Cefazolin, a new semisynthetic cephalosporin antibiotic. II

Abstract

Cefazolin is a new antibiotic derived from 7-aminocephalosporanic acid, having the structure of 7-[1-(1H)-tetrazolylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-Δ3-cephem-4-carboxylic acid. This substance is a broad-spectrum antibiotic, active in vitro against most of Gram-positive and Gram-negative species of bacteria except for Ps. aeruginosa, and is also active against penicillinase-producing strains of Staph. aureus. The activity of cefazolin against fresh isolates of E. coli and Kl. pneumoniae seems superior to those of other antibiotics used in this study. The in vitro activity of cefazolin is little influenced by size of inoculum, presence of rabbit serum, or kinds or properties of test medium. The activity of cefazolin is apparently bactericidal against both Gram-positive and Gram-negative bacteria at or above the MIC levels. In experiments on the development of resistance in vitro, the MICs of cefazolin against Staph. aureus strain 209 P and E. coli strain NIHJ increase slowly in a stepwise over a period of 17 transfers. The rate of resistance development of cefazolin is comparable with that of cepholoridine or ampicillin. Cefazolin is relatively stable to enzymes from Staph. aureus and E. coli, which readily inactivate ampicillin and benzyl penicillin. Cefazolin is not remarkably degraded by the tissue homogenates of rat, although cephalothin is degraded quite rapidly. Cefazolin, in the single subcutaneous dose, shows excellent protecting activity against experimental infections in mice infected with both PC-sensitive and resistant strains of Staph. aureus, and is also fairly effective against infections in mice with Diplococcus pneumoniae, E. coli and Proteus mirabilis. © 1970, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.