Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection

Background: Previous observations have indicated that infection with Clostridium difficile occurs almost exclusively after exposure to antibiotics, but more recent observations have suggested that prior antibiotic exposure may be less frequent among cases of community-acquired disease. Methods: We used 2 linked health databases to perform a matched, nested case-control study of elderly patients admitted to hospital with community-acquired C. difficile infection. For each of 836 cases among people 65 years of age or older, we selected 10 controls. We determined the proportion of cases that occurred without prior antibiotic exposure and estimated the risk related to exposure to different antibiotics and the duration of increased risk. Results: Of the 836 cases, 442 (52.9%) had no exposure to antibiotics in the 45-day period before the index date, and 382 (45.7%) had no exposure in the 90-day period before the index date. Antibiotic exposure was associated with a rate ratio (RR) of 10.6 (95% confidence interval [CI] 8.9-12.8). Clindamycin (RR 31.8, 95% CI 17.6-57.6), cephalosporins (RR 14.9, 95% CI 10.9-20.3) and gatifloxacin (RR 16.7, 95% CI 8.3-33.6) were associated with the highest risk. The RR for C. difficile infection associated with antibiotic exposure declined from 15.4 (95% CI 12.2-19.3) by about 20 days after exposure to 3.2 (95% CI 2.0-5.0) after 45 days. Use of a proton pump inhibitor was associated with increased risk (RR 1.6, 95% CI 1.3-2.0), as were concurrent diagnoses of inflammatory bowel disease (RR 4.1, 95% CI 2.6-6.6), irritable bowel syndrome (RR 3.4, 95% CI 2.3-5.0) and renal failure (RR 1.7, 95% CI 1.2-2.2). Interpretation: Community-acquired C. difficile infection occurred in a substantial proportion of individuals with no recent exposure to antibiotics. Among patients who had been exposed to antibiotics, the risk declined markedly by 45 days after discontinuation of use.