Gut Colonization With Vancomycin-Resistant Enterococcus Shapes the Gut Microbiome in the Intensive Care Unit

Introduction: Gut pathogen colonization with Vancomycin-resistant Enterococcus (VRE) is common in the intensive care unit (ICU) and is associated with worse clinical outcomes, yet the timing of VRE colonization and its collateral effects on the gut microbiome are incompletely understood. Methods: Medical ICU patients admitted with sepsis and receiving broad-spectrum antibiotics were sampled via deep rectal swabs at ICU admission and on ICU Day 3, 7, 14, and 30. Rectal swabs were cultured for VRE on selective media and analyzed via 16S rRNA gene sequencing. Results: Ninety patients were sampled (340 longitudinal swabs). VRE positivity rose from 20% at ICU admission to a peak of 33% by ICU Day 14 and then modestly declined to 31% by ICU Day 30. Paralleling this, alpha diversity fell while Enterococcus relative abundance rose through ICU Day 14 with both returning to baseline by ICU Day 30. The median relative abundance of Enterococcus was 38% (IQR 7.4 to 75%) for VRE positive samples compared to 0.01% (IQR 0 to 19%) for VRE negative samples (rank-sum p<0.01); 38 samples had >= 90% Enterococcus and 8 samples were 100% Enterococcus by sequencing. VRE was associated with lower alpha diversity (median Shannon index of 1.90 (IQR 0.89 to 2.66) if VRE positive versus 2.64 (IQR 1.58 to 3.22) if VRE negative, p<0.01). Conclusion: VRE gut colonization peaked at ICU Day 14 followed by a modest decline and was associated with low alpha diversity. Improved understanding of dynamic changes in the gut microbiome may facilitate successful future ICU interventions.