Second-Generation Cephalosporin (2nd generation cephamycin)
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.
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.
Cephalosporins exhibit time-dependent killing (T > MIC)
Dose of 1g: Cmax: 126-158 mcg/L; Protein binding: 90%; Half-life: 4.5 hours; Table 10
Hypersensitivity: Maculopapular rash, Urticaria, Pruritis, Anaphylaxis/angioedema, eosinophilia
Hematologic: Hypoprothrombinemia, Neutropenia, Leukopenia, Thrombocytopenia
GI: Diarrhea, C. difficile disease
Renal: Interstitial nephritis
IV: Powder for reconstitution: 1g, 2g, 10g
Intravenous Solution: 1gm/50mL, 2g/50mL
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
40-60mg/kg/day divided q12h
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: 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)
Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine
Warfarin – increased risk of bleeding
Category B: No evidence of risk in humans but studies inadequate.
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)