Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Bacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia. Fecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated. During allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold. During allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.