Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection

• Published in: Antimicrobial agents and chemotherapy 2018-10, Vol.62 (10)
• Main Authors: Burdet, Charles, Sayah-Jeanne, Sakina, Nguyen, Thu Thuy, Hugon, Perrine, Sablier-Gallis, Frédérique, Saint-Lu, Nathalie, Corbel, Tanguy, Ferreira, Stéphanie, Pulse, Mark, Weiss, William, Andremont, Antoine, Mentré, France, de Gunzburg, Jean
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents; Clostridium Infections; Dysbiosis; Life Sciences; Mechanisms of Action: Physiological Effects; Quantitative Methods
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00925-18

Antibiotic disruption of the intestinal microbiota favors colonization by Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis and quantified the link between this intensity and mortality. We administered either moxifloxacin ( = 70) or clindamycin ( = 60) to hamsters by subcutaneous injection from day 1 (D ) to D and challenged them with a toxigenic strain at D Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D and D using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of challenge and studied their capacity to predict subsequent death of the animals. Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis, and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis ( < 10 for the change of Shannon index in moxifloxacin-treated animals and < 10 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the receiver operating curve (ROC) of 0.89 (95% confidence interval [CI], 0.82, 0.95) and 0.95 (0.90, 0.98), respectively. Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency on the DAV131A dose; mortality after challenge was related to the intensity of dysbiosis in similar manners with the two antibiotics.