Review

Authors: Jacek Czepiel, Mirosław Dróżdż, Hanna Pituch...

Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Cross Infection; Diarrhea; Disease Reservoirs; Fecal Microbiota Transplantation; Feces; Humans; Risk Factors; Virulence

PubMed: 30945014
DOI: 10.1007/s10096-019-03539-6

Review

Authors: Stefano Di Bella, Gianfranco Sanson, Jacopo Monticelli...

SUMMARY infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for infection.

Topics: Humans; Clostridium Infections; Risk Factors; Clostridioides difficile; Cross Infection; Anti-Bacterial Agents; History, 21st Century

PubMed: 38421181
DOI: 10.1128/cmr.00135-23

Review

Authors: Kristin E Burke, J Thomas Lamont

Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices.

Topics: Asia; Clostridioides difficile; Clostridium Infections; Europe; Global Health; Humans; North America

PubMed: 24516694
DOI: 10.5009/gnl.2014.8.1.1

Review

Authors: Jung Hoon Song, You Sun Kim

The most common cause of antibiotic-associated diarrhea is infection (CDI). Recurrent infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Enterocolitis, Pseudomembranous; Fecal Microbiota Transplantation; Humans; Recurrence; Risk Factors; Secondary Prevention

PubMed: 30400734
DOI: 10.5009/gnl18071

Review

Authors: Jessica S H Martin, Tanya M Monaghan, Mark H Wilcox...

Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI.

Topics: Bacterial Typing Techniques; Clostridioides difficile; Clostridium Infections; Community-Acquired Infections; Cross Infection; Global Health; Humans

PubMed: 26956066
DOI: 10.1038/nrgastro.2016.25

Review

Authors: Michael Cymbal, Arjun Chatterjee, Brian Baggott...

Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and a significant impact on the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments such as Bezlotoxumab, fecal microbiota transplant, and live biotherapeutic products are proven effective in recurrent C. difficile infection and address dysbiosis.

Topics: Humans; Clostridium Infections; Anti-Bacterial Agents; Fecal Microbiota Transplantation; Clostridioides difficile; Antimicrobial Stewardship; Vancomycin; Fidaxomicin; Broadly Neutralizing Antibodies; Antibodies, Monoclonal

PubMed: 38508330
DOI: 10.1016/j.amjmed.2024.03.024

Review

Authors: Ramyavardhanee Chandrasekaran, D Borden Lacy

Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease.

Topics: Bacterial Toxins; Clostridioides difficile; Clostridium Infections; Humans; Immunity; Intestinal Mucosa

PubMed: 29048477
DOI: 10.1093/femsre/fux048

Review

Authors: Debbie-Ann Shirley, William Tornel, Cirle A Warren...

Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.

Topics: Adult; Child; Humans; Child, Preschool; Anti-Bacterial Agents; Clostridioides difficile; Vancomycin; Clostridium Infections; Diarrhea

PubMed: 37560802
DOI: 10.1542/peds.2023-062307

Review

Authors: Tamara Alhobayb, Matthew A Ciorba

PURPOSE OF REVIEW

The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients.

RECENT FINDINGS

CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children.

SUMMARY

Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.

Topics: Adult; Child; Humans; Clostridioides difficile; Recurrence; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Clostridium Infections; Fecal Microbiota Transplantation; Colonic Diseases

PubMed: 37265220
DOI: 10.1097/MOG.0000000000000949

Review

Authors: John E Markantonis, John T Fallon, Rajat Madan...

is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of , placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in , with an emphasis on CDI therapies.

Topics: Humans; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Diarrhea; Drug Resistance, Bacterial

PubMed: 38392856
DOI: 10.3390/pathogens13020118