Da Volterra, a biotechnology company located in Paris, France, is developing breakthrough therapies to combat antibiotic resistance and prevent Clostridium difficile infections (CDI) via protection of the intestinal microbiota during antibiotic treatments. A recent publication by Da Volterra in Antimicrobial Agents and Chemotherapy shows that DAV131, an absorbent based therapeutic, prevents CDI related death in hamsters when given in combination with moxifloxacin. DAV131 is the rodent-adapted form of DAV132 that is designed to prevent C. difficile infections for at risk human patients.
This new publication demonstrates that the innovative strategy, on which DAV132 is based, is able in hamsters to prevent CDI infections triggered by treatments with antibiotics such as moxifloxacin.
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.
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.
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).
In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing fecal free moxifloxacin concentration.
Burdet, C., Sayah-Jeanne, S., Nguyen, TT., Miossec, C., Saint-Lu, N., Weiss, W., Andremont, A., Mentré, F., de Gunzburg, J. (2017), 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. doi: 0.1128/AAC.00543-17
Copyright © 2017 American Society for Microbiology.
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