Comparison of the in vitro action and interaction of cefotaxime and desacetylcefotaxime against clinical isolates of Bacteroides spp.

Abstract

Desacetylcefotaxime (dCTX), the in vivo metabolite of cefotaxime (CTX), possess significant in vitro antimicrobial activity similar to the parent compound against a variety of aerobic and anaerobic bacteria. In vitro susceptibility studies showed that CTX inhibited 86% of 473 strains of the Bacteroides fragilis at a concentration of 32 micrograms/ml while dCTX inhibited 91% of the test isolates at the same concentration. Strains of the B. fragilis species were significantly more susceptible to CTX than were the non-B. fragilis species. Susceptibility testing of CTX and dCTX in a 1:1 ratio produced significantly more inhibitory activity, especially against the non-B. fragilis strains. Synergy studies showed that the interaction of CTX and dCTX was either completely or partially synergistic against 85% of 92 test organisms. The presence of dCTX was also shown to lower the CTX MIC values four-fold or greater in 82% of the synergy studies. Synergy was noted against strains of the B. fragilis group, B. melaninogenicus group, B. bivius, B. disiens, and B. capillosus. Through the use of time-kill kinetics studies, the interaction of CTX and dCTX was shown to be additive at subinhibitory and inhibitory concentrations and suggestedly synergistic at suprainhibitory concentrations against strains of the B. fragilis group. These in vitro studies demonstrate that dCTX increases the inhibitory and bactericidal activity of CTX when tested in combination.