In Vitro Activity and Pharmacokinetics in Patients of Cefamandole, a New Cephalosporin Antibiotic

Abstract

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli , and Klebsiella pneumoniae . Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis . Both cefamandole and cefazolin were as active as cephalothin against S. aureus , were slightly more active against K. pneumoniae , and were considerably more active against E. coli . All strains of indole-positive Proteus sp. were inhibited by 6.3 μg of cefamandole per ml but only 20% were inhibited by 25 μg of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 μg of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 μg/ml in serum and levels ranged from 440 to 16,800 μg/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of ≥31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was ≥43%. The half-life of cefamandole in serum was 49 to 126 min.