In vitro selection of ertapenem and piperacillin/tazobactam-resistant strains of Bacteroides fragilis and analysis of their virulence in gnotobiotic mice.

Ertapenem and piperacillin/tazobactam are beta-lactam antibiotics with a broad spectrum of activity, used for the treatment of mixed infections, in which Bacteroides fragilis plays an important etiological role. The aim of this study was to select strains of B. fragilis resistant to these drugs and correlate the phenotype profiles of these lineages with changes in the virulence of the original bacterium. B. fragilis ATCC 25285, sensitive to the drugs listed, was used in this study. Strains resistant to these drugs were obtained by multi-step method and this condition was confirmed by comparing the time-kill curve of the original strain with those curves obtained from derived-resistant strains. To assess the virulence, germ-free mice were challenged intragastrically with the original strain or those derived-resistant. The mouse infection by the piperacillin/tazobactam-resistant B. fragilis strain produced increased levels of C-reactive protein, alkaline phosphatase and white blood cells and reduced platelet counts, what may indicate that acquisition of piperacillin/tazobactam resistance may enhance the pathogenic properties of these B. fragilis strains.