Recurrent Clostridioides difficile infection remains common despite optimized antibiotic therapy. Two Food and Drug Administration-approved donor-derived fecal microbiota-based products, fecal microbiota, live-jslm (Rebyota / RBL) and fecal microbiota spores, live-brpk (Vowst / VOS) reduce recurrence when administered after completion of standard antibiotics. This review summarizes the clinical development programs supporting these products, including pivotal randomized trials, open-label extensions, durability data, safety outcomes, and emerging real-world evidence. We also discuss patient selection, timing after antibiotics, diagnostic considerations, and practical implementation. These therapies represent standardized, evidence-based approaches to restoring colonization resistance and preventing recurrent infection in appropriately selected adults.
Clostridium difficile infection (CDI) is classified as non-severe, severe, or fulminant based on clinical severity and presence of complications. Clinical manifestations span a broad spectrum, ranging from mild self-limited diarrhea to severe colonic inflammation with potentially fatal outcomes. Management strategies for CDI are guided by this severity-based classification. In this article, the authors focus on non-severe CDI, reviewing its definition, diagnostic approach, prevention strategies, treatment options, and predictors of treatment failure. They conclude by highlighting emerging areas of research and future directions in the management of non-severe CDI.
Clostridioides difficile infection (CDI) is a leading healthcare-associated illness with significant recurrence rates and clinical burden. Recurrent CDI (rCDI) arises from microbiota disruption, often exacerbated by antibiotic therapy. Current treatment strategies include fidaxomicin and vancomycin taper regimens, with adjunctive options such as rifaximin in select cases. Preventive approaches focus on environmental decontamination and microbiome preservation. Emerging therapies, including live biotherapeutics, non-toxigenic strains, and microbiome-protective agents, show promise in reducing recurrence. Dietary interventions that enhance microbial diversity may also support recovery. Together, these strategies highlight a shift toward microbiome-centered management of rCDI.
Clostridioides difficile infection (CDI) epidemiology has evolved over the past 3 decades. In the early 2000s, incidence and severity surged, driven by hypervirulent strains, extensive use of broad-spectrum antibiotics, an aging population, suboptimal infection-control practices, and highly sensitive molecular diagnostics. During the same period, community-associated CDI (CA-CDI) emerged affecting a different population. Recent optimization of infection prevention, antimicrobial stewardship, and multi-step diagnostic algorithms have helped curb hospital-acquired CDI. However, CA-CDI accounts for approximately half of all CDI cases and is rising. These trends underscore the need for continued surveillance, targeted prevention strategies, and enhanced access to effective treatments.
Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infectious diarrhea, often triggered by disruption of the gut microbiota. Recurrence is common after antibiotic treatment, prompting interest in microbial therapies such as probiotics. While some studies suggest probiotics may help prevent initial or recurrent CDI episodes, overall evidence remains inconsistent. Data on prebiotics and synbiotics are even more limited. Although generally safe, probiotics may delay restoration of the normal microbiome, which is key to preventing recurrence. Current guidelines vary from cautious support to discouragement of their use, leaving the role of these therapies in CDI management uncertain and investigational.
Clostridioides difficile infection (CDI) continues to be a challenging issue for health care providers and place a heavy burden on health care facilities. The prevention of community-acquired and healthcare-acquired CDI rests on reducing the person-level risk factors (most commonly exposure to antibiotics and reducing the disruption of the normally protective intestinal microbiota). Prevention of facility-level CDI rests on multifaceted infection control practices that include antibiotic stewardship programs, prompt diagnosis and isolation of CDI cases, environmental disinfection and cleaning, and training of multidisciplinary teams. Use of probiotics of specific strains in high-risk patients is worthy of future investigation.
Clostridioides difficile is a gram-positive bacterium and major cause of infectious colitis, in hospital and health care settings, where it remains a significant public health threat. Accurate diagnosis of C difficile infection (CDI) is challenging and requires a clinical assessment supported by laboratory stool testing. Reliance on laboratory tests can lead to both overdiagnosis and underdiagnosis. This article outlines the pathophysiology of C difficile, with emphasis on aspects related to diagnostic testing, and discusses the clinical approach to clinical diagnosis. New therapies for the treatment and prevention of CDI all rely on accurate clinical and laboratory identification of true infection.
This article synthesizes the evidence supporting fecal microbiota transplantation (FMT) as a paradigm-shifting therapy for recurrent Clostridioides difficile infection (rCDI), highlighting the mechanisms, clinical efficacy across populations, and delivery methods. FMT has been shown to increase gut microbial diversity, restore bile acid metabolism, and induce resistance against colonization, resulting in the treatment of rCDI. Randomized controlled trials and meta-analyses of real-world data demonstrate clinical resolution rates of 85% to 90%, with higher cure rates observed after multiple FMTs. We further examine predictors of FMT failure and outcomes in special populations, underscoring the safety and efficacy of FMT in high-risk patients.
Clostridioides difficile is a gram-positive, anaerobic bacteria that is ubiquitous. Oral-fecal transmission of the organism and its spores leads to C difficile colonization and infection (CDI) within the human gastrointestinal tract. Patients with inflammatory bowel disease (IBD) are more likely to be colonized with C difficile, develop CDI, and experience recurrence when compared to the general population. The biggest challenge of managing CDI in IBD remains diagnostic uncertainty and relies on clinicians' judgment.
Severe and fulminant Clostridioides difficile infection (CDI) represent distinct clinical entities that portend poor outcomes and require close monitoring and multidisciplinary management. Early recognition is key, and CDI-directed antimicrobials are the mainstay of therapy. If patients fail to improve despite maximal medical therapy, fecal microbiota transplantation (FMT) or surgical intervention should be considered. If FMT is performed, repeated dosing is often required. Surgical interventions such as colectomy or loop ileostomy are necessary in FMT nonresponders or those who have developed a complication such as perforation.
Due to the small number of intestinal transplant patients and the limited number of intestinal transplant centers, there is limited data available for consensus for best practices in terms of clinical follow-up after transplantation. As a result, there is a need to highlight the expected patient presentation and potential complications that may present after an intestinal transplant. Additionally, the current practices for postintestinal transplant patients in the clinical setting should be summarized in a clear manner with the goal of continuing practices that prove beneficial and strengthening the postintestinal transplant regimen while also highlighting areas that are still under development.
