Cefotetan, a new cephamycin: comparison of in vitro antimicrobial activity with other cephems, beta-lactamase stability, and preliminary recommendations for disk diffusion testing

Abstract

Cefotetan is a new, potent, 7 alpha-methoxy cephalosporin (cephamycin). The in vitro activity of cefotetan tested in a multiphasic, collaborative study against 12,260 consecutive clinical isolates and 448 selected isolates showed 93% of Enterobacteriaceae, 90% of methicillin-susceptible Staphylococcus aureus (broth dilution), 83% of Bacteroides fragilis, and 72% of non-enterococcal streptococci to be inhibited by less than or equal to 8 micrograms/ml. Beta-Lactamase-producing and -nonproducing Haemophilus influenzae strains were inhibited by less than or equal to 1.0 micrograms/ml. Cefotetan's inhibitory spectrum paralleled those of the newest generation of cephems and exceeded those of cefoxitin and cefamandole. No useful activity was present against Streptococcus faecalis or Pseudomonas aeruginosa. Cefotetan was bactericidal without significant inoculum effect and was highly resistant to hydrolysis by Richmond-Sykes types I, III, and IV beta-lactamases. Hydrolysis of the chromogenic cephalosporin PADAC (pyridine-2-azo-p-dimethylaniline cephalosporin) by type I beta-lactamases was markedly inhibited by concentrations of cefotetan similar to those of the potent inhibitor dicloxacillin. Analysis of agar disk diffusion for several disk potencies and broth dilution susceptibility tests by regression and error rate-bounding methods produced preliminary tentative zone standards (30-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 8 micrograms/ml susceptible and greater than 32 micrograms/ml resistant, or 75-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 16 micrograms/ml susceptible and greater than or equal to 64 micrograms/ml resistant) of greater than or equal to 18 mm susceptible, less than or equal to 14 mm resistant, and 15 to 17 mm indeterminate. Staphylococcus aureus testing with the 30-micrograms disk is not recommended.