Mechanisms of Bacteroides fragilis resistance to metronidazole

Metronidazole-resistant Bacteroides fragilis (B. fragilis) have been reported worldwide. Several mechanisms contribute to B. fragilis resistance to metronidazole. In some cases, the mechanisms of metronidazole resistance are unknown. Understanding the mechanisms of resistance is important for therapy, the design of new alternative drugs, and control of resistant strains. In this study, a comprehensive review of the B. fragilis resistance mechanisms to metronidazole was prepared. The rate of metronidazole-resistant B. fragilis has been reported as ranging from 0.5% to 7.8% in many surveys. According to CLSI, isolates with MICs ≥32 μg/mL are considered to be metronidazole-resistant. In the majority of cases, metronidazole resistance in B. fragilis is coupled with the existence of nim genes. Metronidazole resistance could be induced in nim-negative strains by exposure to sub-MIC levels of metronidazole. There are multi-drug efflux pumps in B. fragilis which can pump out a variety of substrates such as metronidazole. The recA overexpression and deficiency of feoAB are other reported metronidazole resistance mechanisms in this bacterium.