Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis
Yotsuji, A.; Mitsuyama, J.; Hori, R.; Yasuda, T.; Saikawa, I.; Inoue, M.; Mitsuhashi, S.
Antimicrobial Agents and Chemotherapy 32(12): 1848-1853
1988
ISSN/ISBN: 0066-4804 PMID: 3266730 Document Number: 312578
The susceptibilities of 52 clinical isolates of Bacteroides fragilis to five monoanionic cephalosporins were examined. Cefoperazone showed the highest antibacterial activity, following by ceftezole, cefazolin, cefamandole, and cephalothin. There were two groups of resistant strains; one group (ca. 15%), of which B. fragilis G-232 was a typical sample, was resistant to ceftezole (MIC, 100 .mu.g/ml), cefazolin (MIC, 100 .mu.g/ml), and cephalothin (MIC, 200 .mu.g/ml) but not cefoperazone (MIC, 6.25 .mu.g/ml) or cefamandole (MIC, 25 .mu.g/ml). On the basis of studies of stability to .beta.-lactamase, outer membrane permeation, and affinity for penicillin-binding proteins (PBPs), we conclude that decreased affinity for PBP 3 may play an important role in the resistance to ceftezole, cefazolin, and cephalothin in B. fragilis G-232. Another group (also ca. 15%), of which B. fragilis G-242 was a representative, was resistant to all five cephalosporins (MIC, 100 to 400 .mu.g/ml) and produced a high amount of .beta.-lactamase. Similar broad-spectrum resistance was seen in a mutant of strain G-232 that had a greater-than-30-fold increase in .beta.-lactamase production.