Epidemiological and genomic characterization of community-acquired Clostridium difficile infections

Christina S Thornton,Gisele Peirano,Joseph E Rubin,Dylan R Pillai,Alexander L Greninger,Charles Y Chiu

doi:10.1186/s12879-018-3337-9

Abstract

BackgroundClostridium difficile infection (CDI) is a major cause of morbidity and mortality in North America and Europe. The aim of this study was to identify epidemiologically-confirmed cases of community-acquired (CA)-CDI in a large North American urban center and analyze isolates using multiple genetic and phenotypic methods.MethodsSeventy-eight patients testing positive for C. difficile from outpatient clinics were further investigated by telephone questionnaire. CA-CDI isolates were characterized by antibiotic susceptibility, pulsed-field gel electrophoresis and whole genome sequencing. CA-CDI was defined as testing positive greater than 12 weeks following discharge or no previous hospital admission in conjunction with positive toxin stool testing.Results51.3% (40/78) of the patients in this study were found to have bona fide CA-CDI. The majority of patients were female (71.8% vs. 28.2%) with 50–59 years of age being most common (21.8%). Common co-morbidities included ulcerative colitis (1/40; 2.5%), Crohn’s disease (3/40; 7.5%), celiac disease (2/40; 5.0%) and irritable bowel syndrome (8/40; 20.0%). However, of 40 patients with CA-CDI, 9 (29.0%) had been hospitalized between 3 and 6 months prior and 31 (77.5%) between 6 and 12 months prior. The hypervirulent North American Pulostype (NAP) 1-like (9/40; 22.5%) strain was the most commonly identified pulsotype. Whole genome sequencing of CA-CDI isolates confirmed that NAP 1-like pulsotypes are commonplace in CA-CDI. From a therapeutic perspective, there was universal susceptibility to metronidazole and vancomycin.ConclusionsAll CA-CDI cases had some history of hospitalization if the definition were modified to health care facility exposure in the last 12 months and is supported by the genomic analysis. This raises the possibility that even CA-CDI may have nosocomial origins.

Highlights

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in North America and Europe
The incidence, mortality and associated health care costs associated with CDI are significant, with 10–25% of all cases of antibiotic-associated diarrheal onset attributed to CDI [4]
community-acquired CDI (CA-CDI) rates are on the rise, with 20–45% [1, 9] of all CDI cases attributed to community onset, and a further 22% of patients having no history of antimicrobial several months prior to CDI onset [12]

Summary

Introduction

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in North America and Europe. Clostridium difficile infections (CDI) are the most common cause of infectious diarrheal infection amongst hospitalized patients in North America and Europe [1]. The incidence, mortality and associated health care costs associated with CDI are significant, with 10–25% of all cases of antibiotic-associated diarrheal onset attributed to CDI [4]. The definition of CA-CDI requires the patient to not have been in a hospital or health care facility within the previous 12 weeks or to develop CDI symptoms within 48 h of hospital admission [11]. Nosocomial CDI requires that symptoms occur greater than 48 h after hospital admission or in less than 4 weeks after discharge from a health care facility [11]. CA-CDI rates are on the rise, with 20–45% [1, 9] of all CDI cases attributed to community onset, and a further 22% of patients having no history of antimicrobial several months prior to CDI onset [12]

Objectives

Methods

Results