Dosing

Dosing: Adult
Arthritis (septic): I.V.: 1 g every 8 hours
Brain abscess and meningitis: I.V.: 2 g every 4-6 hours
C-section: 1 g as soon as the umbilical cord is clamped, then 1 g I.M., I.V. at 6- and 12-hours intervals
Epiglottitis: I.V.: 2 g every 4-8 hours
Gonorrhea: I.M.: 1 g as a single dose; disseminated 1 g every 8 hours
Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (in combination with metronidazole): I.V.: 1-2 g every 6 -8 hours for 4-7 days (provided source controlled)
Life-threatening infections: I.V.: 2 g every 4 hours
Liver abscess: I.V.: 1-2 g every 6 hours
Lyme disease:
Cardiac manifestations: I.V.: 2 g every 4 hours
CNS manifestations: I.V.: 2 g every 8 hours for 14-28 days
Moderate/severe infections: I.M., I.V.: 1-2 g every 8 hours
Orbital cellulitis: I.V.: 2 g every 4 hours
Peritonitis (spontaneous): I.V.: 2 g every 8 hours, unless life-threatening then 2 g every 4 hours
Septicemia: I.V.: 2 g every 6-8 hours
Skin and soft tissue:
Mixed, necrotizing: I.V.: 2 g every 6 hours, with metronidazole or clindamycin
Bite wounds (animal): I.V.: 2 g every 6 hours
Surgical prophylaxis: I.M., I.V.: 1 g 30-90 minutes before surgery
Uncomplicated infections: I.M., I.V.: 1 g every 12 hours

Dosing: Pediatric
Infants and Children 1 month to 12 years:
Susceptible infections: I.M., I.V.: Infants and Children 1 month to 12 years: <50 kg: 50-200 mg/kg/day in divided doses every 6-8 hours
Epiglottitis: I.M., I.V.: 150-200 mg/kg/day in 4 divided doses with clindamycin for 7-10 days
Meningitis: I.M., I.V.: 200 mg/kg/day in divided doses every 6 hours
Pneumonia: I.V.: 200 mg/kg/day divided every 8 hours
Sepsis: I.V.: 150 mg/kg/day divided every 8 hours
Typhoid fever: I.M., I.V.: 150-200 mg/kg/day in 3-4 divided doses (maximum: 12 g/day); fluoroquinolone resistant: 80 mg/kg/day in 3-4 divided doses (maximum: 12 g/day)
Children >12 years: Refer to adult dosing.

Dosing: Geriatric
Refer to adult dosing.

Dosing: Renal Impairment
Clcr 10-50 mL/minute: Administer every 8-12 hours.
Clcr <10 mL/minute: Administer every 24 hours.

Dosing: Hepatic Impairment
Dosage reduction generally not necessary unless concurrent severe renal impairment. Consider dose reduction to 0.5 g every 12 hours in patients with Clcr <5 mL/minute (Wise, 1985).

Use

Treatment of susceptible infection in respiratory tract, skin and skin structure, bone and joint, urinary tract, gynecologic as well as septicemia, and documented or suspected meningitis. Active against most gram-negative bacilli (not Pseudomonas) and gram-positive cocci (not enterococcus). Active against many penicillin-resistant pneumococci.

Adverse Reactions

1% to 10%:
Dermatologic: Rash, pruritus
Gastrointestinal: Diarrhea, nausea, vomiting, colitis
Local: Pain at injection site
<1% (Limited to important or life-threatening): Anaphylaxis, arrhythmia (after rapid I.V. injection via central catheter), BUN increased, candidiasis, creatinine increased, eosinophilia, erythema multiforme, fever, headache, interstitial nephritis, neutropenia, phlebitis, pseudomembranous colitis, Stevens-Johnson syndrome, thrombocytopenia, transaminases increased, toxic epidermal necrolysis, urticaria, vaginitis
Reactions reported with other cephalosporins: Agranulocytosis, aplastic anemia, cholestasis, hemolytic anemia, hemorrhage, pancytopenia, renal dysfunction, seizure, superinfection, toxic nephropathy.

Contraindications

Hypersensitivity to cefotaxime, any component of the formulation, or other cephalosporins

Warnings / Precautions Drug

Concerns related to adverse effects:
• Arrhythmia: A potentially life-threatening arrhythmia has been reported in patients who received a rapid bolus injection via central line.
• Granulocytopenia: Granulocytopenia and more rarely agranulocytosis may develop during prolonged treatment (>10 days).
• Penicillin allergy: Use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tissue inflammation: Minimize tissue inflammation by changing infusion sites when needed.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; modify dosage in severe impairment.

Interactions

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification

Pregnancy

B
Pregnancy Implications
Teratogenic effects were not observed in animal studies; therefore, cefotaxime is classified as pregnancy category B. Cefotaxime crosses the placenta and can be found in fetal tissue. An increased risk of teratogenic effects has not been observed following maternal use. During pregnancy, peak cefotaxime serum concentrations are decreased and the serum half-life is shorter.

Lactation

Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Very small amounts of cefotaxime are excreted in breast milk. The manufacturer recommends that caution be exercised when administering cefotaxime to nursing women. Nondose-related effects could include modification of bowel flora. The pregnancy-related changes in cefotaxime pharmacokinetics continue into the early postpartum period.

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics / Kinetics

Distribution: Widely to body tissues and fluids including aqueous humor, ascitic and prostatic fluids, bone; penetrates CSF best when meninges are inflamed
Metabolism: Partially hepatic to active metabolite, desacetylcefotaxime
Half-life elimination:
Cefotaxime: Premature neonates <1 week: 5-6 hours; Full-term neonates <1 week: 2-3.4 hours; Adults: 1-1.5 hours; prolonged with renal and/or hepatic impairment
Desacetylcefotaxime: 1.5-1.9 hours; prolonged with renal impairment
Time to peak, serum: I.M.: Within 30 minutes
Excretion: Urine (as unchanged drug and metabolites)