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

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.

Exploring host–microbiota interactions in animal models and humans

“…The temporal changes in luminal and mucosal microbial populations and their coincident impact on intestinal lymphoid populations, epithelial gene expression, and peripheral lymphoid tissues have been examined in response to antibiotics (vancomycin, metronidazole, neomycin, and ampicillin 6 amphotericin-B) provided in the drinking water or by gavage (Hill et al 2010;Reikvam et al 2011). Antibiotic perturbations of the mouse microbiota have shed insight into how vancomycin-resistant enterococcus (VRE), an organism that causes significant morbidity and mortality, can come to dominate the gut microbiome and set the stage for VRE bacteremias, which are increasingly seen in hospitalized patients (Ubeda et al 2010). Recently, mice have been used to understand the mechanisms underpinning how low-dose antibiotics promote growth in livestock, and this study raises concern for the judicious use of antibiotics in pediatric populations as juvenile obesity is becoming a global epidemic (Cho et al 2012).…”

Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis

“…43,44 Antibiotic therapy leading to VRE gastrointestinal overgrowth may lead to a unique pathogenesis and predisposition to gut translocation and bacteremia. 45,46 Specifically, perturbation of normal commensal intestinal microbiota by antibiotics and domination by VRE were shown to precede VRE BSI in allo-HCT patients. 46 Methicillin-resistant Staphylococcus aureus Methicillin-resistant Staphylococcus aureus (MRSA) produces virulent biofilms on invasive, foreign devices like endotracheal tubes and endovascular catheters.…”

“…45,46 Specifically, perturbation of normal commensal intestinal microbiota by antibiotics and domination by VRE were shown to precede VRE BSI in allo-HCT patients. 46 Methicillin-resistant Staphylococcus aureus Methicillin-resistant Staphylococcus aureus (MRSA) produces virulent biofilms on invasive, foreign devices like endotracheal tubes and endovascular catheters. 47,48 Biofilm facilitates MRSA survival and multiplication, prolonging the organism's exposure to antibiotics as well as promoting the transfer of antibiotic resistance genes among strains.…”

Cross-Resistance to Insecticides in a Malathion-Resistant Strain of Ceratitis capitata (Diptera: Tephritidae)

“…Nonetheless, it is widely known that the settlement of a prominent intestinal colonization by drug-resistant Enterococci is a decisive step in a process that can culminate in serious nosocomial infections (Arias and Murray, 2012). Once E. faecium has become the predominant species in the GI tract, it may access the bloodstream by crossing the intestinal lining, causing bacteremia and infective endocarditis (Ubeda et al, 2010). Additionally, and taking into account the long survival period of Enterococci on environmental surfaces, this stage can also serve as a reservoir for fecal contamination of the skin and urinary tract, as well as for its dissemination in the hospital setting, altogether leading to catheter-related infections (Arias and Murray, 2012).…”

“…The main reason for this phenomenon is the fact that commensal bacteria compete with Enterococci for the resources in the niche and produce substances which inhibit their growth and spread. Moreover, recent studies (Ubeda et al, 2010;Arias and Murray, 2012) have also shed light on the fact that antibiotic-depletion of the microbiota alters the immune defenses of the host (reduction of REGIII secretion), thereby indirectly facilitating colonization of the intestines by MDR Enterococci.…”