Inactivation of cefuroxime and cefotaxime by Bacteroides fragilis in vitro, and its influence on the treatment of an experimental Escherichia coli/Bacteroides fragilis mixed infection.
The activity of amoxycillin/clavulanic acid was compared with that of cefuroxime and cefotaxime, alone and combined with metronidazole, in preventing the development of infections in the mouse caused by subcutaneous injection of a beta-lactamase-producing strain, Escherichia coli E96, or a mixed inoculum of E. coli E96 and Bacteroides fragilis VPI 8908. Amoxycillin/clavulanic acid, cefuroxime and cefotaxime were equally efficacious in preventing development of the E. coli E96 monoinfection at clinically achievable concentrations. However, the activity of cefuroxime against E. coli E96 in the mixed infection was markedly reduced as was, to a lesser extent, that of cefotaxime. Co-administration of metronidazole improved slightly the activity of cefuroxime against E. coli E96 in the mixed infection, but had no such enhancing effect on cefotaxime. In contrast, amoxycillin/clavulanic acid effectively prevented development of the mixed infection in all treated mice. Results of in-vitro studies showed that cefuroxime and cefotaxime were stable in a culture of E. coli E96, and were rapidly bactericidal against this strain. In contrast, both cephalosporins were hydrolysed in a mixed culture of E. coli E96/Bact. fragilis VPI 8908, which resulted in diminished bactericidal activity, particularly of cefuroxime, which was not restored by addition of metronidazole. Amoxycillin/clavulanic acid was stable in the mixed culture and caused a significant reduction in numbers of both organisms. These in-vitro data explain the findings of the in-vivo studies, and establish that the beta-lactamase activity of Bact. fragilis VPI 8908 was responsible for the diminished activity of cefuroxime and cefotaxime, combined with metronidazole, against a mixed E. coli/Bact. fragilis infection.
Beale
A S
AS
Beecham Pharmaceuticals Research Division, Surrey.
Gisby
J
J
D000658:Amoxicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001442:Bacteroides Infections / Q000150:complications / Q000378:metabolism* / Q000382:microbiology; D001441:Bacteroides fragilis / Q000378:metabolism*; D002439:Cefotaxime / Q000378:metabolism* / Q000627:therapeutic use; D002444:Cefuroxime / Q000378:metabolism* / Q000627:therapeutic use; D002511:Cephalosporins / Q000378:metabolism*; D002969:Clavulanic Acids / Q000494:pharmacology / Q000627:therapeutic use; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000150:complications / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D008795:Metronidazole / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism
D002511:Cephalosporins; D002969:Clavulanic Acids; D008795:Metronidazole; D000658:Amoxicillin; D001618:beta-Lactamases; D002439:Cefotaxime; D002444:Cefuroxime