期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 76, 期 7, 页码 1731-1740出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkab097
关键词
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资金
- Innovative Medicines Initiative 2 Joint Undertaking [777362]
- Netherlands Organisation for Scientific Research [864.13.003]
- Leiden University Medical Center
The study found that nearly all isolates of C. difficile from infected patients displayed a haem-dependent increase in metronidazole resistance. Additionally, a key SNP in the haem-responsive gene was identified. These results demonstrate the crucial role of haem in mediating resistance to metronidazole in C. difficile.
Background: Until recently, metronidazole was the first-Line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases. Objectives: To identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile. Methods: Here, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile using a combination of antimicrobial susceptibility testing on different solid agar media and WGS of selected isolates. Results: We find that nearly all isolates demonstrate a haem-dependent increase in the MIC of metronidazole, which in some cases Leads to isolates qualifying as resistant (MIC >2 mg/L). Moreover, we find an SNP in the haem-responsive gene hsmA, which defines a metronidazole-resistant Lineage of PCR ribotype 010/MLST ST15 isolates that also includes pCD-METRO-containing strains. Conclusions: Our data demonstrate that haem is crucial for medium-dependent metronidazole resistance in C. difficile.
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