Cargando…

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

Descripción completa

Detalles Bibliográficos
Autores principales: Boekhoud, Ilse M, Sidorov, Igor, Nooij, Sam, Harmanus, Céline, Bos-Sanders, Ingrid M J G, Viprey, Virginie, Spittal, William, Clark, Emma, Davies, Kerrie, Freeman, Jane, Kuijper, Ed J, Smits, Wiep Klaas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212768/
https://www.ncbi.nlm.nih.gov/pubmed/33876817
http://dx.doi.org/10.1093/jac/dkab097
Descripción
Sumario: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.