In vitro antimicrobial activity evaluation of cefodizime (HR221), a new semisynthetic cephalosporin

Abstract

Cefodizime (HR221) is a new alpha-methoxyimino cephalosporin developed by Hoechst-Roussel with a reported serum half-life of over 2 h. In vitro susceptibility studies showed that the cefodizime spectrum includes all those Enterobacteriaceae, staphylococci, Streptococcus spp., Haemophilus spp., and Neisseria spp. normally susceptible to cefotaxime (HR756) or ceftizoxime (FK749) or both. Cefodizime was less active (two- to eightfold) than cefotaxime or ceftizoxime against some enteric species, but was the most potent drug against some strains of Morganella spp. and Proteus vulgaris. Enterococci, methicillin-resistant Staphylococcus aureus, and most Pseudomonas spp. were resistant to cefodizime (median minimum inhibitory concentrations, greater than or equal to 64 microgram/ml). Acinetobacter spp. and Pseudomonas aeruginosa strains required cefodizime concentrations of 32 microgram/ml to inhibit 50% of tested strains. Cefodizime was very stable to hydrolysis by Richmond-Sykes type I, II, III, and IV beta-lactamases, as well as the enzyme derived from Bacillus cereus. The reference PADAC and nitrocefin substrate hydrolysis by a type I beta-lactamase was markedly inhibited (greater than 80%) by cefodizime at concentrations 0.4 to 4% of substrate concentration. Cefodizime was active against 43% of bacteria which were resistant to cephalothin and cefamandole and against 58% of those resistant to aminoglycosides.