< em > In vitro < /em > and < em > in vivo < /em > activities, absorption, tissue distribution and excretion studies of OBP-4, a potential anti- < em > Clostridioides difficile < /em > agent

Antimicrob Agents Chemother. 2021 Apr 5:AAC.00581-21. doi: 10.1128/AAC.00581-21. Online ahead of print.ABSTRACTClostridioides* difficile infection (CDI) is considered to be a major concern of the healthcare system globally with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile, and its absorption, distribution and excretion (ADE) profiles in rats. In vitro assays indicated OBP-4 was active against all tested C. difficile strains with MICs ranged from 0.25 to 1 mg/L. Meanwhile, OBP-4 showed a complete inhibition on spore formation at the concentration of 0.5× MIC. In the mouse model of CDI, 5-day oral treatment of OBP-4 provided a complete protection from death and CDI recurrence for infected mice. However, cadazolid (CZD) and vancomycin (VAN) showed less protection for infected mice than did OBP-4 in terms of diarrhea and weight loss, especially VAN. Subsequently, ADE investigations of OBP-4 with a reliable LC-MS/MS method showed a extremely low systemic exposure and predominant fecal excretion, thus resulting in a high local concentration of OBP-4 in the intestinal tract - the site of CDI. These results demonstrated that OBP-4 possess good activity against C. difficile and favorable ADE characteristics for oral treatment of CDI, which ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Source Type: research