In vivoefficacy of fidaxomicin againstrpoBmutantClostridioides difficileinfection
Abstract
Objectives
Clostridioides difficileinfection (CDI) is a well-known healthcare-associated diarrheal disease. Fidaxomicin, a key antibiotic used to treat CDI, targetsrpoB. However, some clinical isolates have mutations inrpoB, which reduces their susceptibility to this antibiotic. In this study, the effects ofrpoBmutations on the virulence ofC. difficileand efficacy of fidaxomicin against CDI were evaluatedin vivo.
Methods
AnrpoBmutant strain (C. difficileG1073R-2024) with reduced fidaxomicin susceptibility was generated through spontaneous induction in a murine CDI model from the parental strainC. difficileVPI 10463. The virulence and therapeutic responses of the mutant strain were compared with those of the parental strain using a CDI model, including survival rate, body weight changes, clinical scores, and bacterial loads in feces.
Results
C. difficileG1073R-2024 had an amino acid alteration in Gln1073Arg and the minimum inhibitory concentration of fidaxomicin was >64 μg/mL.In vivovirulence was not significantly different between strains. Fidaxomicin treatment resulted in 100% survival rates and a comparable reduction in the bacterial load for both strains.
Conclusions
Fidaxomicin was effective against CDI caused by therpoBmutant strain. The emergence of such mutations highlights the need for ongoing surveillance of drug resistance trends in clinical settings.
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