Clinical failure of an extended-pulsed fidaxomicin regimen associated with emergence of a Clostridioides difficile isolate with reduced fidaxomicin susceptibility in an elderly man.

The clinical significance of Clostridioides difficile isolates with reduced fidaxomicin susceptibility is uncertain. We report treatment failure of extended-pulsed fidaxomicin treatment during every other day pulsing associated with emergence of a C. difficile isolate with reduced fidaxomicin susceptibility and a novel rpoC gene mutation, resulting in a novel amino acid substitution (R89K). The reduced susceptibility isolate had no reduction in growth or ability to colonize mice, but in vitro sporulation and toxin production were reduced.