First-Generation Cephalosporin
Gram-positive bacteria: methicillin-susceptible Staphylococcus aureus (MSSA), coagulase –negative Staphylococci, penicillin-susceptible Streptococcus pneumoniae, Streptococci spp.
Gram-negative bacteria: Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
Cephalosporins exert bactericidal activity by interfering with the later stages of bacterial cell wall synthesis through inactivation of one or more penicillin-binding proteins and inhibiting cross-linking of the peptidoglycan structure. The cephalosporins are also thought to play a role in the activation of bacterical cell autolysins which may contribute to bacterial cell lysis.
Cephalosporins produce time-dependent killing.
Cmax: 188mcg/ml; Half-life: 1.8hours; Volume of distribution: 10L; Table 11
Hematologic: Hemolytic anemia, neutropenia, leukopenia, eosinophilia, thrombocytopenia, thrombocytosis, impaired platelet aggregation
Dermatologic: Rash (maculopapular), puritis, urticaria
Gastrointestinal: Diarrhea
Hepatic: Abnormal liver function tests
Renal: Interstitial nephitis
Other: Anaphylaxis
IV/IM: 500mg/10ml injection
1gram powder for reconstitution (IM)
Adult dose: 1-2g IV/IM q8h
Mild infections: 250-500 mg IV/IM q8h
Moderate to severe infections: 0.5-1 g IV/IM q6-8h
Severe, life-threatening infections: 1-1.5 g IV/IM q6h
Perinatal GBS disease, intrapartum prophylaxis: 2 g IV x 1 dose (started at time of labor or rupture of membranes) then 1 g IV q8h until delivery
Pre-operative use: 1 g IV/IM 0.5-1 hr prior to surgery, then 0.5-1 g IV/IM q6-8h x 24 hr
Urinary tract infections (uncomplicated): 1 g IV/IM q12h
50-100mg/kg/day, divided q6-8h, maximum of 6g per day
Renal failure: Renal failure: CrCl 35-54ml/min 0.5q q8h or 1g q12h
CrCl 11-34ml/min 0.5q q12h or 1g q24h
CrCl < 10ml/min 0.5q q18-24h
Hemodialysis: 0.5 to 1g IV post dialysis dose
Hepatic failure: No dosing changes recommended at this time.
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: Hypersensitivity to cephalosporins
Precautions: hypersensitivity to penicillins
Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine
Category B: No evidence of risk in humans but studies inadequate.
Therapeutic: Culture and sensitivities, serum levels, signs and symptoms of infection (e.g. fever, WBC)
Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, neutropenia and leukopenia