The in vitro antibacterial activities of the newly developed 7a-methoxy cephalosporins and 7I-methoxyiminoacetamido cephalosporins against 67 clinical isolates of Bacteroides fragilis and their resistance to the hydrolytic action of a ,-lactamase produced by B. fragilis were simultaneously compared. The minimal inhibitory concentrations that inhibited 90% of the 7a-methoxy cephalosporins, cefoxitin, cefmetazole, moxalactam, and cefotetan, against the isolates were 4, 8, 8, and 16 jig/ml, respectively, and these antibiotics were entirely resistant to hydrolysis by ,-lactamases (0.10 ,umol/h per mg of protein) of the isolates. By contrast, 7p-methoxyiminoacetamido cephalosporins represented by cefotaxime, ceftizoxime, and cefmenoxime were not effective, as indicated by the minimal inhibitory concentrations that inhibited 90%, 64, 32, and 128 ,ug/ml, respectively. Their antibacterial activities clearly corresponded to their resistance to the hydrolytic action of the P-lactamase: namely, the correlation coefficients in regression curves of cefotaxime, ceftizoxime, and cefmenoxime, which were expressed by the antibacterial activity (x axis) and the ,-lactamase activity (y axis) were 0.098, 0.034, and 0.163, respectively.In recent years, anaerobic bacteria, especially Bacteroides fragilis, have been isolated from clinical specimens with increasing frequency (6,8). Several investigators have reported that B. fragilis strains produce a ,B-lactamase which has cephalosporinase activity and that it plays a significant role in the resistance of these organisms to B-lactam compounds (2,11,13,17,22). On the other hand, several newlactam compounds have been developed in recent years for the treatment of infections caused by resistant organisms which produce a ,-lactamase (1,7,9,20). Prominent among such compounds are cefoxitin, cefmetazole, moxalactam, and cefotetan, which are grouped as 7a-methoxy cephalosporins, and cefotaxime, ceftizoxime, and cefmenoxime, which are included in the 7p-methoxyiminoacetamido cephalosporin group. Both groups are currently in clinical use. The present study was undertaken to compare the in vitro antibacterial activities of 7a-methoxy cephalosporins and 7,3-methoxyiminoacetamido cephalosporins against 67 clinical isolates of B. fragilis and to investigate whether there exists a correlation between their antibacterial activity and the resistance to the hydrolytic action of ,B-lactamases produced by B. fragilis.
MATERIALS AND METHODSOrganisms. All of the 67 B. fragilis isolates tested were obtained from clinical specimens and were identified at the Institute of Anaerobic Bacteriology, Gifu University School of Medicine, Japan, according to the criteria of the Virginia Polytechnic Institute Anaerobe Laboratory Manual (21). Organisms were maintained at room temperature in tubes containing GAM semisolid medium (1% peptone, 0.3% soya peptone, 1% proteose peptone, 1.35% serum digest powder, 0.5% yeast extract, 0.22% beef extract powder, 0.12% liver extract powder, 0.3% glucose, 0.25% potassium dehydro...