In vitro experience with cefonicid.

Cefonicid was found to be highly active in vitro against greater than 5,000 bacterial isolates. Its spectrum of activity was similar to that observed with cefamandole, including both gram-positive and gram-negative pathogens. No significant activity was observed against methicillin-resistant staphylococci, enterococci, Pseudomonas, Serratia, Acinetobacter, and Bacteroides species. Studies in which susceptibility disks containing 30 micrograms of cefonicid, cefamandole, or cephalothin were used and zone sizes were plotted against MIC values resulted in similar regression lines. Interpretive breakpoints were less than or equal to 14 mm for defining resistance and greater than or equal to 18 mm for defining susceptibility. The results for isolates tested with cefonicid susceptibility disks were highly predictive of clinical efficacy. On the basis of the observed pharmacokinetics of cefonicid at the usual single daily dose of 1 g, a bacterial strain is considered susceptible if the MIC values are not greater than 16 micrograms/ml. Organisms with MICs greater than 32 micrograms/ml are considered resistant. The profile of the stability of cefonicid to hydrolysis by beta-lactamases is similar to that observed with cefamandole. The affinity of cefonicid to the penicillin-binding proteins of Escherichia coli also resembled that of cefamandole, with its greatest affinity for penicillin-binding proteins 1a, 3, and 1b, in that order.