Induction of beta-lactamase by cefoxitin in anaerobic intestinal microflora

Beta-lactamases produced by two anaerobic bacterial strains, Bacteroides ovatus Ax34:1 and Clostridium butyricum NBL3, were shown to be significantly inducible under anaerobic conditions in subinhibitory concentrations of cefoxitin. The induction ratio of beta-lactamase production for Bacteroides ovatus was 2.6 and for Clostridium butyricum 1.6. Incubation of faecal samples with different concentrations of cefoxitin did not result in any induction of beta-lactamase production. When adding a highly inducible aerobic strain (Citrobacter freundii F72:6, induction ratio of 26.5 in broth culture) to faecal samples, an induction ratio of 4.5 was reached. Faeces seem to inhibit beta-lactamase induction in aerobic and anaerobic bacteria. The inducible enzymes produced by the anaerobic strains did not have the same properties as beta-lactamases from aerobic inducible strains, according to substrate profiles and inhibition studies. The results of the present study indicate that increased levels of beta-lactamases in the normal intestinal microflora, which often are observed after administration of beta-lactam agents, are probably due to selection of stably derepressed mutants rather than to induction of beta-lactamase production.