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Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans
Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer
Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer
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Research Article

Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans

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Abstract

Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a growing clinical problem that increasingly defies medical intervention. Identifying patients at high risk for bacterial sepsis remains an important clinical challenge. Recent studies have shown that antibiotics can alter microbial diversity in the intestine. Here, we characterized these effects using 16s rDNA pyrosequencing and demonstrated that antibiotic treatment of mice enabled exogenously administered VRE to efficiently and nearly completely displace the normal microbiota of the small and large intestine. In the clinical setting, we found that intestinal domination by VRE preceded bloodstream infection in patients undergoing allogeneic hematopoietic stem cell transplantation. Our results demonstrate that antibiotics perturb the normal commensal microbiota and set the stage for intestinal domination by bacteria associated with hospital-acquired infections. Thus, high-throughput DNA sequencing of the intestinal microbiota could identify patients at high risk of developing bacterial sepsis.

Authors

Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer

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Figure 5

Ampicillin treatment promotes VRE intestinal colonization in mice.

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Ampicillin treatment promotes VRE intestinal colonization in mice.
(A) T...
(A) The number of VRE CFUs in the small intestine or cecum of untreated mice, mice treated for 1 week with ampicillin before infection and kept on ampicillin after VRE infection, or mice switched back to antibiotic-free water 1 day after infection and allowed to recover. Mice were infected with 108 CFUs. Samples were harvested on different days after VRE infection. n ≥ 6 mice per group and day, except day 15 ampicillin (n = 3). (B) Phylogenetic classification of 16S rDNA frequencies or (C) number of 16s rDNA copies in the ileum and cecum of untreated mice as well as ampicillin-treated mice, infected or not with VRE after 1 week of treatment, and either treated for 8 days or allowed to recover starting at 1 day after infection. The most predominant bacterial populations identified are color coded as indicated. Each bar represents the microbiota composition of an individual mouse.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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