Comparative antibacterial activities of 7 alpha-methoxy cephalosporins and 7 beta-methoxyiminoacetamido cephalosporins against Bacteroides fragilis

Abstract

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...

The cephalosporin antimicrobial agents: a comprehensive review

“…T h e in vitro activities of the various cephalosporins are compared in Tables 11, 111, and IV. These tables were generated from reports of in vitro susceptibility from a variety of geographic areas and practice settings (Ryan et al, 1976;Shadomy et al, 1977;Silver et al, 1977;Hirsh & Smith, 1978;Jones et al, 1979;Preston, 1979;Angehrn et al, 1980;Brogden et al, 1981;Jones et al, 1981;Phillips, el al., 1981;Barry et al, 1982;Bauernfeind, 1983;Jones & Barry, 1983;Neu, 1983;Phillips et al, 1983;Kesado et al, 1984;Adamson et al, 1985;Richards & Brogden, 1985;Richards & Heel, 1985;Wilson et al, 1985;Saltiel & Brogden, 1986;Cox, 1987). The scale used is based upon the usual minimum inhibitory concentrations reported for 90% of the tested isolates (MICyo), however, rather than list the numerical ranges, activity is expressed in comparative terms in order to amplify the similarities and the differences which exist among these cornpounds in terms of clinically useful antibacterial spectrum.…”

National Committee for Clinical Laboratory Standards agar dilution susceptibility testing of anaerobic gram-negative bacteria

“…Some of the molecular modifications include the 7a-methoxy cephalosporins like cefoxitin, moxalactam, and cefotetan and the 7,B-methoxyiminoacetamide cephalosporin group represented by cefotaxime and cefmenoxime. These and related drugs have been evaluated for in vitro activity against Bacteroides species, particularly the bile-resistant group (1,6,9,13,20,29,34). Each of these studies examined a few antibiotics, but none tested the large number of drugs included in this report.…”

In vitro activity of cefbuperazone compared with that of other new beta-lactam agents against anaerobic gram-negative bacilli and contribution of beta-lactamase to resistance

“…These same organisms were able to hydrolyze other ,-lactam agents used in this study except for cefotetan and cefoxitin. Cefbuperazone, cefotetan, and cefoxitin are cephamycins with a 7a-inethoxy substituent which seems important in Bacteroides P-lactamase resistance (4,8).…”