A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies

Fidaxomicin to prevent recurrent

IMPORTANCE: Recent changes in guidelines for managing OBJECTIVE: To estimate the net cost of first-line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving for the prevention of recurrence. DATA SOURCES AND STUDY SELECTION: We identified randomized, placebo-controlled trials directly comparing fidaxomicin with vancomycin that reported on recurrence. Medication costs were obtained from the Veterans Affairs Federal Supply Schedule (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country. DATA EXTRACTION SYNTHESIS AND OUTCOME MEASURES: For efficacy, data on CDI recurrence at day 40 were pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect May 2022 dollars. These were used to estimate the net cost per recurrence prevented with fidaxomicin and the price point below which fidaxomicin would be cost saving. RESULTS: The estimated mean system costs of a CDI recurrence were $15 147USD and$8806CAD, respectively. Preventing one recurrence by using first-line fidaxomicin over vancomycin would cost $38 222USD (95$30 577-$57 332) and$13 760CAD (95%CI $11 008-$20 640), respectively. The probability that fidaxomicin was cost saving exceeded 95% if priced below $1140USD or$860CAD, respectively. CONCLUSIONS AND RELEVANCE: An increased drug expenditure on fidaxomicin may not be offset through recurrence prevention unless the fidaxomicin price is negotiated

Real-world evidence of sotrovimab effectiveness for preventing severe outcomes in patients with COVID-19: A quality improvement propensity-matched retrospective cohort study of a pan-provincial program in Alberta, Canada

Objectives: Post-marketing surveillance of sotrovimab's effect during implementation in the Canadian population is limited. Methods: The study used a propensity score–matched retrospective cohort design. Follow-up began between the periods of December 15, 2021 and April 30 2022. The study assessed any severe outcome defined as all-cause hospital admission or mortality within 30 days of a confirmed COVID-19–positive test. Covariate-adjusted odds ratios between sotrovimab treatment and the severe outcome was conducted using logistic regression. Results: There were 22,289 individuals meeting the treatment criteria for sotrovimab. There were 1603 treated and 6299 untreated individuals included in the analysis. The outcome occurrence in the study was 5.49% (treated) and 4.21% (untreated), with a median time from diagnosis to treatment of 1.00 days (interquartile range 2.00 days). In the propensity-matched cohort, sotrovimab was not associated with lower odds of a severe outcome (odds ratio 1.20, 95% confidence interval 0.91-1.58), adjusting for confounding variables. Conclusions: After adjusting for confounding variables, sotrovimab treatment was not associated with lower odds of a severe outcome within 30-days of COVID-19–positive date