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Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients
Skye R S Fishbein1,2, Tiffany Hink3, Kimberly A Reske3
1The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
Oral vancomycin treatment for patients with positive NAAT and negative toxin tests for Clostridioides difficile infection (CDI) did not clear C. difficile. This treatment altered the gut microbiota and increased vancomycin-resistant enterococci (VRE) colonization and environmental contamination.
Area of Science:
- Microbiology
- Infectious Diseases
- Clinical Trials
Background:
- Clostridioides difficile infection (CDI) diagnosis often relies on nucleic acid amplification tests (NAAT), which have a low positive predictive value.
- Patients testing NAAT-positive but toxin enzyme immunoassay (EIA)-negative are frequently treated with oral vancomycin, despite uncertainty regarding risks and benefits.
- This population may not have active CDI but receives antibiotics, potentially leading to adverse effects and promoting antibiotic resistance.
Purpose of the Study:
- To evaluate the risk-benefit of oral vancomycin treatment in patients with NAAT-positive, EIA-negative results for CDI.
- To assess the impact of oral vancomycin on the gut microbiome, C. difficile colonization, and antibiotic-resistant organism (ARO) shedding and environmental contamination.
Main Methods:
- A double-blinded, randomized controlled trial involving 15 patients (8 vancomycin, 7 placebo) with NAAT-positive, EIA-negative stool tests.
- Collection of fecal and environmental samples before, during, and after treatment for selective culturing of C. difficile and AROs.
- Utilized shotgun metagenomics and comparative isolate genomics to analyze microbiome and resistance gene changes.
Main Results:
- Oral vancomycin did not lead to long-term clearance of C. difficile colonization (71% vs. 80% in placebo post-treatment).
- Vancomycin treatment significantly altered the gut microbiota's beta-diversity and increased macrolide-lincosamide-streptogramin (MLS) resistance genes.
- Increased colonization and environmental contamination with vancomycin-resistant enterococci (VRE) were observed in the vancomycin group (26% vs. unspecified in placebo).
Conclusions:
- Oral vancomycin treatment in this patient group does not achieve sustained C. difficile clearance.
- Vancomycin perturbs the gut microbiome and is associated with increased VRE colonization and environmental shedding.
- Further research is needed to understand the clinical outcomes and transmission dynamics of C. difficile and AROs in this population.
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