Risk Factors for Community-Associated  Clostridium difficile  Infection in Adults: A Case-Control Study

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Abstract

Background

An increasing proportion of Clostridium difficile infections (CDI) in the United States are community-associated (CA). We conducted a case-control study to identify CA-CDI risk factors.

Methods

We enrolled participants from 10 US sites during October 2014–March 2015. Case patients were defined as persons age ≥18 years with a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization who had no admission to a health care facility in the prior 12 weeks and no prior CDI diagnosis. Each case patient was matched to one control (persons without CDI). Participants were interviewed about relevant exposures; multivariate conditional logistic regression was performed.

Results

Of 226 pairs, 70.4% were female and 52.2% were ≥60 years old. More case patients than controls had prior outpatient health care (82.1% vs 57.9%; P < .0001) and antibiotic (62.2% vs 10.3%; P < .0001) exposures. In multivariate analysis, antibiotic exposure—that is, cephalosporin (adjusted matched odds ratio [AmOR], 19.02; 95% CI, 1.13–321.39), clindamycin (AmOR, 35.31; 95% CI, 4.01–311.14), fluoroquinolone (AmOR, 30.71; 95% CI, 2.77–340.05) and beta-lactam and/or beta-lactamase inhibitor combination (AmOR, 9.87; 95% CI, 2.76–340.05),—emergency department visit (AmOR, 17.37; 95% CI, 1.99–151.22), white race (AmOR 7.67; 95% CI, 2.34–25.20), cardiac disease (AmOR, 4.87; 95% CI, 1.20–19.80), chronic kidney disease (AmOR, 12.12; 95% CI, 1.24–118.89), and inflammatory bowel disease (AmOR, 5.13; 95% CI, 1.27–20.79) were associated with CA-CDI.

Conclusions

Antibiotics remain an important risk factor for CA-CDI, underscoring the importance of appropriate outpatient prescribing. Emergency departments might be an environmental source of CDI; further investigation of their contribution to CDI transmission is needed.

Related collections

Most cited references 28

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Diverse sources of C. difficile infection identified on whole-genome sequencing.

David W. Eyre, Madeleine L. Cule, Daniel J Wilson … (2013)

It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions. From September 2007 through March 2011, we performed whole-genome sequencing on isolates obtained from all symptomatic patients with C. difficile infection identified in health care settings or in the community in Oxfordshire, United Kingdom. We compared single-nucleotide variants (SNVs) between the isolates, using C. difficile evolution rates estimated on the basis of the first and last samples obtained from each of 145 patients, with 0 to 2 SNVs expected between transmitted isolates obtained less than 124 days apart, on the basis of a 95% prediction interval. We then identified plausible epidemiologic links among genetically related cases from data on hospital admissions and community location. Of 1250 C. difficile cases that were evaluated, 1223 (98%) were successfully sequenced. In a comparison of 957 samples obtained from April 2008 through March 2011 with those obtained from September 2007 onward, a total of 333 isolates (35%) had no more than 2 SNVs from at least 1 earlier case, and 428 isolates (45%) had more than 10 SNVs from all previous cases. Reductions in incidence over time were similar in the two groups, a finding that suggests an effect of interventions targeting the transition from exposure to disease. Of the 333 patients with no more than 2 SNVs (consistent with transmission), 126 patients (38%) had close hospital contact with another patient, and 120 patients (36%) had no hospital or community contact with another patient. Distinct subtypes of infection continued to be identified throughout the study, which suggests a considerable reservoir of C. difficile. Over a 3-year period, 45% of C. difficile cases in Oxfordshire were genetically distinct from all previous cases. Genetically diverse sources, in addition to symptomatic patients, play a major part in C. difficile transmission. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.).

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Incidence of Clostridium difficile infection in inflammatory bowel disease.

K Reske, Joseph Rodemann, D Seo … (2007)

Clostridium difficile-associated disease (CDAD) rates have been increasing. We sought to determine whether CDAD incidence has increased specifically in hospitalized patients with IBD. We also explored possible differences in the risk for and time to presentation of CDAD between IBD and non-IBD patients. We analyzed hospital admissions from 1998-2004 for demographics, length of stay, C difficile infections, and time from admission to a positive C difficile test. We calculated CDAD incidence for non-IBD, all IBD, CD, and UC admissions and used logistic regression to estimate the risk for CDAD. CDAD incidence increased in each group and was higher in all IBD than non-IBD groups. During the observation period, CDAD rates approximately doubled in CD (9.5 to 22.3/1000 admissions) and tripled in UC (18.4 to 57.6/1000). Length of stay was similar among the groups. For all years combined, the adjusted odds ratios for CDAD in all IBD, CD, and UC admissions were 2.9 (95% confidence interval, 2.1-4.1), 2.1 (1.3-3.4), and 4.0 (2.4-6.6), respectively. The median times from admission to a positive C difficile test result for non-IBD, CD, and UC were 4.0, 0.8, and 0.5 days, respectively. CDAD incidence in IBD has increased and is higher than in the non-IBD population. IBD and UC patients in particular have a higher risk for CDAD. C difficile infections in IBD are confirmed predominantly within 48 hours of admission, suggesting most were acquired before hospitalization.

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Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011.

Amit Chitnis, Stacy Holzbauer, Ruth M Belflower … (2013)

Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. Active population-based and laboratory-based CDI surveillance in 8 US states. Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

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Author and article information

Journal

Journal ID (nlm-ta): Open Forum Infect Dis

Journal ID (iso-abbrev): Open Forum Infect Dis

Journal ID (publisher-id): ofid

Title: Open Forum Infectious Diseases

Publisher: Oxford University Press (US )

ISSN (Electronic): 2328-8957

Publication date Collection: Fall 2017

Publication date (Electronic): 26 October 2017

Volume: 4

Issue: 4

Electronic Location Identifier: ofx171

Affiliations

[1 ] Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia;

[2 ] Emory University Department of Medicine , Atlanta, Georgia;

[3 ] Georgia Emerging Infections Program , Decatur, Georgia;

[4 ] Atlanta Veterans Affairs Medical Center , Atlanta, Georgia;

[5 ] Atlanta Research and Education Foundation , Decatur, Georgia;

[6 ] Minnesota Department of Health , St Paul, Minnesota;

[7 ] Career Epidemiology Field Officer Program, Centers for Disease Control and Prevention , Atlanta, Georgia;

[8 ] University of New Mexico, New Mexico Emerging Infections Program , Albuquerque, New Mexico;

[9 ] New York Emerging Infections Program and University of Rochester Medical Center , Rochester, New York;

[10 ] Tennessee Department of Health , Nashville, Tennessee;

[11 ] Yale School of Public Health, Connecticut Emerging Infections Program , New Haven, Connecticut;

[12 ] Maryland Department of Health and Mental Hygiene , Baltimore, Maryland;

[13 ] University of California, San Francisco, School of Medicine , San Francisco, California;

[14 ] California Emerging Infections Program , Oakland, California;

[15 ] Colorado Department of Public Health and Environment , Denver, Colorado;

[16 ] Oregon Health Authority , Portland, Oregon;

[17 ] Loyola University Chicago Stritch School of Medicine , Maywood, Illinois;

[18 ] Edward Hines, Jr. Veterans Affairs Hospital , Hines, Illinois

Author notes

Correspondence: A. Y. Guh, MD, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS A-31, Atlanta, GA 30329 ( ggt4@ 123456cdc.gov ).

Article

Publisher ID: ofx171

DOI: 10.1093/ofid/ofx171

PMC ID: 5903408

PubMed ID: 29732377

SO-VID: 7e474263-de9a-488e-a077-6884336649de

License:

This work is written by (a) US Government employee(s) and is in the public domain in the US.

History

Date received : 04 June 2017

Date accepted : 08 August 2017

Page count

Pages: 8

Funding

Funded by: National Center for Emerging and Zoonotic Infectious Diseases 10.13039/100006088

Risk Factors for Community-Associated Clostridium difficile Infection in Adults: A Case-Control Study

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Abstract

Background

Methods

Results

Conclusions

Related collections

Decoding Infection and Transmission

Most cited references 28

Diverse sources of C. difficile infection identified on whole-genome sequencing.

Incidence of Clostridium difficile infection in inflammatory bowel disease.

Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011.

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