Enteric Microbiome Features that Contribute to Gram-Negative Bloodstream Infections in Hematopoietic Cell Transplant...

Hematopoietic cell transplant (HCT) recipients colonized with fluoroquinolone-resistant Enterobacterales (FQRE) frequently develop bloodstream infection (BSI) from their colonizing FQRE strains while receiving fluoroquinolone prophylaxis during neutropenia. However, enteric microbiome features that contribute to this increased BSI risk are unknown.

16S ribosomal RNA gene sequencing and quantitative cultures were performed on stool samples collected before and after the initiation of levofloxacin prophylaxis during a single-center prospective study of patients undergoing HCT. Enteric microbiome features were compared between FQRE-colonized and non-colonized patients and between FQRE-colonized patients who did and did not develop FQRE BSI.

We evaluated samples from 26 participants colonized with FQRE pre-HCT (nine developed FQRE BSI) and 69 not colonized with FQRE (none developed FQRE BSI). FQRE-colonized participants had a higher median baseline relative abundance of Enterobacterales (4.7% vs.0.3%) and Bacteroidales (14.3% vs. 0.5%) than non-colonized participants. After starting levofloxacin prophylaxis, the relative abundance of Enterobacterales declined in all but one HCT recipient without FQRE colonization, but increased in approximately one-third of participants with FQRE, including those who subsequently developed FQRE BSI. Among FQRE-colonized HCT recipients, there were no significant differences in FQRE colonization density or microbial diversity or composition between those who did and did not develop FQRE BSI.

FQRE-colonized HCT recipients have a distinct microbiome composition compared to HCT recipients without FQRE colonization and frequently have an expansion of Enterobacterales during levofloxacin prophylaxis that precedes FQRE BSI. Additional studies of FQRE-colonized HCT recipients are needed to clarify microbiome risk factors for FQRE BSI.