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

Yuan-Pin Hung,Yi-Hui Wu,Lei Wan,Jen-Chieh Lee,Tai-Chieh Wu,Pei-Jane Tsai,Hsiao-Ju Lin,Chih-I Lee,Wen-Chien Ko,Hsiu-Chuan Liu,Markus M Heimesaat

doi:10.1371/journal.pone.0069577

Yuan-Pin Hung, Yi-Hui Wu + Show 9 more

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https://doi.org/10.1371/journal.pone.0069577

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Abstract

BackgroundThis study is to investigate the significance and risk factors of fecal toxigenic (tCdC) or non-toxigenic Clostridium difficile colonization (ntCdC) among hospitalized patients.MethodsAdults 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.FindingsAmong 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.ConclusionThe 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.

Highlights

Clostridium difficile is a major cause of nosocomial antibioticassociated diarrhea due to the production of toxins A and B
The incidence of C. difficile-associated diarrhea (CDAD) is highest in patients with Toxigenic C. difficile colonization (tCdC) and lowest in patients with non-toxigenic Clostridium difficile colonization (ntCdC), and the TLR4 rs1927914 polymorphism GG genotype and recent cefepime therapy were independently associated with tCdC
C. difficile is frequently transmitted in healthcare settings via the hands of healthcare workers, and C. difficile-associated diarrhea (CDAD) is an important infection control issue

Summary

Introduction

Clostridium difficile is a major cause of nosocomial antibioticassociated diarrhea due to the production of toxins A and B. C. difficile infection was 42.6 cases per 100,000 patient-days and was increasing in recent years in Taiwan in our previous retrospective study [1]. The use of antibiotics, prolonged hospitalization, the presence of comorbidity with functional impairment or immune gene polymorphism (such as IL-8) are associated with increased rates of C. difficile infection and disease recurrence [2,3,4]. The interaction of C. difficile with the innate immune system likely plays a major role in the pathogenesis of colitis or pseudomembranous disease, yet it remains an area that has received little attention. This study is to investigate the significance and risk factors of fecal toxigenic (tCdC) or non-toxigenic Clostridium difficile colonization (ntCdC) among hospitalized patients

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