Molecular study on metronidazole resistance in Bacteroides fragilis group isolates from a South Indian tertiary care center

Bacteroides species are found in abundance in the human gut microbiome. When they are transferred out of their gut niche, they can cause infections with high mortality and morbidity. These infections are largely neglected in clinical settings because of their polymicrobial nature and the challenge of isolating them in routine laboratories [1]. Metronidazole, one of the commonly used drugs for prophylaxis and treatment of anaerobic infections, is showing signs of resistance, which is commonly linked to nitroimidazole resistance genes (nim). Additionally, Bacteroides species tend to show decreased susceptibility to other clinically important antibiotics, such as β-lactams, clindamycin, tetracyclines, carbapenem, etc., which limits the range of therapeutic choices.

The first Bacteroides fragilis strain (NCTC 11295) to develop metronidazole resistance was isolated from a Crohn's disease patient in Newcastle (United Kingdom) in 1978 [2]. Other resistant strains have since been discovered in clinical specimens [[3], [4], [5], [6], [7], [8], [9], [10], [11]]. Despite metronidazole's widespread use, research on resistance mechanisms has been sparse. The nim genes, which have 12 isoforms (nimA-L) and can be expressed on plasmids or chromosomes, are crucial for conferring resistance to metronidazole among BFG [12]. Despite the fact that nim-related metronidazole resistance is uncommon globally, such isolates have been reported from Europe, Africa and the Middle East [3,4,13]. According to different reports from Canada, the United States, Asia, Europe, the Middle East, and Africa, Bacteroides spp. exhibit metronidazole resistance at a rate of 0.5–7.8% [14]. Although their understanding is still lacking, a variety of potential resistance mechanisms, such as the overexpression of RecA protein, FeoAB deficiency, and multidrug efflux pumps, have been postulated [15]. Furthermore, nim negative Bacteroides strains can develop metronidazole resistance by being exposed to sub-inhibitory concentrations of the drug [10,14].

The purpose of this study was to analyse the distribution of nim genes and associated metronidazole susceptibility among the Bacteroides isolates at our hospital owing to the increasing metronidazole resistance as evidenced from the few Indian studies. The correlation between nim gene-carrying strains and metronidazole susceptibility were also investigated. Understanding the metronidazole resistance status and the probable mechanism of resistance in these isolates would help in early initiation of appropriate antimicrobial therapy and further prevention of resistant strains propagating in the community.

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