Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study

Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient's response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts. Keywords: Clostridioides difficile; mortality; outcomes; predictive factors; recurrence; severe infection; treatment

Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice

INTRODUCTION Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future

Les infections à streptococcus canis (étude rétrospective à partir de 54 souches diagnostiquées au CHU Bordeaux entre 1996 et 2002)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks

Introduction: The role of the gut microbiota in health and the pathogenesis of several diseases has been highlighted in recent years. Even though the precise mechanisms involving the microbiome in these ailments are still unclear, microbiota-modulating therapies have been developed. Fecal microbiota transplantation (FMT) has shown significant results against Clostridioides difficile infection (CDI), and its potential has been investigated for other diseases. Unfortunately, the technical aspects of the treatment make it difficult to implement. Pharmaceutical technology approaches to encapsulate microorganisms could play an important role in providing this treatment and render the treatment modalities easier to handle. Areas covered: After an overview of CDI, this narrative review aims to discuss the current formulations for FMT and specifically addresses the technical aspects of the treatment. This review also distinguishes itself by focusing on the hurdles and emphasizing the possible improvements using pharmaceutical technologies. Expert Opinion: FMT is an efficient treatment for recurrent CDI. However, its standardization is overlooked. The approach of industrial and hospital preparations of FMT are different, but both show promise in their respective methodologies. Novel FMT formulations could enable further research on dysbiotic diseases in the future.</p

Urinary Tract Infections in Older Men

International audienc

Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice

INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne’s FMT centre). RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future

Quality of life and utility decrement associated with Clostridium difficile infection in a French hospital setting

Abstract Background Clostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument. Methods A prospective study was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3 L was filled in by patients at 7 ± 2 days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed. Results Eighty patients were enrolled (mean age: 69.4 years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score ≥ 3) (p = 0.001), in patients with a positive baseline utility (p = 0.032), in women as compared to men (p = 0.041) and in patients aged more than 65 years (p = 0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053). Conclusions The impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration

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