By Richard R. Watkins, MD, MS, FACP, FIDSA

Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports that he has received research support from Allergan.

SYNOPSIS: The authors of a pharmacoeconomic study comparing bezlotoxumab plus oral vancomycin, oral vancomycin alone, and fidaxomicin found that oral vancomycin alone was the most cost-effective regimen to treat the first recurrence of Clostridium difficile infection.

SOURCE: Lam SW, Neuner EA, Fraser TG, et al. Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting. Infect Control Hosp Epidemiol 2018;39:924-930.

Approximately 10% to 30% of patients with Clostridium difficile infection (CDI) experience a recurrence, and the optimal management of recurrences is uncertain. Several different therapies are available, although data about their cost-effectiveness are limited. Therefore, Lam and colleagues sought to compare oral vancomycin, oral vancomycin plus bezlotoxumab, and fidaxomicin for cost-effectiveness to treat the first recurrence of CDI.

The study included data from randomized, controlled trials of outpatients who presented with their first episode of recurrent CDI. One of four treatment strategies was chosen: oral vancomycin every six hours for 10 days; fidaxomicin every 12 hours for 10 days; bezlotoxumab once plus oral vancomycin every six hours for 10 days; or a six-week oral vancomycin taper. The physician could choose to admit the patient for treatment, which did not affect the treatment strategy. Regardless of admission, patients were classified as cure or failure, the latter of which then were treated with an oral vancomycin taper, fecal microbial transplantation (FMT), or colectomy. The efficacy outcome was described in quality-adjusted life years (QALY), which ranges from 0 (death) to 1 (perfect health). The cost included direct costs, such as medications, hospitalizations, colectomy, FMT, and therapies for additional recurrences, and was viewed from the perspective of the payer. Indirect costs, such as loss of work, patient travel, and out-of-pocket expenses, were not included in the analysis.

Oral vancomycin alone involved the lowest cost and a QALY gain of 0.8019. Treatment with fidaxomicin had the second lowest cost and a QALY gain of 0.8046 over vancomycin alone. Bezlotoxumab plus vancomycin had the highest cost but also an incremental decrease in QALY. These findings demonstrated vancomycin alone to be the most cost-effective treatment because the incremental cost-effectiveness ratio (ICER) of fidaxomicin was > $100,000 per QALY gained. At a willingness-to-pay (WTP) threshold of $100,000 per QALY gained, vancomycin exhibited a probability of 68% as the most cost-effective, compared to 29% for fidaxomicin and 2.4% for bezlotoxumab plus vancomycin. When researchers increased the WTP threshold to $500,000 per QALY gained, oral vancomycin still was the most cost-effective therapy.


Recurrent CDI is a challenging condition for physicians to manage. Despite myriad treatment options, knowing which one will work best for an individual patient is difficult. The current Infectious Diseases Society of America (IDSA) guidelines for CDI recommend treating the first recurrence of CDI with either a tapered pulsed regimen of oral vancomycin (weak recommendation, low quality of evidence), a 10-day course of fidaxomicin (weak recommendation, moderate quality of evidence), or a 10-day course of vancomycin instead of a second metronidazole course if that drug was administered to treat the initial episode of infection (weak recommendation, low quality of evidence).1 Because it was not approved at the time, no recommendations about bezlotoxumab were made in the guidelines.

In addition to clinical efficacy, physicians also must weigh financial concerns when deciding on the treatment regimen. Thus, the study by Lam et al is welcome because it clarifies the cost-effectiveness of three widely used strategies for the first recurrence of CDI. It also is the first to evaluate bezlotoxumab in this setting. Although some previous studies showed a decrease in recurrences with fidaxomicin and bezlotoxumab compared to vancomycin, the authors of the present study found similar overall effectiveness with all three drugs. Although fidaxomicin had a slightly higher gain in QALY, its cost was well above the WTP threshold such that vancomycin alone emerged as the most cost-effective option.

The researchers did not include FMT as one of the treatment options in the study. This decision seems reasonable given that, in current clinical practice, FMT usually is reserved for patients with multiple recurrences and often after a vancomycin taper has failed. However, this strategy seems to be evolving, especially as the use of oral capsules becomes more commonplace.

The study had some notable limitations. First, the data were collected from randomized clinical trials and, therefore, the cure and recurrence rates may depict best-case scenarios and not real-world clinical settings. Second, the authors of the study did not take into account adverse events of the three treatment options. Third, differences in C. difficile strains were not considered. Thus, the cost-effectiveness results might not hold true when high toxin-producing strains (e.g., BI/NAP1/027) are prevalent. Finally, the investigators did not determine if there was a difference in the cost effectiveness between a six-week vancomycin taper and a 10-day course.

Currently, oral vancomycin, either as a 10-day course or a six-week taper, seems to be the most cost-effective approach for managing the first recurrence of CDI. As novel treatments become available, it will be important to conduct further pharmacoeconomic studies that compare multiple strategies in real-world settings.


  1. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018;66:e1-e48.