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

Arch Pathol Lab Med. 2023 Jul 1;147(7):774-785. doi: 10.5858/arpa.2021-0636-OA.

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.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Clostridioides difficile* / genetics
  • Clostridium Infections* / diagnosis
  • Clostridium Infections* / drug therapy
  • Clostridium Infections* / microbiology
  • Creatinine
  • Cross Infection* / drug therapy
  • Diarrhea / drug therapy
  • Diarrhea / microbiology
  • Dysbiosis / drug therapy
  • Humans
  • Microbiota*
  • RNA, Ribosomal, 16S / genetics

Substances

  • RNA, Ribosomal, 16S
  • Creatinine
  • Anti-Bacterial Agents