Abstract:Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this n… Show more
“… 137 Similar analyses advocating for bezlotoxumab have been performed and yet pharmacy budgets have not been increased to account for inpatient use and payors continue to impede prescribing it without prior authorization. 138 , 139 Whether an increased number of therapeutic options for rCDI will influence the costs of existing agents on the market remains to be seen. Ultimately, the choice of LBP selected for rCDI prevention will depend on patient preference, prescriber opinion, and cost.…”
Section: Clinical Trials Of the Fda Approved Lbps (Rebyota And Vowst)mentioning
Clostridioides difficile
infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond
C. difficile
.
“… 137 Similar analyses advocating for bezlotoxumab have been performed and yet pharmacy budgets have not been increased to account for inpatient use and payors continue to impede prescribing it without prior authorization. 138 , 139 Whether an increased number of therapeutic options for rCDI will influence the costs of existing agents on the market remains to be seen. Ultimately, the choice of LBP selected for rCDI prevention will depend on patient preference, prescriber opinion, and cost.…”
Section: Clinical Trials Of the Fda Approved Lbps (Rebyota And Vowst)mentioning
Clostridioides difficile
infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond
C. difficile
.
“…These methods are considered the gold standard to differentiate C. difficile RTs. They are highly informative, but also time-consuming (48-96h respectively from bacterial culture) and labor-intensive, requesting highly trained personnel and specific instruments, both factors lacking in most diagnostic laboratories (Bidet, Lalande, et al 2000; Abad-Fau, Sevilla et al 2023). The Xpert ® C. difficile BT assay has been implemented worldwide for the rapid differentiation of toxigenic C. difficile strains (Bai, Hao et al 2021).…”
Clostridioides difficile is a major cause of hospital-acquired diarrhea, posing significant clinical challenges due to its high mortality rates and its involvement in nosocomial outbreaks. Detecting its toxigenic ribotypes (RTs) rapidly and accurately is crucial for effective management and preventing fatal outcomes. This research aimed to create a methodology based on MALDI-TOF MS and Machine Learning (ML) algorithms to differentiate C. difficile RTs. MALDI-TOF spectra were acquired from 363 clinical isolates sourcing from 10 Spanish hospitals and analysed using Clover MSDAS and AutoCdiff, an ad hoc software developed in this study. Experiments confirmed seven biomarker peaks differentiating RT027 and RT181 from other RTs. Automatic classification tools in Clover MSDAS and AutoCdiff showed up to 100% balanced accuracy, even for isolates from real-time outbreaks. The developed models, available on the AutoCdiff website -https://bacteria.id-, offer researchers a valuable tool for quick RT determination. This approach significantly reduces time, costs, and hands-on time.
“…Common therapy for CDI includes antibiotics such as metronidazole for mild cases and vancomycin or fidaxomicin for moderate to severe cases 6 . Therapies with the human antibody bezlotoxumab against C. difficile toxin B or Fecal Microbiota Transplant (FMT) to restore the balance of the microbiome have been recommended to treat or prevent recurrences 7,8 .…”
Clostridioides difficile stands as the leading cause of hospital acquired enteric infection in developed countries. In Argentina, the epidemiology of Clostridioides difficile infection (CDI) is currently poorly characterized. Therefore, we conducted a retrospective case-control study evaluating the prevalence of CDI in 249 stool samples collected between 2019 and 2023 in the Northwest region of Buenos Aires. The presence of C. difficile was detected by combining three techniques (EIA, PCR and toxigenic culture) in a diagnostic algorithm. Clinical and demographic data from patients was also analyzed to identify CDI-associated risk factors. 1 in 5 patients presented C. difficile as the etiological agent of diarrhea and the 80% of CDI+ cases carried toxigenic strains, most of which had been acquired in the community. Age ≥69 years, previous use of antibiotics, previous hospitalization and previous episodes of CDI emerged as predisposing factors for CDI in our study cohort. Blood parameters such as an elevated number of leukocytes and platelets, a decreased basophil count, and an increased urea concentration were identified as indicators of CDI. We also carried out a systematic review and a meta-analysis where we contrasted our results with 39 studies selected from different countries around the world. At the global level, the meta-analysis highlighted advanced age, previous consumption of antibiotics and previous hospitalization as CDI risk factors and the leukocyte count as an indicator of CDI. These results emphasize the importance of epidemiological studies and reveal crucial information for healthcare decision-making regarding CDI.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.