Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group

Abstract

Clavulanic acid reduced the MICs of amoxicillin, carbenicillin, cefamandole, cefotaxime, ceftazidime, ceftizoxime, cephalothin, and penicillin G, but not of cefoxitin or moxalactam, against 77 isolates of the Bacteroidesfragilis group, all rapidly P-lactamase positive by the nitrocefin slide test. It had no effect on the susceptibilities of eight Bacteroides distasonis strains that were slowly P-lactamase positive (18 h of incubation).The production of P-lactamase by different species of the Bacteroidesfragilis group is a major factor in their resistance to ,-lactam agents (18). Recently, new 1-lactam antibiotics resistant to hydrolysis by f-lactamase have been introduced (17). Many of these agents, such as ceftizoxime (6, 9) and moxalactam (8), are active against B. fragilis, but other members of the B. fragilis group, especially those producing indole, are much more resistant (12,13,15,20

Inactivation of cefoxitin and moxalactam by Bacteroides bivius beta-lactamase

“…Their identification was confirmed by the methods described in the Anaerobe Laboratory Manual (14). All strains were ,-lactamase positive within 2 min in a nitrocefin (Glaxo Pharmaceuticals, Ltd., Greenford, England) microwell test (17). Crude P-lactamase extracts were obtained by ultrasonic treatment and differential ultracentrifugation, as previously described (16).…”

“…Both species produce a ,-lactamase which may play an important role in their resistance to P-lactams (15,16,25,32,37). Moxalactam and cefoxitin are known to be resistant to the ,B-lactamases generally found in B. fragilis (10,11,27,30,37), and there is little or no effect for clavulanic acid, a ,B-lactamase inhibitor, on the susceptibility of B. fragilis to cefoxitin (17,39,41), although some effect on the inhibitory activity of moxalactam in some resistant strains was reported recently (41). We reported previously that for P-lactamase-positive strains of B. bivius, there is a potentiating effect of clavulanic acid on their susceptibilities to cefoxitin and moxalactam which correlates with the amount of ,-lactamase produced (16).…”

Effect of beta-lactamase inhibitors on the activities of various beta-lactam agents against anaerobic bacteria

“…Various ,-lactamase inhibitors have been used in recent years and generally improve the susceptibilities of ,-lactamase-producing anaerobes (2,4,7,15,16). This report represents a compilation of several studies undertaken over the past 2 years at the Veterans Administration Wadsworth Medical Center Microbial Diseases Research Laboratory.…”

Comparison of the inoculum effect of cefoxitin and other cephalosporins and of beta-lactamase inhibitors and their penicillin-derived components on the Bacteroides fragilis group

“…Sutter et al (21) have suggested that both large and small inocula should be used to detect resistance of anaerobic bacteria to beta-lactam agents. In a recent review on the inoculum effect, Brook (7) summarized the laboratory experience to date with B. fragilis group species and noted that while some of the cephalosporins had been studied, there was scant data on the P-lactamase inhibitor combinations and their penicillin-derived components (1,3,17,18). It seems important to evaluate the 1-lactamase inhibitor combinations since these compounds are used in clinical situations where B. fragilis group species are 'potential pathogens and an increased density' of inoculum might cause increased enzymatic destruction.…”

“…Sutter et al (21) have suggested that both large and small inocula should be used to detect resistance of anaerobic bacteria to beta-lactam agents. In a recent review on the inoculum effect, Brook (7) summarized the laboratory experience to date with B. fragilis group species and noted that while some of the cephalosporins had been studied, there was scant data on the P-lactamase inhibitor combinations and their penicillin-derived components (1,3,17,18 …”