Cost-Effectiveness Analysis of Five Competing Strategies for the Management of Multiple Recurrent Community-Onset <i>Clostridium difficile</i> Infection in France

<div><p>Background</p><p><i>Clostridium difficile</i> infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France.</p><p>Methods</p><p>We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses.</p><p>Results</p><p>Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY.</p><p>Conclusions</p><p>FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY.</p></div

Tornado diagram, FMT via enema versus pulsed-tapered vancomycin.

<p>Name of the variable (lower bound of the parameter—higher bound of the parameter [base case]). The ICER corresponding to the lower parameter bound is shown in black, while the ICER corresponding to the higher parameter bound is shown in grey. This figure represents the impact of the uncertainty of six parameters on the base case results. Abbreviations: CDI: <i>Clostridium difficile</i> infection; FMT: fecal microbiota transplantation; ICER: incremental cost-effectiveness ratio.</p

Base case analysis of competing strategies for the management of second recurrence of community-onset <i>Clostridium difficile</i> infection.

<p>Base case analysis of competing strategies for the management of second recurrence of community-onset <i>Clostridium difficile</i> infection.</p

Decision tree comparing 5 strategies for the treatment of second recurrence of community-onset <i>Clostridium difficile</i> infection.

<p>Note: expanded model details shown for vancomycin pulse/taper arm only. Abbreviations: CDI: <i>Clostridium difficile</i> infection; FMT: fecal microbiota transplantation.</p

Acceptability curve of treatments of second recurrence of <i>Clostridium difficile</i> infection.

<p>This figure illustrates the proportion of the time each treatment was cost-effective at different willingness-to-pay thresholds. Abbreviations: FMT: fecal microbiota transplantation.</p

Base case estimates, range, and distribution for model variables.

<p>Base case estimates, range, and distribution for model variables.</p

Additional file 1 of Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort

Additional file 1: Figure S1. Flow chart of the study. Figure S2. Alpha diversity changes over time in ventilated and non-ventilated groups. Figure S3. Jaccard beta-diversity of ventilated and non-ventilated patients at day 0 depicted on NMDS

Additional file 2 of Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort

Additional file 2: Table S1. Demographic characteristics of participants based on the ventilatory status in the COVID-19 cohort. Table S2. COVID-19 symptoms, status and treatment of participants based on the ventilatory status in the COVID-19 cohort. Table S3. Risk factors of COVID-19 infected participants. Table S4. Demographic characteristics of Non-COVID-19 ventilated patients. Table S5. Nutrition characteristics of the patients