Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria.

BACKGROUND: Gram-negative bloodstream infections represent a significant complication facing allogeneic hematopoietic cell transplant (allo-HCT) recipients, as a result of intestinal translocation during neutropenia. In this study we sought to better understand how the composition of the intestinal microbiota is connected to risk of gram-negative bloodstream infections, expanding on our prior work in these patients.

METHODS: Fecal specimens were collected from recipients of allo-HCT and analyzed using 16SrRNA gene sequencing. Samples and clinical data extending from the pre-transplant conditioning period through stem cell engraftment were used in the analysis. Intestinal domination (relative abundance ≥30%) by gram-negative bacteria was used as predictor of gram-negative bloodstream infection using Cox proportional hazards modelling. Further analysis of microbiota composition was performed at the genus level.

RESULTS: 708 allo-HCT subjects were studied (7.5% develop gram-negative infection), with 4,768 fecal samples for analysis. Gram-negative intestinal domination was associated with subsequent bloodstream infection, which was observed overall and individually at the genus level: Escherichia, Klebsiella, Enterobacter, Pseudomonas, and Stenotrophomonas. Fluoroquinolone prophylaxis was associated with decreased bloodstream infection and intestinal colonization by gram-negative microbes. In fluoroquinolone-prophylaxed patients, Escherichia coli was more frequently observed as breakthrough, both in terms of intestinal colonization and bloodstream infections, compared with non-prophylaxed patients. Initial colonization by members of Ruminococcaceae and Bacteroidetes were associated with protection against gram-negative bloodstream infection.

CONCLUSION: Gram-negative intestinal colonization is highly predictive of bloodstream infection, in the setting of allo-HCT. Fluoroquinolones appear to reduce these infections by influencing gut colonization.