The Activity of Cefotaxime and Desacetylcefotaxime Alone and in Combination Against Anaerobes and Staphylococci

Cefotaxime (CTX) and desacetylcefotaxime (des-CTX) alone and in combination were tested against anaerobic bacteria collected from clinical infections from several geographically diverse medical centers. The CTX minimum inhibitory concentration (MIC) inhibiting 50% of tested Bacteroides fragilis strains was in the moderately susceptible range (32 micrograms/ml), but when placed in combination with des-CTX it had a potency compatible to cefoxitin (MIC50, 8.0 micrograms/ml). Other B. fragilis group species (B. distasonis and B. vulgatus) were also susceptible to CTX and des-CTX alone at the MIC50 level. MIC90 statistics for CTX, cefoxitin, and ticarcillin were generally in the resistant range. Synergy studies showed that 80% of tested anaerobes were synergistically killed by the combination of CTX and des-CTX. Most of these strains had their synergy occur at drug levels that could be achieved in vivo. A large number of the B. thetaiotaomicron strains must be considered resistant to the combination because of the very high levels of des-CTX required to produce synergistic killing. Other drugs routinely used for anaerobic infections (clindamycin, chloramphenicol, and metronidazole) also had elevated B. thetaiotaomicron MICs. Endemic difference in susceptibility to the beta-lactam drugs were observed, especially the CTX-des-CTX combination. The combination and other beta-lactams were most usable for strains isolated from the Portland metropolitan area, were moderately active against those from Cleveland, and were rarely usable on Bacteroides isolates at Northwestern in Chicago. Laboratories are urged to monitor the cephalosporin and semisynthetic penicillin in vitro efficacy and not rely on published statistics. Staphylococcus aureus strains were susceptible to CTX alone, but were even more susceptible (two- to fourfold reduction in MICs) when used in combination with des-CTX. These data show CTX to be the most active antistaphylococcal compound among the new cephalosporins and to be comparable to cefamandole and cefuroxime, but superior to the anaerobe-active cefoxitin.