Cefazolin  (PDF Version)

Antibiotic Class:

First-Generation Cephalosporin

Antimicrobial Spectrum:

Gram-positive bacteria:  methicillin-susceptible Staphylococcus aureus (MSSA), coagulase ľnegative Staphylococci, penicillin-susceptible Streptococcus pneumoniae, Streptococci spp.

Gram-negative bacteria:  Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis

Mechanism of Action:

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.

Pharmacodynamics:

Cephalosporins produce time-dependent killing.

Pharmacokinetics:

Cmax: 188mcg/ml; Half-life: 1.8hours; Volume of distribution: 10L; Table 11

Adverse Effects:

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

Dosage:

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

Pediatric dose (1 month and older):

50-100mg/kg/day, divided q6-8h, maximum of 6g per day

Disease state based dosing:

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.

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:

Contraindications:  Hypersensitivity to cephalosporins

Precautions: hypersensitivity to penicillins

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 (e.g. fever, WBC)

Toxic:  Urinalysis, BUN, SCr, AST and ALT, skin rash, neutropenia and leukopenia

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