  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.
