In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole, vancomycin, fidaxomicin, ridinilazole and ibezapolstat,

Background: Antibiotics are currently the primary treatment of Clostridioides difficile (C. difficile) infection. Yet, due to rapid development of resistance and high recurrences rates, there is an unmet need for new antimicrobials for C. difficile infections. This study assessed the in vitro susceptibility of clinical isolates from Israel to two recently developed antibiotics, ridinilazole (RDZ) and ibezapolstat (IBZ), and to standard-of-care antibiotics. Methods: C. difficile isolates (n = 313) recovered from patients at both community and hospital medical centers across Israel, were typed to different sequence types (ST) by multi-locus sequencing typing (MLST). Susceptibility to metronidazole (MTZ) and vancomycin (VAN) was determined using the gradient strip test (Etest). Susceptibility to fidaxomicin (FDX), RDZ and IBZ was determined by agar dilution. Results: ST42 (39; 12.5%) and ST2 (36; 11.5%) were the most prevalent STs. Resistance to MTZ and VAN was low (2.2%, 1.6%, respectively), while 23 (7.35%) isolates were FDX-resistant. RDZ MIC ranged between 0.06 and 0.5 mg/L, and MIC_50/90 was 0.25/0.5 mg/L. IBZ had an MIC_50/90 of 4 mg/L. No significant differences were noted in IBZ MIC of different strains. Conclusions: RDZ and IBZ demonstrated potent in vitro activity against 313 C. difficile isolates belonging to different STs. These two antimicrobials may serve as effective agents for C. difficile infection.