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We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P ‫؍‬ 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly as- C lostridium difficile infection (CDI) has been increasing in both severity and incidence (1, 2). In 2011, it was associated with an estimated 29,000 deaths in the United States alone (1). The current mainstays of therapy, metronidazole and oral vancomycin, have been used in CDI therapy for over 30 years with very little drug resistance seen (3). Current guidelines for the treatment of CDI recommend metronidazole for mild to moderate infection and vancomycin for severe infection or recurrent episodes (3, 4). Recent data have challenged the positioning of these drugs for CDI therapy, as oral vancomycin was superior to metronidazole in a study comparing the two drugs and tolevamer, a toxin-binding agent that did not fair well in the study (5).Recently, fidaxomicin, a nonabsorbed macrolide antibiotic, was studied for the treatment of CDI and was found to be superior to oral vancomycin for the prevention of recurrences of CDI (6, 7). Cost concerns and a lack of updated guidelines for CDI may have prevented uptake of fidaxomicin by hospital and managedcare formularies, decreasing its utilization. However, CDI treatment is itself expensive, and if the use of fidaxomicin could prevent readmissions, it is possible that the increased clinical benefits would correlate with decreased costs. To achieve these ends, we instituted a guideline that recommended fidaxomicin as a firstline agent for treatment of many patients with CDI. This study evaluated the outcomes, costs, and costs avoided associated with the use of vancomycin and fidaxomicin after the implementation of this policy. MATERIALS AND METHODSThis was a single-center retrospective study of adult patients who received oral vancomycin or fidaxomicin for CDI treatment from January 2012 to January 2014. A protocol was established encouraging fidaxomicin use for selected patients (Fig. 1). All patients included in this study were eligible for fidaxomicin therapy by the terms of the protocol. The dose recommended by the protocol was 200 mg administered orally twice daily.Inclusi...