Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice
| Autor: | Michelle M. Nerandzic, Curtis J. Donskey, Brigid Wilson, Myreen E. Tomas, Thriveen S.C. Mana, Miguel E. Quiñones-Mateu, Samira Joussef-Piña |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment 030106 microbiology Colonisation resistance Microbiology Vancomycin-Resistant Enterococci 03 medical and health sciences Mice Mechanisms of Resistance Medicine Animals Pharmacology (medical) Fidaxomicin Microbiome Saline Oral vancomycin Pharmacology business.industry Clostridioides difficile Microbiota Vancomycin Resistance Clostridium difficile biochemical phenomena metabolism and nutrition Anti-Bacterial Agents Infectious Diseases Clostridium Infections Vancomycin Female Anaerobic bacteria business medicine.drug |
| Popis: | Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is repopulated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline. To assess colonization resistance, subsets of mice were challenged with 10 4 CFU of C. difficile or VRE at multiple time points during and after completion of treatment. The impact of the treatments on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. Vancomycin taper-treated mice developed alterations of the microbiota and disruption of colonization resistance that was persistent 18 days after treatment. In contrast, mice treated with a 10-day course of vancomycin exhibited recovery of the microbiota and of colonization resistance by 15 days after treatment, and fidaxomicin-treated mice maintained intact colonization resistance. These findings demonstrate that alteration of the indigenous microbiota responsible for colonization resistance to C. difficile and VRE persist during and after completion of tapering courses of vancomycin. |
| Databáze: | OpenAIRE |
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