Cefotetan  (PDF Version)

 

Antibiotic Class:

Second-Generation Cephalosporin (2nd generation cephamycin)

 

Antimicrobial Spectrum:

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp (less activity for Gram positives compared to 1st and 2nd generation cephalosporins), Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli Bacteroides spp.

 

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: 126-158 mcg/L; Protein binding: 90%; Half-life: 4.5 hours; Table 10

 

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: 1g, 2g, 10g

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

 

Dosing in adults:

Prophylaxis after Cesarean section: 1-2g IV as soon as umbilical cord is clamped

Surgical prophylaxis: 1-2g IV 0.5 to 1 hour prior to surgery

Bone and/or joint infection: 1-2g IV/IM q 12h

Lower respiratory tract infection: 1-2 g IV/IM q12h

 

Dosing in pediatrics:

40-60mg/kg/day divided q12h

Table 12

 

Disease state based dosing:

Renal failure:              CrCl > 30mL/min: Standard dose

                                 CrCl 10-30mL/min: 0.5g q12h OR 1-2g q24h

                                 CrCl < 10mL/min: 0.5g q24h OR 1-2g q48h

 

Hepatic failure:  No dosing changes recommended at this time.

 

Contraindications/Warnings/Precautions:

Contraindications:  Hypersensitivity to cephalosporins

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

Warnings: MTT side chain of cefotetan may interfere with the synthesis of vitamin K dependant clotting factors in the liver (may cause hypoprothrombinemia)

 

Drug Interactions:

Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine

Warfarin increased risk of bleeding

 

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. Cefotetan may cause hypoprothrombinemia (See Warnings)

 

Brand names/Manufacturer:

Cefotan /AstraZeneca