P-1830. The First-in-Class Anti-Staphylococcal Antibiotic Afabicin Desphosphono is Not Associated With Clostridioides difficile Infection in an in vitro Human Gut Model
Abstract
Abstract Background Antibiotic use is commonly associated with disruption of the healthy human gut microbiota (termed dysbiosis). Dysbiosis can diminish colonisation resistance and increase susceptibility to Clostridioides difficile infection (CDI). Use of the pathogen-specific anti-staphylococcal afabicin was not associated with dysbiosis in animals and healthy volunteers (Nowakowska et al, 2023). Here, we assessed whether this microbiota-sparing property of afabicin would limit CDI in a clinically reflective in vitro human gut model. Methods A well-established gut model was used as described previously (Baines et al, 2005). Four independent models were seeded with human fecal slurry (d0) and inoculated at d14 and d21 with C. difficile spores (107 CFU/mL). Two-week treatments were assessed beginning on d21 including (i) a CDI-positive control antibiotic levofloxacin (149.55 mg/L once daily), (ii) afabicin desphosphono high dose (35.7 mg/L twice daily [BID]), (iii) afabicin desphosphono mid dose (17.9 mg/L BID) and (iv) a vehicle control (1% DMSO BID). Endpoints for the model included facultative and obligate anaerobe counts, total viable and spore C. difficile counts and C. difficile toxin titre and were monitored daily until d63. Results Each of the afabicin desphosphono treated models displayed colonisation resistance and no evidence of C. difficile germination or toxin production for the duration of the study. Further, no relevant changes in major facultative and…
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