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

Abstract : Background Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effect of an activated charcoal-based adsorbent, DAV131A, on fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced C. difficile infection. Methods 215 hamsters receiving moxifloxacin subcutaneously (D1-D5) were orally infected at D3 with C. difficile spores. They received various doses (0-1800mg/kg/day) and schedules (BID, TID) of DAV131A (D1-D8). Moxifloxacin concentration and C. difficile counts were determined at D3, and mortality at D12. We compared mortality, moxifloxacin concentration and C. difficile counts according to DAV131A regimens, and modelled the link between DAV131A regimen, moxifloxacin concentration and mortality. Results All hamsters that received no DAV131A died, but none of those that received 1800mg/kg/day. A significant dose-dependent relationship between DAV131A dose and (i) mortality rates, (ii) moxifloxacin concentration and (iii) C. difficile counts was evidenced. Mathematical modeling suggested that (i) lowering moxifloxacin concentration at D3, which was 58µg/g (95%CI=50-66) without DAV131A, to 17µg/g (14-21) would reduce mortality by 90% and (ii) this would be achieved with a daily DAV131A dose of 703mg/kg (596-809). Conclusions In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing fecal free moxifloxacin concentration.
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Submitted on : Thursday, September 21, 2017 - 9:59:47 AM
Last modification on : Wednesday, August 19, 2020 - 11:17:28 AM

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Charles Burdet, Sakina Sayah-Jeanne, Thu Thuy Nguyen, Christine Miossec, Nathalie Saint-Lu, et al.. Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with DAV131A in a model of moxifloxacin-induced Clostridium difficile colitis. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2017, ⟨10.1128/AAC.00543-17⟩. ⟨inserm-01590774⟩

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