Emerging metronidazole resistance in Bacteroides spp. and its association with the nim gene: a study from North India

Sethi, Sujata; Shukla, Ratnakar; Bala, Kiran; Gautam, Vikas; Angrup, Archana; Ray, Pallab

doi:10.1016/j.jgar.2018.10.015

Cited by 23 publications

(16 citation statements)

References 17 publications

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“…Phenotypic results revealed that 41% of B. fragilis were resistant to metronidazole, the commonest drug used for treating anaerobic infections [22]. This is comparable with an Indian study by Sethi et al [23] which reported 41% resistance, and [29]. Interestingly, in a study from , 14% of susceptible isolates were reported to carry the nim gene.…”

Section: Discussionsupporting

confidence: 73%

Phenotypic and genotypic correlation of antimicrobial susceptibility of Bacteroides fragilis: lessons learnt

Jha

Ragupathi

Veeraraghavan

et al. 2022

Preprint

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BackgroundBacteroides fragilis are opportunistic pathogens causing severe infections with increasing antimicrobial resistance. Since, phenotypic susceptibility testing is time-consuming and uneconomical, this necessitates a need for genotypic screening for deciding empirical therapy for B. fragilis.MethodsB. fragilis was isolated from clinical samples, exudates, tissue and body fluids collected between November 2018 and January 2020 in a tertiary care hospital. Samples were cultured in anaerobic blood agar and neomycin blood agar using the Anoxomat Mark system and species identified by MALDI-TOF-MS. Brucella agar supplemented with hemin, Vit K1 and 5% v/v laked sheep blood was used to determine the minimum inhibitory concentration by agar dilution. Genomic DNA was extracted and nim, ermF and cfiA genes were amplified, and visualized in a 2% agarose gel.ResultsOut of 51 non-duplicate B. fragilis, majority (74.5%) were recovered from exudates followed by body fluids. Isolates (n=51) expressed 45%, 41%, 16% resistance for clindamycin, metronidazole, and meropenem, respectively with least resistance to piperacillin/tazobactam (6%). Among metronidazole resistant isolates, 52% harboured nim genes in addition to 76% (23/30) of susceptible isolates. Similarly, cfiA was present in all eight meropenem resistant isolates in addition to 22% (9/41) susceptible ones. ConclusionsAll cfiA negative were phenotypically susceptible that can be employed to rule out meropenem resistance. Detecting limited genes for B. fragilis does not always correlate with phenotypic resistance, due to IS elements, efflux and other genetic determinants. Redundant use of meropenem with metronidazole should be avoided, as recommendation of metronidazole requires prior phenotypic testing due to the reported 41% resistance.

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Section: Discussionsupporting

confidence: 73%

Phenotypic and genotypic correlation of antimicrobial susceptibility of Bacteroides fragilis: lessons learnt

Jha

Ragupathi

Veeraraghavan

et al. 2022

Preprint

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“… 20 , 21 In recent reports from India, the nim gene was detected at a notably high prevalence in BFG isolated from clinical samples. 29 , 30 This study is the first surveillance on the presence of nim -carrying anaerobes among isolates from healthy individuals in Vietnam. In Vietnam, metronidazole is widely used to treat anaerobic and parasitic infections; however, metronidazole resistance or circulation of the nim gene has not yet been investigated in Vietnam.…”

Section: Discussionmentioning

confidence: 96%

Comparison of Phenotypic and Genotypic Patterns of Antimicrobial-Resistant Bacteroides fragilis Group Isolated from Healthy Individuals in Vietnam and Japan

Vu¹,

Hayashi²,

TN³

et al. 2021

IDR

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Purpose Normal non-pathogenic flora can harm the host by acting as a reservoir of resistance determinants that are potentially transferable to human pathogens. This study aimed to assess the phenotypic and genotypic antimicrobial susceptibility patterns of the Bacteroides fragilis group (BFG) isolated from healthy individuals in Vietnam and Japan in order to elucidate the prevalence of antimicrobial resistance in human flora in the two economically and geographically different countries. Materials and Methods BFG was isolated from fecal samples of 80 healthy individuals in Vietnam (n=51) and Japan (n=29). Isolated strains were identified using MALDI-TOF MS, and the minimum inhibitory concentration (MIC) of 18 antibiotics was determined using the agar dilution method. Additionally, 20 antimicrobial resistance genes were detected using standard PCR. Results A total of 139 BFG strains belonging to 11 BFG species were isolated from the two countries, with diversity in the prevalence of each species. B. fragilis was not the predominant species. Isolations from Vietnam and Japan showed some similarities in terms of MIC 50 values, MIC 90 values, and the percentage of resistant strains. However, isolations from Vietnam showed significantly higher resistance to piperacillin, cefmetazole, clindamycin, tetracycline, and minocycline. Erm B, tet 36, tet M, nim, cat A, and qnr A were not found in either country. Cep A was more common in B. fragilis than in non-fragilis Bacteroides . In contrast, cfi A, erm G, mef A, msr SA, tet X, tet X1, bex A, qnr B, and qnr S were found only in non-fragilis Bacteroides . There were differences in the prevalence of erm G, lin A, mef A, msr SA, and qnr S between isolates from Vietnam and Japan. Conclusion This study is the first report on the antimicrobial susceptibility patterns in the BFG isolated from healthy individuals in Vietnam and Japan. Compared to isolations from Japan, isolations from Vietnam showed significantly higher resistance to antimicrobial agents. The distribution of various antibiotic resistance genes also differed between the two countries.

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“…Gal et al [ 54 ] found that only about half of the 50 Bacteroides strains positive for the nim gene presented minimum inhibitory concentrations (MICs) ranging from 16 to >32 µg/mL—therefore, above the resistance breakpoint. Sethi et al [ 59 ] looked at the MTZ resistance rates in India and the relationship of isolates positive for a nim gene with resistance. They found a relatively high rate of resistance (31% compared to <1% in Europe), with a 53% rate of positivity for the nim gene.…”

Section: Metronidazolementioning

confidence: 99%

“…They found a relatively high rate of resistance (31% compared to <1% in Europe), with a 53% rate of positivity for the nim gene. Out of 20 samples, 12 that were positive for the nim gene also showed resistance to MTZ, a significant correlation [ 59 ]. Leitsch et al [ 60 ] ascertained the levels of expression of the nim genes using 2D gel electrophoresis (2DE).…”

Section: Metronidazolementioning

confidence: 99%

The Role of Nitroreductases in Resistance to Nitroimidazoles

Thomas

Gwenin

2021

Biology

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Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria. The role of nitroreductases is to activate the antimicrobial by reducing the nitro group. A decrease in the activity of nitroreductases is associated with resistance. This review will discuss the resistance mechanisms of different disease organisms, including Mycobacterium tuberculosis, Helicobacter pylori and Staphylococcus aureus, and how these impact the effectiveness of specific nitroimidazoles. Perspectives in the field of nitroimidazole drug development are also summarised.

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Emerging metronidazole resistance in Bacteroides spp. and its association with the nim gene: a study from North India

Cited by 23 publications

References 17 publications

Phenotypic and genotypic correlation of antimicrobial susceptibility of Bacteroides fragilis: lessons learnt

Phenotypic and genotypic correlation of antimicrobial susceptibility of Bacteroides fragilis: lessons learnt

Comparison of Phenotypic and Genotypic Patterns of Antimicrobial-Resistant Bacteroides fragilis Group Isolated from Healthy Individuals in Vietnam and Japan

The Role of Nitroreductases in Resistance to Nitroimidazoles

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