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

J Clin Invest. 2010 Dec;120(12):4332-41. doi: 10.1172/JCI43918. Epub 2010 Nov 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Bacteremia / etiology
  • Bacteremia / microbiology
  • Base Sequence
  • Cross Infection / etiology
  • Cross Infection / microbiology
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / genetics
  • Enterococcus / drug effects*
  • Enterococcus / genetics
  • Enterococcus / isolation & purification
  • Gram-Positive Bacterial Infections / etiology
  • Gram-Positive Bacterial Infections / microbiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Intestines / drug effects
  • Intestines / microbiology*
  • Metagenome / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Vancomycin Resistance

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DNA, Ribosomal