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We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of 264 Ug/lml. These isolates were also resistant to other beta-lactam antibiotics. Of 11 isolates, 4 were able to inactivate cefoxitin in broth cultures, as measured by microbiological and high-pressure liquid chromatography assays. Two distinct patterns of cefoxitin breakdown products were detected by high-pressure liquid chromatography analysis. The beta-lactamase inhibitors clavulanic acid and sulbactam failed to show synergism with cefoxitin. These data demonstrate that members of the B.fragilis group have acquired a novel resistance mechanism enabling them to inactivate cefoxitin.Cefoxitin possesses excellent in vitro activity against the Bacteroides fragilis group of organisms (20) and has been shown to be efficacious in the treatment of mixed aerobic and anaerobic infections involving these pathogens (21). The B. fragilis group, which includes: B. fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, and Bacteroides vulgatus, is resistant to many commonly used antimicrobial agents including penicillins and cephalosporins. Bacteroides uniformis has recently been considered with the B. fragilis group because of similar susceptibilities. These organisms are known to possess beta-lactamases which inactivate most of the first and second generation cephalosporins and penicillins (18,22). Of the currently available beta-lactam antibiotics, cefoxitin has the best in vitro activity (4,19). The enhanced activity of cefoxitin against these pathogens has been attributed to the resistance of the drug to the beta-lactamases of B. fragilis (3,5,7,11,22). Although there have been rare reports documenting the inactivation of the drug, the most common reported mechanism of cefoxitin resistance in this group of organisms has been the failure of the drug to penetrate through the outer membrane (6).Our laboratory has been the reference center for a multicenter study of the susceptibility of the B. fragilis group of organisms in the United States (19

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