Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile.

Abstract

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.

• Authors: Ilse M Boekhoud, Igor Sidorov, Sam Nooij, Céline Harmanus, Ingrid M J G Bos-Sanders, Virginie Viprey, William Spittal, Emma Clark, Kerrie Davies, Jane Freeman, Ed J Kuijper, Wiep Klaas Smits, COMBACTE-CDI Consortium
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 76 Issue 7 Pg. 1731-1740 (06 18 2021) ISSN: 1460-2091 [Electronic] England
• PMID: 33876817 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Chemical References

• Anti-Bacterial Agents
• Metronidazole
• Heme

Topics

• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Clostridioides
• Clostridioides difficile (genetics)
• Clostridium Infections (drug therapy)
• Heme
• Humans
• Metronidazole (pharmacology)
• Microbial Sensitivity Tests
• Multilocus Sequence Typing
• Ribotyping