Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of <i>Clostridioides difficile</i>

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 plasmid pCD-METRO, this does not explain all cases. Objectives To identify factors that contribute plasmid-independent of C. difficile. Methods Here, we investigate in a collection clinical isolates using combination antimicrobial susceptibility testing on different solid agar media WGS selected isolates. Results We find nearly demonstrate haem-dependent increase MIC metronidazole, which some cases leads qualifying as resistant (MIC &amp;gt;2 mg/L). Moreover, an SNP haem-responsive gene hsmA, defines metronidazole-resistant lineage PCR ribotype 010/MLST ST15 also includes pCD-METRO-containing strains. Conclusions Our data haem crucial medium-dependent