Antibiotic Stewardship and Clostridium difficile–Associated Disease

To the Editor—In the past 2 decades, Clostridium difficile has emerged as a major cause of nosocomial infection,' largely facilitated by antibiotic use, much of which is excessive and/ or unnecessary. We applied recently described case definitions of G di^jri/e-associated disease (CDAD) to document the beneficial effects of an antibiotic stewardship program. Beginning January 1, 2001, we tracked every case of CDAD at our 550-bed teaching hospital. Despite continued emphasis on handwashing and isolation procedures, the incidence of CDAD remained constant during the period from October 2003 through August 2006 (Figure). In September 2006, we instituted an antibiotic stewardship program, under which prescriptions for most parenteral antibiotics required approval by an infectious disease physician or clinical pharmacist. Penicillin, ampicillin, ampicillin-sulbactam, nafcillin, ceftriaxone, aztreonam, aminoglycosides, metronidazole, and oral formulations of antimicrobial agents could be ordered without approval; daytime orders for all other antibiotics were only honored if approved. Nighttime orders for formulary antibiotics were honored until 7:30 AM the following day, when the pharmacist and infectious diseases physician reviewed them, either approving the order or contacting a resident to make other recommendations. Antibiotic prophylaxis before surgery was not addressed, although continuation of such treatment after 48 hours required approval through the antibiotic stewardship program. Beginning February 2007, we applied Centers for Disease Control and Prevention case definitions of CDAD retroactively to 2003 and prospectively. CDAD was defined as a diarrheal disease (loose or watery stools generally 3 or more times per day) and/or an abdominal discomfort with a positive result of an enzyme-linked immunosorbent assay (ELISA) for C. difficile toxins A and B (Premier Toxins A&B EIA; Meridian Bioscience). A new case of CDAD was diagnosed if a patient met the case definition and had not had a diagnosis of this disease any time in the preceding 8 weeks. Recurrent disease was considered to be present if symptoms reappeared 2-8 weeks after the initial assay result was found to be positive for C. difficile toxin in a patient who had responded to therapy. A patient with continuous symptoms and repeated positive test results was considered to have a single case. The total number of cases equals the sum of new and recurrent cases. For the 3 years preceding the introduction of the antibiotic stewardship program, the mean incidence of all cases of CDAD was 41.7 cases per month (3.3 cases per 1,000 beddays) (Figure). Implementation of the program was followed by a decline to 22.0 cases per month (1.7 cases per 1,000 beddays) during the ensuing 12 months, a 47.2% decrease (P< .001, by ttest). The mean incidence of first-time CDAD, which we defined as a documented case of CDAD in a patient who had never previously had this disease, was 28.4 cases per month (2.2 cases per 1,000 bed-days) before implementation of the antibiotic stewardship program and 16.4 cases per month (1.2 cases per 1,000 bed-days) after, a 42.2% decrease (P<.001). These data show that implementation of a hospital-wide