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To assess changes in testing and treatment trends of CDI at a time when the Clostridium difficile hypervirulent strain was first identified.A retrospective cohort study was performed. C. difficile cytotoxicity results were merged with pharmacy databases and changes in testing and treatment pattern over time were assessed.6,613 tests for C. difficile were performed on 5,100 patients. Using least squares regression times series analysis, rates of testing increased by 0.63 ± 0.31 tests per month (P = 0.05) although the number of positive tests did not increase significantly. Overall, metronidazole was the most commonly used drug (81.6%), followed by vancomycin (9.3%), rifaximin (8.4%), and nitazoxanide (0.70%). Use of rifaximin increased by 3.3 ± 0.55 new prescriptions per month (Fig. 2; P < 0.01) while use of metronidazole increased by 5.0 ± 2.8 new prescriptions per month and oral vancomycin increased by 0.4 ± 0.7 new prescriptions per month; however these results were not statistically significant. For patients receiving rifaximin the drug was given as monotherapy (26.2%), in combination with oral vancomycin (24.2%), or in combination with metronidazole (49.7%).Increased rates of CDI testing and use of alternative therapies was observed at a time when the hypervirulent strain was first identified.