-
Gut and Liver Jan 2014Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced... (Review)
Review
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 -
Clinical Microbiology and Infection :... Jul 2020For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt... (Review)
Review
BACKGROUND
For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt the microbiota of the gastrointestinal tract. Previously, it was thought that C. difficile was primarily a hospital-acquired infection; however, with the emergence of community-associated cases, and whole-genome sequencing suggesting the majority of the hospital C. difficile infection (CDI) cases are genetically distinct from one another, there is compelling evidence that sources/reservoirs of C. difficile outside hospitals play a significant role in the transmission of CDI.
OBJECTIVES
To review the 'One Health' aspects of CDI, focusing on how community sources/reservoirs might be acting as a conduit in the transfer of C. difficile between animals and humans. The importance of a One Health approach in managing CDI is discussed.
SOURCES
A literature search was performed on PubMed and Web of Science for relevant papers published from 1 January 2000 to 10 July 2019.
CONTENT
We present evidence that demonstrates transmission of C. difficile in hospitals from asymptomatic carriers to symptomatic CDI patients. The source of colonization is most probably community reservoirs, such as foods and the environment, where toxigenic C. difficile strains have frequently been isolated. With high-resolution genomic sequencing, the transmission of C. difficile between animals and humans can be demonstrated, despite a clear epidemiological link often being absent. The ways in which C. difficile from animals and humans can disseminate through foods and the environment are discussed, and an interconnected transmission pathway for C. difficile involving food animals, humans and the environment is presented.
IMPLICATIONS
Clostridium difficile is a well-established pathogen of both humans and animals that contaminates foods and the environment. To manage CDI, a One Health approach with the collaboration of clinicians, veterinarians, environmentalists and policy-makers is paramount.
Topics: Animals; Carrier State; Clostridioides difficile; Clostridium Infections; Community-Acquired Infections; Cross Infection; Environmental Microbiology; Food Microbiology; Genome, Bacterial; Humans; One Health; Whole Genome Sequencing
PubMed: 31682985
DOI: 10.1016/j.cmi.2019.10.023 -
Nature Oct 2010Clostridium difficile infection is the leading cause of healthcare-associated diarrhoea in Europe and North America. During infection, C. difficile produces two key...
Clostridium difficile infection is the leading cause of healthcare-associated diarrhoea in Europe and North America. During infection, C. difficile produces two key virulence determinants, toxin A and toxin B. Experiments with purified toxins have indicated that toxin A alone is able to evoke the symptoms of C. difficile infection, but toxin B is unable to do so unless it is mixed with toxin A or there is prior damage to the gut mucosa. However, a recent study indicated that toxin B is essential for C. difficile virulence and that a strain producing toxin A alone was avirulent. This creates a paradox over the individual importance of toxin A and toxin B. Here we show that isogenic mutants of C. difficile producing either toxin A or toxin B alone can cause fulminant disease in the hamster model of infection. By using a gene knockout system to inactivate the toxin genes permanently, we found that C. difficile producing either one or both toxins showed cytotoxic activity in vitro that translated directly into virulence in vivo. Furthermore, by constructing the first ever double-mutant strain of C. difficile, in which both toxin genes were inactivated, we were able to completely attenuate virulence. Our findings re-establish the importance of both toxin A and toxin B and highlight the need to continue to consider both toxins in the development of diagnostic tests and effective countermeasures against C. difficile.
Topics: Animals; Antibodies, Neutralizing; Bacterial Toxins; Chlorocebus aethiops; Clostridioides difficile; Clostridium Infections; Cricetinae; Disease Models, Animal; Enterotoxins; Gene Deletion; HT29 Cells; Humans; Neutralization Tests; Vero Cells; Virulence
PubMed: 20844489
DOI: 10.1038/nature09397 -
Clinical Microbiology and Infection :... Aug 2016In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was...
In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage.
Topics: Algorithms; Bacterial Toxins; Clostridioides difficile; Clostridium Infections; DNA, Bacterial; Early Diagnosis; European Union; Humans; Population Surveillance; Practice Guidelines as Topic; Reagent Kits, Diagnostic; Sensitivity and Specificity; Societies, Medical
PubMed: 27460910
DOI: 10.1016/j.cmi.2016.03.010 -
Clinics in Laboratory Medicine Mar 2010Clostridium difficile has re-emerged as a major hospital-acquired infection since 2001. Despite development of polymerase chain reaction-based testing, no single... (Review)
Review
Clostridium difficile has re-emerged as a major hospital-acquired infection since 2001. Despite development of polymerase chain reaction-based testing, no single clinical diagnostic test has emerged with sufficient sensitivity, specificity, and turnaround time to be entirely reliable for disease diagnosis. The importance of C difficile acquired outside the hospital environment remains an unknown factor and awaits further epidemiologic investigation. This article discusses the changing epidemiology, clinical presentation, and pathogenesis of C difficile infection and highlights the ongoing challenges of laboratory diagnosis, treatment, and disease relapse.
Topics: Animals; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Prognosis; Recurrence
PubMed: 20513554
DOI: 10.1016/j.cll.2010.04.001 -
Journal of Bacteriology Aug 2018Germination of spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, cannot cause disease pathologies unless its spores... (Review)
Review
Germination of spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, cannot cause disease pathologies unless its spores germinate into metabolically active, toxin-producing cells. Recent advances in our understanding of spore germination mechanisms indicate that this process is both complex and unique. This review defines unique aspects of the germination pathways of and compares them to those of two other well-studied organisms, and germination is unique, as does not contain any orthologs of the traditional GerA-type germinant receptor complexes and is the only known sporeformer to require bile salts in order to germinate. While recent advances describing germination mechanisms have been made on several fronts, major gaps in our understanding of germination signaling remain. This review provides an updated, in-depth summary of advances in understanding of germination and potential avenues for the development of therapeutics, and discusses the major discrepancies between current models of germination and areas of ongoing investigation.
Topics: Bacillus anthracis; Bacterial Proteins; Clostridioides difficile; Clostridium Infections; Clostridium perfringens; Humans; Membrane Proteins; Spores, Bacterial
PubMed: 29760211
DOI: 10.1128/JB.00218-18 -
Emerging Microbes & Infections Feb 2018Clostridium difficile is a leading cause of antibiotic-associated diarrhea worldwide. The diagnosis of C. difficile infection (CDI) requires both clinical manifestations... (Review)
Review
Clostridium difficile is a leading cause of antibiotic-associated diarrhea worldwide. The diagnosis of C. difficile infection (CDI) requires both clinical manifestations and a positive laboratory test for C. difficile and/or its toxins. While antibiotic therapy is the treatment of choice for CDI, there are relatively few classes of effective antibiotics currently available. Therefore, the development of novel antibiotics and/or alternative treatment strategies for CDI has received a great deal of attention in recent years. A number of emerging agents such as cadazolid, surotomycin, ridinilazole, and bezlotoxumab have demonstrated activity against C. difficile; some of these have been approved for limited clinical use and some are in clinical trials. In addition, other approaches such as early and accurate diagnosis of CDI as well as disease prevention are important for clinical management. While the toxigenic culture and the cell cytotoxicity neutralization assay are still recognized as the gold standard for the diagnosis of CDI, new diagnostic approaches such as nucleic acid amplification methods have become available. In this review, we will discuss both current and emerging diagnostic and therapeutic modalities for CDI.
Topics: Animals; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Diarrhea; Humans
PubMed: 29434201
DOI: 10.1038/s41426-017-0019-4 -
Advances in Experimental Medicine and... 2016Zoonoses are infections or diseases that can be transmitted between animals and humans through direct contact, close proximity or the environment. Clostridium difficile... (Review)
Review
Zoonoses are infections or diseases that can be transmitted between animals and humans through direct contact, close proximity or the environment. Clostridium difficile is ubiquitous in the environment, and the bacterium is able to colonise the intestinal tract of both animals and humans. Since domestic and food animals frequently test positive for toxigenic C. difficile, even without showing any signs of disease, it seems plausible that C. difficile could be zoonotic. Therefore, animals could play an essential role as carriers of the bacterium. In addition, the presence of the spores in different meats, fish, fruits and vegetables suggests a risk of foodborne transmission. This review summarises the current available data on C. difficile in animals and foods, from when the bacterium was first described up to the present.
Topics: Animals; Clostridioides difficile; Enterocolitis, Pseudomembranous; Food Contamination; Food Microbiology; Humans; Meat; Zoonoses
PubMed: 27350639
DOI: 10.1007/5584_2016_27 -
Journal of Clinical Microbiology Jan 2016Toxinotyping is a PCR-restriction fragment length polymorphism (RFLP)-based method for differentiation of Clostridium difficile strains according to the changes in the... (Review)
Review
Toxinotyping is a PCR-restriction fragment length polymorphism (RFLP)-based method for differentiation of Clostridium difficile strains according to the changes in the pathogenicity locus (PaLoc), a region coding for toxins A and B. Toxinotypes are a heterogenous group of strains that are important in the development of molecular diagnostic tests and vaccines and are a good basis for C. difficile phylogenetic studies. Here we describe an overview of the 34 currently known toxinotypes (I to XXXIV) and some changes in nomenclature.
Topics: Bacterial Proteins; Bacterial Toxins; Clostridioides difficile; Enterotoxins; Genetic Variation; Genotype; Humans; Molecular Typing
PubMed: 26511734
DOI: 10.1128/JCM.02083-15 -
Annals of Laboratory Medicine May 2018Clostridium difficile is a major causative agent of antibiotic-associated diarrhea and has become the most common pathogen of healthcare-associated infection worldwide.... (Review)
Review
Clostridium difficile is a major causative agent of antibiotic-associated diarrhea and has become the most common pathogen of healthcare-associated infection worldwide. The pathogenesis of C. difficile infection (CDI) is mediated by many factors such as colonization involving attachment to host intestinal epithelial cells, sporulation, germination, and toxin production. Bacterial cell surface components are crucial for the interaction between the bacterium and host cells. C. difficile has two distinct surface layer proteins (SLPs): a conserved high-molecular-weight SLP and a highly variable low-molecular-weight SLP. Recent studies have shown that C. difficile SLPs play roles not only in growth and survival, but also in adhesion to host epithelial cells and induction of cytokine production. Sequence typing of the variable region of the slpA gene, which encodes SLPs, is one of the methods currently used for typing C. difficile. SLPs have received much attention in recent years as vaccine candidates and new therapeutic agents in the treatment of C. difficile-associated diseases. Gaining mechanistic insights into the molecular functions of C. difficile SLPs will help advance our understanding of CDI pathogenesis and the development of vaccines and new therapeutic approaches. In this review, we summarize the characteristics and immunological roles of SLPs in C. difficile.
Topics: Bacterial Proteins; Bacterial Vaccines; Clostridioides difficile; Clostridium Infections; Humans; Immunity, Innate
PubMed: 29401552
DOI: 10.3343/alm.2018.38.3.189