• Kevin Brown, Kim Valenta, David Fisman, Andrew Simor, and Nick Daneman.
• Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
• JAMA Intern Med. 2015 Apr 1;175(4):626-33.

ImportanceOnly a portion of hospital-acquired Clostridium difficile infections can be traced back to source patients identified as having symptomatic disease. Antibiotic exposure is the main risk factor for C difficile infection for individual patients and is also associated with increased asymptomatic shedding. Contact with patients taking antibiotics within the same hospital ward may be a transmission risk factor for C difficile infection, but this hypothesis has never been tested.ObjectivesTo obtain a complete portrait of inpatient risk that incorporates innate patient risk factors and transmission risk factors measured at the hospital ward level and to investigate ward-level rates of antibiotic use and C difficile infection risk.Design, Setting, And PatientsA 46-month (June 1, 2010, through March 31, 2014) retrospective cohort study of inpatients 18 years or older in a large, acute care teaching hospital composed of 16 wards, including 5 intensive care units and 11 non-intensive care unit wards.ExposuresPatient-level risk factors (eg, age, comorbidities, hospitalization history, antibiotic exposure) and ward-level risk factors (eg, antibiotic therapy per 100 patient-days, hand hygiene adherence, mean patient age) were identified from hospital databases.Main Outcomes And MeasuresIncidence of hospital-acquired C difficile infection as identified prospectively by hospital infection prevention and control staff.ResultsA total of 255 of 34 298 patients developed C difficile (incidence rate, 5.95 per 10,000 patient-days; 95% CI, 5.26-6.73). Ward-level antibiotic exposure varied from 21.7 to 56.4 days of therapy per 100 patient-days. Each 10% increase in ward-level antibiotic exposure was associated with a 2.1 per 10,000 (P < .001) increase in C difficile incidence. The association between C difficile incidence and ward antibiotic exposure was the same among patients with and without recent antibiotic exposure, and C difficile risk persisted after multilevel, multivariate adjustment for differences in patient-risk factors among wards (relative risk, 1.34 per 10% increase in days of therapy; 95% CI, 1.16-1.57).Conclusions And RelevanceAmong hospital inpatients, ward-level antibiotic prescribing is associated with a statistically significant and clinically relevant increase in C difficile risk that persists after adjustment for differences in patient-level antibiotic use and other patient- and ward-level risk factors. These data strongly support the use of antibiotic stewardship as a means of preventing C difficile infection.

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