Correlation of Clinical Severity With Stool Microbiome Changes in Clostridioides difficile Infection

Abstract

Context.— Clostridioides difficile infection (CDI) is the world-leading cause of infectious nosocomial diarrhea and pseudomembranous colitis. Antibiotics are the first line of treatment against CDI despite the high likelihood of antibiotic failure and/or recurrence. More data are needed to correlate clinical variables with 16S rRNA microbiome profiles in CDI-infected patients. Objective.— To determine the relationship(s) between a patient's clinical factors and the stool bacteriome of CDI-positive patients and CDI-negative patients with diarrheal symptoms. Design.— This study used stool samples and clinical data from 358 patients with nosocomial diarrhea, who were divided by their CDI diagnosis (CDI-negative: n = 180; CDI-positive; n = 178). The stool bacteriome was profiled by amplicon deep sequencing of the 16S rRNA gene, followed by correlating clinical data. Results.— The stool bacteriome was significantly different by severity assessment regardless of CDI status. Phyla and species varied significantly by CDI diagnosis. Severity, defined as a serum white blood cell count greater than 15 cells/μL and/or a creatinine level greater than 1.5 mg/dL, correlated significantly with dysbiosis of the stool bacteriome profile of CDI-positive patients compared to CDI-negative patients. Serum white blood cell count was significantly higher in patients with bacterial dysbiosis, and high levels of creatinine were associated with low bacteriome diversity. Conclusions.— Clinical severity of CDI influences the stool microbiome of infected patients. To date, this study has the largest data set comparing 16S rRNA microbiome profiles and clinical variables between CDI-infected and noninfected individuals.