Abstract
Abstract Background Characteristics of the gut microbiome may be useful to predict resistance to colonization and expansion of pathogenic organisms such as C. difficile. In this study, we evaluated whether inclusion of microbiome characteristics improved a clinical prediction model for in-hospital mortality. Methods Rectal or fecal swab samples were collected daily from medical intensive care unit (ICU) patients from three hospitals between 2017-2019 and underwent 16S rRNA gene sequencing of the V4 region. Patient admissions with ≥1 rectal swab collected < 48hrs from ICU admission were randomly selected 2:1 for calibration and validation analyses. Independent variables included Shannon Index, Microbiome Health Index, Community Type (CT) and relative abundance (RA) of specific bacterial taxa based on 3% sequence difference or class-level classification. The RA of each bacterial taxon was range-standardized (95%) and scaled to analyze a 10% relative difference within each taxon’s range. Logistic regression models identified microbiome characteristics at admission that were associated with in-hospital mortality. Fixed effects were included in all models to account for microbiome differences between facilities. Results There were 1365 patient admissions (910 calibration, 455 validation) analyzed (Table), of which 134 (96 calibration, 38 validation) died during hospitalization. Increase in Shannon Index by 1 [OR 0.66 (0.51-0.84), p=0.001], 10% relative increase in the RA of Bacilli [OR 1.15 (1.08-1.22), p< 0.001] and 10% relative increase in the RA of Enterococcus [OR 1.10 (1.04-1.14), p=0.001] were associated with in-hospital mortality in calibration models after controlling for Charlson Comorbidity Index [OR 1.23 (1.15-1.32), p< 0.001]. Increase in Shannon Index by 1 [OR 0.88 (0.57-1.38), p=0.581] had the same direction and similar odds in the validation cohort (Figure), supporting the findings of the calibration model. Conclusion In this secondary analysis of a large, multicenter, prospective medical ICU cohort, we found that higher alpha diversity of the gut microbiome was associated with decreased odds of in-hospital mortality. Disclosures Michael Z. David, MD PhD, Covance: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support Vincent B. Young, MD/PhD, ASM: Senior Editor|Debiopharm: Advisor/Consultant|Vedanta Biosciences: Advisor/Consultant
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