Synergistic antibacterial interaction of cefotaxime and desacetylcefotaxime.

Cefotaxime (CTX) is metabolized in desacetylcefotaxime (dCTX), a less potent compound which shows, however, a higher stability against selected beta-lactamases produced by Gram-negative organisms. The aim of this study was to verify if the antimicrobial activity of CTX against 260 clinical aerobic and anaerobic pathogens isolated in our institution was enhanced by its metabolic derivative dCTX. The combination of CTX and dCTX, assessed by checkerboard titration, was completely or partially synergistic towards 61% of the 220 aerobic organisms tested and against 68% of the 40 Bacteroides strains analyzed. In addition we have investigated, by the time-kill method, the in-vitro interactions against 50 aerobic strains of CTX and dCTX alone and in combination with netilmicin, a drug often employed in severe infections in combination with beta-lactam agents in order to provide effective killing of resistant nosocomial pathogens. Time-kill studies indicated that 36% of the aerobic nosocomial strains were synergistically inhibited by the combination of CTX/dCTX with netilmicin. These results indicate that dCTX makes an important contribution to the clinical efficacy of CTX.