In vitro susceptibility of clinical Clostridioides difficile isolates to ridinilazole and ibezapolstat in Israel, 2020-2022

Background Even though they constitute a risk factor, antibiotics are still the current primary treatment of C. difficile infection. Due to C. difficile 's rapid development of resistance and high recurrences rates, there is an unmet need for new antimicrobials. In the current study, we assessed the in vitro susceptibility of clinical isolates from Israel to two recently developed antibiotics, ridinilazole and ibezpolstat, and to currently used antibiotics. Methods We collected 313 C. difficile isolates from several medical centers across Israel, that were recovered from patients of both community and hospital facilities. Isolates were typed to different strains (strain type-ST) by multi-locus sequencing typing (MLST). Susceptibility to metronidazole and vancomycin was determined by Etest; susceptibility to fidaxomicin, ridinilazole and ibezpolstat was determined by agar dilution. Results The most prevalent STs were ST42, with 39 (12.5%) isolates and ST2, with 36 isolates (11.5%). Resistance rate to metronidazole and vancomycin was low (2.2%, 1.6%, respectively). Ridinilazole (RDZ) MIC ranged between 0.06 to 0.5 mg/L, and the MIC _50/90 were 0.25/0.5 mg/L. Ibezpolstat (IBZ) had an MIC _50/90 of 4 mg/L. No significant differences were noted in MIC of different strains. Conclusions We demonstrated a potent in vitro activity of RDZ and IBZ against 313 C. difficile isolates, belonging to different STs. These two antimicrobials may serve as a treatment for C. difficile infection, as they have an excellent activity against C. difficile on one hand, and minimal effect on gut microbiome, on the other hand.