Cefotaxime  (PDF Version)

Antibiotic Class:

Third-Generation Cephalosporin

Antimicrobial Spectrum:

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli

Mechanism of Action:

Cephalosporins exert bactericidal activity by interfering with bacterial cell wall synthesis and inhibiting cross-linking of the peptidoglycan. The cephalosporins are also thought to play a role in the activation of bacterical cell autolysins which may contribute to bacterial cell lysis.

Pharmacodynamics:

Cephalosporins exhibit time-dependent killing (T > MIC)

Pharmacokinetics:

Dose of 1g: Cmax: 102 mcg/L; Half-life: 1.1 hours; Volume of distribution: 14L; Table 11

Adverse Effects:

Hypersensitivity: Maculopapular rash, Urticaria, Pruritis, Anaphylaxis/angioedema, eosinophilia

Hematologic: Hypoprothrombinemia, Neutropenia, Leukopenia, Thrombocytopenia

GI: Diarrhea, C. difficile disease

Renal: Interstitial nephritis

Table 14

Dosage:

IV: Powder for reconstitution: 500mg, 1g, 2g, 10g, 20g

      Intravenous Solution: 1g/50mL, 2 g/50mL

Dosing in adults:

Meningitis: 1-2 g IV/IM q8h

Bone and/or joint infection: 1-2g IV/IM q8h

Gonococcal urethritis: 0.5g IM x 1 dose

Lower respiratory tract infection: 1-2 g IV/IM q8h

Bacterial peritonitis: 1-2g q8-12h

Dosing in pediatrics:

100-150mg/kd/day divided q4-6h

Table 12

Disease state based dosing:

Renal failure:  CrCl > 50mL/min: Standard dosing

                       CrCl 10-50mL: 1-2g q8-12h

                       CrCl < 10mL/min 1-2g q24h    

Hepatic failure:  No dosing changes recommended at this time.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 1-2g IV q12h

CVVHD (Continuous venovenous hemodialysis): 2g IV q12h

CVVHDF (Continuous venovenous hemodiafiltration) 2g IV q12h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions:  hypersensitivity to penicillins, history of gastrointestinal disease, particularly colitis, renal impairment

Drug Interactions:

Live Typhoid Vaccine: decreased immunological response to the typhoid vaccine

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, Neutropenia and leukopenia, Prothrombin time in patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy.

Brand names/Manufacturer:  Cefotaxime /American Pharmaceuticals; Claforan /Aventis