Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States and is associated with considerable morbidity [1]. There has also been an increase in the incidence and severity of CDI, and recognition of how community-acquired CDI contributes to the healthcare burden [2]. The economic costs of CDI exceeds $1 billion annually in the United States, with a similarly high burden in Europe [3, 4]. Contributing to this is the substantial risk of recurrent CDI. One-third of patients with CDI experience recurrent disease despite a primary cure; this proportion rises to two-thirds after the first episode of recurrence. The consequences of recurrent CDI are compounded by the fact that in patients at the highest risk of recurrent disease, risk factors for recurrence remain impossible (age, comorbidity) or difficult to modify (continued hospitalization or long-term-care facility stay, ongoing antibiotic use). Thus, identification of appropriate strategies to manage recurrent CDI is an important goal. Our armamentarium for management of CDI and disease recurrence has increased. Both metronidazole and vancomycin are associated with substantial rates of recurrent disease [2]. Fidaxomicin promises reduced rates of recurrence, but its high cost has prohibited more widespread use [5, 6]. Other nonpharmacologic therapeutic approaches have emerged. Fecal microbiota transplant (FMT), involving luminal infusion of feces from a healthy donor to a patient, is highly effective for recurrent CDI [7–11]. FMT shows extraordinary clinical resolution rates with very low rates of recurrence, suggesting that the restoration of microflora diversity may surpass the efficacy of conventional therapy. However, the lack of comparative effectiveness studies and long-term follow-up preclude development of an optimal cost-effective treatment algorithm at a societal level. The cost-effectiveness of a therapeutic strategy depends both on treatment-associated costs and health and cost benefits through prevention of future recurrences. A prior cost-utility analysis comparing fidaxomicin and vancomycin for the treatment of an initial episode of CDI or first recurrence suggested that fidaxomicin might be a cost-effective option under a few clinical scenarios [12]. However, there were several limitations to this analysis, including lack of a range of options for the treatment of recurrence and exclusion of promising therapies such as FMT. To date, there have been no comprehensive decision analytic models examining the optimal management of recurrent CDI that include FMT; this would be an important tool to inform clinical practice given the expanding spectrum of treatment options and increasing physician and patient interest. Thus, the aim of our study was to analyze the cost effectiveness of 4 competing strategies for the management of recurrent CDI where the first-line treatments were metronidazole, vancomycin, fidaxomicin, or FMT. We performed various sensitivity analyses to mimic relevant clinical scenarios across a range of efficacy and costs, and suggest optimal thresholds for future therapies to be cost-effective.