 1 or 2 g of cefotaxime are sterile, nonpyrogenic, iso-osmotic solutions of the drug provided in a plastic container fabricated from specially formulated multilayered plastic (PL 2040).230 The 1- and 2-g frozen injections of cefotaxime contain approximately 1.7 g and 700 mg of dextrose hydrous, respectively, to adjust osmolality.230 The injections are buffered with sodium citrate hydrous and may contain hydrochloric acid and/or sodium hydroxide to adjust pH.230 After thawing, the injections are pale yellow to light amber solutions.230

Stability

Cefotaxime sodium powder for injection and solutions of the drug tend to darken, depending on storage conditions, and should be protected from excess heat and light.230,366,367 Discoloration of cefotaxime sodium sterile powder for injection or solutions of the drug may indicate a loss of potency.

Commercially available cefotaxime sodium sterile powder for injection should be stored at 15-30°C.230,366,367

Following reconstitution as directed by the manufacturer, cefotaxime sodium solutions containing 50-330 mg of cefotaxime per mL have a pH of 4.5-6.5 and are light yellow to amber in color.230 Following reconstitution with sterile or bacteriostatic water for injection, IM solutions containing 230-330 mg/mL are stable in their original containers for 12 hours at room temperature (22°C or lower) or 7 days when refrigerated (5°C or lower).230 Following reconstitution with sterile water for injection, IV solutions containing 50 or 95 mg/mL are stable for 24 hours at room temperature (22°C or lower) or 7 days when refrigerated (5°C or lower).230 When reconstituted as directed in 0.9% sodium chloride injection or 5% dextrose injection, solutions prepared from ADD-Vantage^® vials of the drug are stable for 24 hours at a room temperature of 22°C or less; these solutions should not be frozen.230

Cefotaxime sodium is physically and chemically compatible with the following IV solutions: 0.9% sodium chloride; 5% or 10% dextrose; 5% dextrose and 0.2%, 0.45%, or 0.9% sodium chloride; lactated Ringer's; ¼ M sodium lactate; 10% invert sugar; or Travasol^® 8.5%.230 Reconstituted solutions of cefotaxime sodium which have been further diluted with 50 mL to 1 liter of one of the above IV solutions are physically and chemically stable for 24 hours at room temperature or at least 5 days when refrigerated at 5°C or less.230 Cefotaxime sodium solutions are most stable at a pH of 5-7 and the drug should not be diluted with IV solutions (e.g., sodium bicarbonate) which have a pH greater than 7.5.230,366,367

Reconstituted solutions of cefotaxime sodium which have been further diluted with 50 mL to 1 liter of 0.9% sodium chloride injection or 5% dextrose injection may be frozen in Viaflex^® containers immediately after preparation and are stable for 13 weeks.230 Frozen solutions of cefotaxime sodium should be thawed at room temperature.230 Once thawed, solutions are stable for 24 hours at room temperature or 5 days at less than 5°C and should not be refrozen.230

The commercially available frozen premixed cefotaxime sodium injection should be stored at -20°C or lower.230 Thawed solutions of the commercially available frozen injection are stable for 24 hours at room temperature (22°C or lower) or 10 days when refrigerated at 5°C or lower.230 The commercially available frozen injection of the drug is provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy^® container).230 Solutions in contact with PL 2040 can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.230

Cefotaxime sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information. Because of the potential for incompatibility, cefotaxime sodium and aminoglycosides should not be admixed.230,366,367

Only references cited for selected revisions after 1984 are available electronically.

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