The Successful Recovery of Bacteriophages with Activity against Vancomycin-Resistant Enterococci (VRE) from Stool Samples of Hematopoietic Cell Transplant (HCT) Recipients

Abstract

BackgroundVancomycin-resistant Enterococci (VRE) is a well-known infectious complication among immunocompromised patients. VRE colonization of the gastro-intestinal (GI) tract could be associated with VRE bacteremia and worse outcome in hematopoietic cell transplant (HCT) recipients, in particular. Eradication of VRE colonization with systemic antibiotics is strongly discouraged for many reasons including lack of efficacy, rapid onset of resistance to the particular antibiotic used, and disruption of the normal site flora. Bacteriophages (phages) may constitute a good alternative to antibiotics to eliminate specific pathogens without disturbing the patient’s normal flora. Phages are the most abundant organisms in the biosphere. They are naturally occurring entities that play a critical role in maintaining microbial balance in every ecosystem where bacteria are present.MethodsNine HCT recipients were enrolled in this study including 5 with no VRE infection or colonization, 3 with detected VRE colonization of the GI tract, and 1 with confirmed VRE bacteremia. One-time stool samples were obtained and screened for the presence of VRE-specific phages. Individual phage plaques were then harvested, amplified, and characterized. The recovered phages were tested against VRE strains isolated from the same stool samples.ResultsFive different phages were isolated from stool samples (Figure 1A-C). All phages were able to eradicate at least one of these VRE strains (Figure 1D). The action of some of these phages complemented one another. Phages 1 and 5 as well as phages 2 and 4 could form cocktails active against all these VRE strains.ConclusionOur results highlight the feasibility and the potential success of these phages in eradicating VRE in vitro and in vivo. The isolation of phages directly from patients’ stool samples is a novel approach to obtain naturally-occurring phages already present in the gut. These VRE-specific phage cocktails may be used in future studies to eliminate VRE colonization and subsequent infections in HCT recipients.Disclosures All authors: No reported disclosures.