Cephradine

Antibiotic Class:

First-Generation Cephalosporin

Antimicrobial Spectrum:

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

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:

500mg dose; Cmax: 17.7mcg/ml; Half-life: 0.6hours; Protein-binding: 10-20%; Table 10

Adverse Effects:

Hematologic: 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:

PO: 250mg, 500mg capsule

       250mg/5ml powder for reconstitution (suspension)

Adult dose:

0.5-1g PO q6-12h

Respiratory tract infection: 250mg PO q6h or 500mg PO q12h;

Pneumonia, 500mg PO q6h or 1g PO q12h

Skin/skin structure infection: 250mg PO q6h or 500 mg PO q12h

Urinary tract infection (uncomplicated)L 500 mg PO q12h

(serious) 500 mg PO q6h

(severe or chronic) up to 1 g PO q6h

Pediatric dose:

75-100mg/kg/d, divided q6-12h

Otitis media: 25-50 mg/kg/day PO divided q6-12h;

(due to H. influenzae): 75-100 mg/kg/day PO divided q6-12h - maximum 4g per day

Disease state based dosing:

Renal failure:              CrCl 10-50 mL/min, 50% of usual dose at normal interval

                                 CrCl less than 10 mL/min, 25% of usual dose at normal interval

Hepatic failure:  No dosing changes recommended at this time.

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

Brand names/Manufacturer: