Infection Prevention Approaches for Clostridioides difficile
Clostridioides difficile prevention is challenging as spores are highly resilient and transmission sources diverse. Hand hygiene, contact precautions, and environmental decontamination are fundamental infection prevention strategies. Antimicrobial stewardship is highly effective at reducing C difficile risk at both the individual and institutional level. Supplemental control measures such as no-touch disinfection technologies and screening/isolation of carriers are generally reserved for situations in which fundamental control measures prove insufficient. Reducing host vulnerability through immunization, prophylactic antibiotics directed against C difficile, or products that protect/augment the microbiome may offer promise in the future.
Clostridioides difficile in Children
After a significant increase in pediatric Clostridioides difficile infection (CDI) in the United States over the past 2 decades, incidence has declined over the past 5 y. Community-associated CDI incidence is 3 times higher than healthcare facility-associated CDI in children, but sources of community acquisition are poorly defined. Diagnosis of CDI is challenging because of high frequency of colonization in infants and some groups of older children. Recent data suggest that vancomycin should be considered a first-line treatment for CDI in children and that fidaxomicin and fecal microbiota transplantation are safe and effective therapies for recurrent CDI.
Microbiome Therapeutics for Clostridioides difficile Infection
Microbiota-based therapies are used increasingly for the treatment and prevention of Clostridioides difficile infection (CDI), particularly in cases of recurrent CDI (rCDI). This review discusses the different types of microbiota-based therapies, including fecal microbiota transplant, fecal microbiota products, and live biotherapeutic products. The authors present efficacy data regarding clinical use in rCDI and highlight the unique aspects of each product.
Making Sense of Differing Guidelines for Clostridioides difficile Infection
The Clostridioides difficile infection (CDI) epidemic has been impacting the world for years. Understanding accurate diagnostics is imperative to allow the appropriate patients to be treated and improve outcomes. This article leverages multiple global societal guidelines to focus on the evolving diagnostic tests available summarizing best diagnostic practices including 2-step diagnostic testing. Therapeutically, guideline recommendations more recently have favored fidaxomicin and incorporated immune-based therapies and microbial restoration therapies. As treatment options and guideline recommendations change, it is imperative to understand why these recommendations have evolved and understand current best diagnostic and therapeutic practices in managing CDI.
Immune Aspects of Clostridioides difficile Infection and Vaccine Development
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.
The Transmission of Clostridioides (Clostridium) difficile with a One Health Perspective
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.
Advances in the Medical Treatment of Clostridioides difficile Infection
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.
Management of Severe Clostridioides difficile Infection
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.
Predictive Modeling for Clostridioides difficile Infection: Current State of the Science, Clinical Applications, and Future Directions
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.
Genomic Epidemiology of Clostridioidesdifficile
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.
Changes in the Epidemiology of Clostridioides difficile Infection
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.
Diagnostic Approaches for Clostridioides difficile Infection
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.
Advances in Understanding the Pathogenesis of Clostridioides difficile Infection
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.
Clostridioides difficile Infection: Advances and New Challenges
In vitro and in Vivo Models for Understanding Clostridioides difficile
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.
Navigating the Challenges in Staphylococcus aureus Bloodstream Infection: A Practical Guide to Management
Staphylococcus aureus bacteremia (SAB) continues to challenge clinicians with its' diverse clinical presentations, risk of complications, and high mortality rate. While foundational principles of management, such as adequate source control and appropriate antibiotic treatment, remain unchanged, the landscape is evolving for both diagnostic and treatment strategies. This review explores emerging evidence; outlines current best practice in diagnosis, risk stratification, and treatment; and highlights ongoing controversies and limitations of traditional management paradigms. Given the marked clinical heterogeneity of SAB, advancing toward a personalized medicine approach that tailors management to patient and pathogen characteristics is an important goal for the field.
Local Antibiotic Delivery in Orthopedics: Review of Current Practices and Emerging Technologies
This article explores the role of local antibiotic delivery in the management of orthopedic infections, a significant challenge in modern healthcare. This article delineates between prophylactic and therapeutic uses of antibiotics, examining various delivery methods, including topical powders, irrigation solutions, intraosseous injections, and antibiotic-loaded bone cement. While local administration aims to enhance therapeutic efficacy and minimize systemic exposure, there is limited evidence supporting effectiveness. The article aims to review the current practices and evidence and highlight emerging strategies such as hydrogels and biodegradable systems. Ongoing research is essential to optimize these methods and improve patient outcomes in orthopedic care.
Periprosthetic Joint Infections
Periprosthetic joint infection (PJI) is a dreaded and devastating complication of total joint arthroplasty. The clinical presentation of PJI is dependent on multiple factors, but typically involves pain, swelling, warmth and erythema of the affected joint. The management of PJI is complex, with both the medical and surgical approach being scenario specific. The importance of interdisciplinary collaboration to manage these complicated infections cannot be overstated. This review, aimed at the practicing infectious diseases clinician, details the background, microbiology, clinical presentation, diagnosis and both surgical and medical treatment of PJI.
Orthopedic Device Infections in Children
Orthopedic device infections in children are complicated and diverse, often affecting patients with concomitant conditions such as neuromuscular disorders or solid tumors. As such, diagnosis and management of these infections is personalized, nuanced, and specialized. In this review, we focus on infections related to spinal hardware and prostheses inserted during limb-salvage surgery for bone tumors. Important differences from adults in patient characteristics, epidemiology, and management requirements make it important to understand specific aspects of these infections in pediatric patients to optimize patient care and outcomes.
Jaw Osteomyelitis
Mandibular osteomyelitis is caused most commonly by members of the oral flora in the setting of dental infection or dental manipulation, often in patients with underlying mandible pathology. Recognizing and treating mandible infections is especially challenging when they are associated with osteonecrotic conditions that are themselves difficult to manage and that may be associated with symptoms and testing results that mimic infection. Optimized diagnosis and management of mandible infections require collaboration between specialists in surgical and medical aspects of care, with the goal of clearing or controlling infection while maximizing function.
Native Joint Septic Arthritis
Native joint septic arthritis is an infectious condition requiring timely diagnosis and management to prevent irreversible joint damage. This article aims to provide a comprehensive overview of septic arthritis, focusing on pathogenesis, epidemiology, clinical presentation, diagnostic approaches, and treatment strategies.
