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

TL;DR

This study demonstrates that DAV131A, an activated charcoal-based adsorbent, reduces fecal moxifloxacin levels and significantly decreases mortality in hamsters with moxifloxacin-induced C. difficile colitis, suggesting a potential protective strategy.

Contribution

First to show dose-dependent reduction of fecal antibiotic concentration and mortality using DAV131A in a hamster model of C. difficile infection.

Findings

Higher DAV131A doses lower fecal moxifloxacin levels.

Reduced moxifloxacin levels correlate with decreased mortality.

Mathematical modeling predicts optimal dosing to prevent death.

Abstract

BackgroundLowering 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.Methods215 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. ResultsAll 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 58$\mu$g/g (95%CI=50-66) without DAV131A, to 17$\mu$g/g (14-21) would reduce mortality by 90% and (ii) this would be achieved with a daily DAV131A dose of 703mg/kg (596-809).ConclusionsIn this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing fecal free moxifloxacin concentration.