Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines

Abstract

Background: In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective.

Methods: We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).

Results: Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy.

Conclusions: Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.

Keywords: Clostridioides difficile infection; Clostridium difficile infection; cost-effectiveness.

Figure 1.

State transition diagram of patient progression through initial Clostridioides difficile infection (CDI) and potential recurrences in the first 12 months. The states of final cure, postcolectomy cure, and death are absorbing states, as reflected by the self-loop arrows. Any patient who is alive at the end of the 12 months is assumed to have an average life expectancy with no further risk of CDI occurrence or CDI-related death. *Death from other causes.

Figure 2.

Available treatment options for Clostridioides difficile infection per Infectious Diseases Society of America guidelines. Abbreviations: CDI, Clostridioides difficile infection; FMT, fecal microbiota transplantation.

Figure 3.

Optimal strategy for treatment of Clostridioides difficile infection (CDI): fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for second and subsequent recurrence. Abbreviations: CDI, Clostridioides difficile infection; FMT, fecal microbiota transplantation.

Figure 4.

Cost-effectiveness acceptability curve for Clostridioides difficile infection (CDI) treatment strategies. Strategy 3 (orange) represents metronidazole for nonsevere initial CDI, and vancomycin for severe CDI and recurrent CDI. Strategy 37 (purple) represents vancomycin for all initial CDI and first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence. Strategy 43 (green) represents vancomycin for initial CDI (nonsevere and severe), fidaxomicin for first recurrence, and FMT for subsequent recurrence. Strategy 44 (red) represents fidaxomicin for initial nonsevere CDI and first recurrence, vancomycin for initial severe CDI, and FMT for subsequent recurrence. Strategy 47 (brown) represents fidaxomicin for all initial CDI and first recurrence, and FMT for subsequent recurrence. The black dashed curve highlights the cost-effectiveness frontier, which is the optimal strategy on average across all probabilistic sensitivity analysis samples. Strategy 44 is on the cost-effectiveness frontier above a willingness-to-pay threshold of $30 000 per quality-adjusted life-year (QALY).