A reassessment of the activity of the third-generation cephalosporins against anaerobes and Staphylococcus aureus

Abstract

The in vitro activity of cefotaxime (CTX) alone and in combination with its metabolite desacetylcefotaxime (dCTX) was evaluated against 106 isolates of Bacteroides species. and 32 strains of Staphylococcus aureus. All strains were recovered from infected tissues of diabetic patients. Addition of dCTX to the parent compound markedly increased the inhibitory activity against Bacteroides species in general and Bacteroides fragilis and Bacteroides vulgatus in particular. No effect of the combination of both agents on Bacteroides thetaiotaomicron or Bacteroides ovatus was observed; 50% of B. fragilis infections were susceptible to CTX alone and 81% became susceptible to CTX plus dCTX. In addition, a partial synergistic interaction against 20 strains of B. fragilis resulted in a four- to nine-fold reduction in the minimal inhibitory concentration (MIC) after dCTX was added to CTX. Interestingly, 10 of 20 strains that exhibited an MIC of 64-128 micrograms/mL with CTX alone became very susceptible after the combination of parent and metabolite. This favorable positive interaction of both agents was also observed with S. aureus; a two- to four-fold reduction in MIC values was observed when dCTX was added.