In vitro activity of N-formimidoyl thienamycin, moxalactam, and other new beta-lactam agents against Bacteroides fragilis: contribution of beta-lactamase to resistance

Abstract

N-Formimidoyl thienamycin (N-F-thienamycin) and moxalactam were compared with other currently available and investigational antibiotics against 100 clinical isolates of Bacteroides fragilis by an agar dilution method. N-F-thienamycin was the most active among the beta-lactam agents tested, with a minimal inhibitory concentration for 90% of isolates (MIC90) of 0.25 micrograms/ml. Moxalactam was next in activity, with an MIC90 of 4 micrograms/ml. N-F-thienamycin was somewhat more active, and moxalactam was slightly less active, than metronidazole and clindamycin. An increase in inoculum size caused an increase in the MIC of N-F-thienamycin, cefoperazone, and cefotaxime. This inoculum effect could influence the usefulness of these drugs in certain clinical conditions. The minimal bactericidal concentration was less than two times the MIC for most agents and less than four times the MIC for all beta-lactam agents at each inoculum size tested. Investigation of the mechanism of resistance to beta-lactam agents demonstrated a correlation between the level of resistance and beta-lactamase activity in each strain tested. N-F-thienamycin and cefoxitin were not hydrolyzed, and moxalactam was less susceptible to hydrolysis than the other beta-lactam antibiotics. Moxalactam and N-F-thienamycin may prove to be useful against infections with B. fragilis.