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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

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.