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BackgroundLowering the gut exposure to antibiotics during treatments canprevent microbiota disruption. We evaluated the effect of an activatedcharcoal-based adsorbent, DAV131A, on fecal free moxifloxacin concentration andmortality in a hamster model of moxifloxacin-induced C. difficileinfection.Methods215 hamsters receiving moxifloxacin subcutaneously (D1-D5)were orally infected at D3 with C. difficile spores. They received variousdoses (0-1800mg/kg/day) and schedules (BID, TID) of DAV131A (D1-D8).Moxifloxacin concentration and C. difficile counts were determined at D3, andmortality at D12. We compared mortality, moxifloxacin concentration and C.difficile counts according to DAV131A regimens, and modelled the link betweenDAV131A regimen, moxifloxacin concentration and mortality. ResultsAll hamstersthat received no DAV131A died, but none of those that received 1800mg/kg/day. Asignificant dose-dependent relationship between DAV131A dose and (i) mortalityrates, (ii) moxifloxacin concentration and (iii) C. difficile counts wasevidenced. Mathematical modeling suggested that (i) lowering moxifloxacinconcentration at D3, which was 58$\mu$g/g (95%CI=50-66) without DAV131A, to17$\mu$g/g (14-21) would reduce mortality by 90% and (ii) this would beachieved with a daily DAV131A dose of 703mg/kg (596-809).ConclusionsIn thismodel of C. difficile infection, DAV131A reduced mortality in a dose-dependentmanner by decreasing fecal free moxifloxacin concentration.

antimicrobial agents and chemotherapy

Protection of hamsters from mortality by reducing fecal moxifloxacin  concentration with DAV131A in a model of moxifloxacin-induced Clostridium  difficile colitis