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Original Research |

Importation, Antibiotics, and Clostridium difficile Infection in Veteran Long-Term Care: A Multilevel Case–Control StudyC difficile Infection in Veteran Long-Term Care

Kevin A. Brown, PhD; Makoto Jones, MD; Nick Daneman, MD; Frederick R. Adler, PhD; Vanessa Stevens, PhD; Kevin E. Nechodom, BSc; Matthew B. Goetz, MD; Matthew H. Samore, MD; and Jeanmarie Mayer, MD
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 19 April 2016.


From University of Utah and Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs, Centers for Disease Control and Prevention, or U.S. government. Drs. Brown, Mayer, and Jones had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Grant Support: By the Centers for Disease Control and Prevention (Intra-agency agreement 11FED1106563) and the Veterans Health Administration (Centers of Innovation grant 13-414; Advanced Fellowship in Informatics [Dr. Brown]).

Disclosures: Dr. Brown reports grants from AstraZeneca outside the submitted work. Dr. Jones reports grants from the U.S. Department of Veterans Affairs and Centers for Disease Control and Prevention during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1754.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.

Reproducible Research Statement:Statistical code: Available from Dr. Brown (e-mail, kevin.brown@oahpp.ca). Study protocol and data set: Not available.

Requests for Single Reprints: Kevin A. Brown, PhD, Public Health Ontario, 480 University Avenue, Toronto, Ontario M5G1V2, Canada; e-mail, kevin.brown@oahpp.ca.

Current Author Addresses: Dr. Brown: Public Health Ontario, 480 University Avenue, Toronto, Ontario M5G1V2, Canada.

Drs. Jones, Samore, and Mayer and Mr. Nechodom: Veterans Affairs Salt Lake City Health Care System, 500 Foothill Drive, Mailstop 182, Salt Lake City, UT 84148.

Dr. Daneman: Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, G-Wing Room 106, Toronto, Ontario M4N 3M5, Canada.

Dr. Adler: Department of Mathematics, University of Utah, 155 South 1400 East, Salt Lake City, UT 84112.

Dr. Stevens: Department of Pharmacotherapy, University of Utah College of Pharmacy, 30 South 2000 East, Room 4410, Salt Lake City, UT 84112.

Dr. Goetz: Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073.

Author Contributions: Conception and design: F.R. Adler, K.A. Brown, M.M. Jones, J. Mayer, M.H. Samore, V. Stevens.

Analysis and interpretation of the data: F.R. Adler, K.A. Brown, N. Daneman, M.B. Goetz, M.M. Jones, J. Mayer, M.H. Samore, V. Stevens.

Drafting of the article: K.A. Brown, J. Mayer, V. Stevens.

Critical revision for important intellectual content: F.R. Adler, K.A. Brown, N. Daneman, M.B. Goetz, M.M. Jones, J. Mayer, M.H. Samore, V. Stevens.

Final approval of the article: F.R. Adler, K.A. Brown, N. Daneman, M.B. Goetz, M.M. Jones, J. Mayer, K. Nechodom, M.H. Samore, V. Stevens.

Statistical expertise: F.R. Adler, K.A. Brown.

Administrative, technical, or logistic support: K.A. Brown, M.H. Samore, V. Stevens.

Collection and assembly of data: K.A. Brown, M.M. Jones, J. Mayer, K. Nechodom, M.H. Samore.


Ann Intern Med. 2016;164(12):787-794. doi:10.7326/M15-1754
© 2016 American College of Physicians
Text Size: A A A

Background: Although clinical factors affecting a person's susceptibility to Clostridium difficile infection are well-understood, little is known about what drives differences in incidence across long-term care settings.

Objective: To obtain a comprehensive picture of individual and regional factors that affect C difficile incidence.

Design: Multilevel longitudinal nested case–control study.

Setting: Veterans Health Administration health care regions, from 2006 through 2012.

Participants: Long-term care residents.

Measurements: Individual-level risk factors included age, number of comorbid conditions, and antibiotic exposure. Regional risk factors included importation of cases of acute care C difficile infection per 10 000 resident-days and antibiotic use per 1000 resident-days. The outcome was defined as a positive result on a long-term care C difficile test without a positive result in the prior 8 weeks.

Results: 6012 cases (incidence, 3.7 cases per 10 000 resident-days) were identified in 86 regions. Long-term care C difficile incidence (minimum, 0.6 case per 10 000 resident-days; maximum, 31.0 cases per 10 000 resident-days), antibiotic use (minimum, 61.0 days with therapy per 1000 resident-days; maximum, 370.2 days with therapy per 1000 resident-days), and importation (minimum, 2.9 cases per 10 000 resident-days; maximum, 341.3 cases per 10 000 resident-days) varied substantially across regions. Together, antibiotic use and importation accounted for 75% of the regional variation in C difficile incidence (R2 = 0.75). Multilevel analyses showed that regional factors affected risk together with individual-level exposures (relative risk of regional antibiotic use, 1.36 per doubling [95% CI, 1.15 to 1.60]; relative risk of importation, 1.23 per doubling [CI, 1.14 to 1.33]).

Limitations: Case identification was based on laboratory criteria. Admission of residents with recent C difficile infection from non–Veterans Health Administration acute care sources was not considered.

Conclusion: Only 25% of the variation in regional C difficile incidence in long-term care remained unexplained after importation from acute care facilities and antibiotic use were accounted for, which suggests that improved infection control and antimicrobial stewardship may help reduce the incidence of C difficile in long-term care settings.

Primary Funding Source: U.S. Department of Veterans Affairs and Centers for Disease Control and Prevention.

Figures

Grahic Jump Location
Figure 1.

The association between the incidence of long-term care–onset Clostridium difficile infection and importation of cases of acute care C difficile infection (top), antibiotic use (middle), and both of these variables (bottom).

Data represent 86 Veterans Health Administration health care regions from 2006 to 2012. Point size represents the duration of follow-up, in resident-days, within each region: small points, fewer than 100 000; medium points, 100 000 to 199 999; and large points, 200 000 or more. In the bottom panel, increased importation is represented by a shift to a higher regression line.

Grahic Jump Location
Grahic Jump Location
Figure 2.

The association between antibiotic use and incidence of long-term care–onset Clostridium difficile infection among residents with and without direct antibiotic use.

Data represent 86 Veterans Health Administration regions from 2006 to 2012. Point size represents the duration of follow-up, in resident-days, within each unit: small points, fewer than 100 000; medium points, 100 000 to 199 999; large points, 200 000 or more.

Grahic Jump Location

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