Risk factors of fecal toxigenic or non-toxigenic Clostridium difficile colonization: impact of Toll-like receptor polymorphisms and prior antibiotic exposure

PLoS One. 2013 Jul 25;8(7):e69577. doi: 10.1371/journal.pone.0069577. Print 2013.

Abstract

Background: This study is to investigate the significance and risk factors of fecal toxigenic (tCdC) or non-toxigenic Clostridium difficile colonization (ntCdC) among hospitalized patients.

Methods: Adults admitted to medical wards in a district hospital between January 2011 and June 2012 were enrolled, and those with a history of colectomy, C. difficile fecal colonization or infection or receipt of either metronidazole or oral vancomycin within 3 months, were excluded. Stools collected within 48 hours after admission and every week during hospitalization were cultured for C. difficile.

Findings: Among the 441 enrolled patients, 84 (20.0%) had CdC at initial screening, including 58 (13.2%) with tCdC and 26 (6.8%) with ntCdC. Among patients with initial negative fecal screening for CdC, it took an average of 70.6 days or 66.5 days to develop tCdC or ntCdC during the study period. Finally 78 (17.7%) had tCdC and 34 (7.7%) had ntCdC. During the follow-up period, the patients with tCdC had a higher risk of CDAD (11/79, 14.1%) than those without CdC (3/328, 0.9%) and those with ntCdC (0/34, 0%) (P<0.001). In multivariate analysis, the TLR4 rs1927914 polymorphism (GG genotype) (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.6-11.8, P = 0.003) and recent cefepime therapy (OR 5.3, 95% CI 2.1-13.2, P<0.001) were independently associated with tCdC, whereas recent cefuroxime (OR 11.7, 95% CI 2.3-60.2, P = 0.003) and glycopeptide therapy (OR 10.9, CI: 2.1-57.2, P = 0.005) associated with ntCdC.

Conclusion: The incidence of CDAD is highest in patients with tCdC and lowest in patients with ntCdC, and the TLR4 rs1927914 polymorphism GG genotype and recent cefepime therapy were independently associated with tCdC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Infective Agents / pharmacology*
  • Cefepime
  • Cefuroxime / pharmacology
  • Cephalosporins / pharmacology
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / immunology
  • Clostridioides difficile / pathogenicity
  • Enterocolitis, Pseudomembranous / drug therapy
  • Enterocolitis, Pseudomembranous / genetics*
  • Enterocolitis, Pseudomembranous / immunology
  • Enterocolitis, Pseudomembranous / microbiology
  • Feces / microbiology
  • Female
  • Humans
  • Male
  • Metronidazole / pharmacology
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Risk Factors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*
  • Vancomycin / pharmacology

Substances

  • Anti-Infective Agents
  • Cephalosporins
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Metronidazole
  • Vancomycin
  • Cefepime
  • Cefuroxime

Grants and funding

The study is supported by the grants from the National Science Council (100-2314-B-675-002) and Department of Health, Executive Yuan (DOH100-TD-B-111-002), Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.