{"title":"The Transmission of Clostridioides (Clostridium) difficile with a One Health Perspective.","authors":"Su-Chen Lim, Thomas V Riley","doi":"10.1016/j.idc.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.003","url":null,"abstract":"<p><p>Clostridioides difficile infection is a significant public health concern traditionally linked to health care settings. However, genomic evidence increasingly supports the spread of C difficile across humans, animals, food, and the environment with sources and reservoirs outside health care settings. Here, we review the transmission routes of C difficile within a One Health framework to uncover these complex interconnections. Understanding these pathways is essential for developing effective, integrated infection prevention and control strategies for health care and the community.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Changes in the Epidemiology of Clostridioides difficile Infection.","authors":"Alice Y Guh, L Clifford McDonald","doi":"10.1016/j.idc.2025.07.002","DOIUrl":"10.1016/j.idc.2025.07.002","url":null,"abstract":"<p><p>This article describes the epidemiology of Clostridioides difficile infection (CDI) by outlining common approaches to CDI surveillance, including the application of a case definition and risk adjustment, and summarizing recent global trends in the incidence or prevalence of CDI. The article also describes important risk factors for CDI and recent advancements in identifying sources of C difficile.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic Approaches for Clostridioides difficile Infection.","authors":"Parul Berry, Sahil Khanna","doi":"10.1016/j.idc.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.014","url":null,"abstract":"<p><p>This article offers a clinically focused overview of Clostridioides difficile infection (CDI) diagnosis, emphasizing the need to test only symptomatic patients and to distinguish true infection from colonization. It reviews multistep diagnostic algorithms that pair glutamate dehydrogenase (GDH) testing or nucleic acid amplification tests (NAAT) with toxin assays to improve accuracy. The limitations of PCR-only approaches are discussed, with a strong emphasis on clinical correlation. Guideline-based recommendations are integrated throughout, providing evidence-based direction for clinicians managing CDI in both inpatient and outpatient settings.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Understanding the Pathogenesis of Clostridioides difficile Infection.","authors":"Anna M Seekatz, Michael C Abt","doi":"10.1016/j.idc.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.001","url":null,"abstract":"<p><p>Clostridioides difficile infection (CDI) remains a significant cause of infectious colitis in the United States. Susceptibility to CDI is associated with perturbation of the gut microbiota, the indigenous microbes in the gastrointestinal tract. Upon colonization, the production of toxins and the ability to produce spores for environmental dissemination contribute to C difficile pathogenicity. Regulation of the virulence genes governing these processes are interconnected with C difficile metabolism and interactions with other gut microbes. This review summarizes these pathogenic aspects, with a focus on recent data illustrating additional mechanisms that modulate colonization and toxin-mediated disease during CDI development.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Predictive Modeling for Clostridioides difficile Infection: Current State of the Science, Clinical Applications, and Future Directions.","authors":"Krishna Rao, Jenna Wiens","doi":"10.1016/j.idc.2025.07.015","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.015","url":null,"abstract":"<p><p>Despite 2 decades of effort, there is a lack of clinically deployed models for predicting incident, severe, or recurrent Clostridioides difficile infection (CDI). This review outlines the promise of machine learning and biomarker-augmented models for targeted prevention and treatment, but also emphasizes the challenges of real-world deployment-namely integration into clinical workflows and governance. Moving forward, progress will depend on translational biomarker development, pragmatic modeling pipelines, and continuous monitoring. With these elements in place, CDI prediction tools can become a template for precision prevention of healthcare-associated infections.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Epidemiology of Clostridioidesdifficile.","authors":"Evan S Snitkin","doi":"10.1016/j.idc.2025.07.013","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.013","url":null,"abstract":"<p><p>Clostridioides difficile is the most common cause of health care-associated infections in the United States. The persistence of C difficile as a significant cause of morbidity and mortality is a testament to significant gaps remaining in our understanding of how and where it spreads, and pathways leading to disease. Over the past decade, the revolution in microbial whole-genome sequencing has enabled studies that have begun to fill in gaps in our understanding of C difficile. In this review, I will provide an overview of the contribution that genomics has made to our understanding of C difficile as a pathogen.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in the Medical Treatment of Clostridioides difficile Infection.","authors":"Nirja Mehta, Colleen Kraft, Stuart Johnson","doi":"10.1016/j.idc.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.005","url":null,"abstract":"<p><p>Clostridioides difficile medical management has changed significantly over the past decade with emphasis on preventing recurrent infection. This review compares current guidelines on the treatment of initial, recurrent, fulminant, and pediatric C difficile infection (CDI) and evaluates the mechanisms and clinical use of available antibiotics for CDI. C difficile has complex resistance mechanisms to vancomycin, fidaxomicin, and metronidazole which may play a role in treatment outcomes. Antibiotics such as tigecycline and rifaximin as well as monoclonal antibodies against toxin B may play a role in adjunctive therapy. Additional therapies under development include new narrow therapeutic antibiotics.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of Severe Clostridioides difficile Infection.","authors":"Jared Salrin, David B Stewart","doi":"10.1016/j.idc.2025.07.006","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.006","url":null,"abstract":"<p><p>Clostridioides difficile infection (CDI) severe enough to potentially require surgery represents a minority of patients with CDI. This cohort of individuals is characterized by severe sepsis with organ failure, despite the use of appropriate antibiotics directed against C difficile. In this article, a review of classification schemes for CDI severity is provided, and surgical treatment options (total colectomy vs diversion with a loop ileostomy and colonic lavage) are discussed. An overview of key principles for surgical consultation is also provided in an effort to both ensure that medical therapy is truly optimized while offering surgical intervention in a timely manner.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vitro and in Vivo Models for Understanding Clostridioides difficile.","authors":"Jennifer M Auchtung","doi":"10.1016/j.idc.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.009","url":null,"abstract":"<p><p>Several in vitro and in vivo models have been developed for characterizing Clostridioides difficile infection and disease. Syrian hamster and mouse models are the primary in vivo models of infection. Invertebrate animals and in vitro approaches can be used to model different steps of colonization and disease. In vitro models vary in complexity, with some facilitating high throughput screening under simple culture conditions and others reproducing more complex features of host-pathogen interactions. As no single model fully reproduces the disease spectrum in patients, optimal study design should integrate output from multiple, complementary models to inform our understanding of C. difficile.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rochelle C Glover, F Christopher Peritore-Galve, Borden Lacy, Joseph P Zackular
{"title":"Immune Aspects of Clostridioides difficile Infection and Vaccine Development.","authors":"Rochelle C Glover, F Christopher Peritore-Galve, Borden Lacy, Joseph P Zackular","doi":"10.1016/j.idc.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.idc.2025.07.008","url":null,"abstract":"<p><p>Clostridioides difficile causes antibiotic-associated diarrhea and pseudomembranous colitis. The pathogenesis of C difficile infection is driven by 2 exotoxins, TcdA and TcdB, making them priority targets for therapeutic intervention. Several vaccine formulations targeting these toxins have reached phase 3 clinical trials, but none have successfully prevented colonization or disease. Recent advances in understanding C difficile pathogenesis and vaccinology have revitalized efforts to develop an effective vaccine. Here, we discuss basic and clinical research insights to provide a framework for developing next-generation C difficile vaccines.</p>","PeriodicalId":13562,"journal":{"name":"Infectious disease clinics of North America","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}