Title: Clostridium Difficile Infection Following Chemotherapy. VOLUME: 5 ISSUE: 1. Author(s):Shahzad Raza, Mahadi A. Baig, Helena Russell, Yanick Gourdet and Barbara J. Berger. Affiliation:Department of Medicine Brookdale University Hospital and Medical Center, New York, USA.. Keywords:Chemotherapy, glutamate dehydrogenase test, real-time polymerase chain reaction, enzyme immunoassays, Clostridium difficile infection. Abstract: Clostridium difficile infection (CDI) is a major concern for health care system and clinicians. Interest in C. difficile infection has increased recently due to an ongoing C. difficile epidemic with a hypervirulent strain and mortality. Disease due to C. difficile is responsible for substantial strain on the hospital system by increasing patients length of stay and increasing costs. Present studies have demonstrated chemotherapeutic agents as an independent risk factor for CDI potentially leading towards serious morbidity and mortality. However, the current strategies ...
Clostridium difficile toxin A (TcdA) is a toxin generated by Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridium difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis. TcdA is one of the largest bacterial toxins known. With a molecular mass of 308 kDa, it is usually described as a potent enterotoxin, but it also has some activity as a cytotoxin. The toxin acts by modifying host cell GTPase proteins by glucosylation, leading to changes in cellular activities. Risk factors for C. difficile infection include antibiotic treatment, which can disrupt normal intestinal microbiota and lead to colonization of C. difficile bacteria. The gene contains an open reading frame (ORF) of 8,133 nucleotides, coding for 2,710 amino acids. TcdA and TcdB share 63% homology in their amino acid ...
Clostridium difficile infection (CDI) is a symptomatic infection due to the spore-forming bacterium, Clostridium difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis. Clostridium difficile infection is spread by bacterial spores found within feces. Surfaces may become contaminated with the spores with further spread occurring via the hands of healthcare workers. Risk factors for infection include antibiotic or proton pump inhibitors use, hospitalization, other health problems, and older age. Diagnosis is by stool culture or testing for the bacterias DNA or toxins. If a person tests positive but has no symptoms it is known as C. difficile colonization rather than an infection. Prevention is by limiting antibiotic use; and by hand washing, and terminal room cleaning in hospital. Discontinuation of ...
From webmed.com Clostridium difficile Colitis - Overview What is Clostridium difficile colitis? Clostridium difficile (also called C. difficile) are bacteria that can cause swelling and irritation of the large intestine, or colon . This inflammation, known as colitis, can cause diarrhea, fever, and abdominal cramps. You may get C. difficile colitis if you take antibiotics. C. difficile also can be passed from person to person. The infection is most common in people who are taking antibiotics while in the hospital. It is especially common in older people in hospitals and nursing ho ...
Glutamate dehydrogenase (GDH), an enzyme present in high copy numbers in many organisms, has proved to be a sensitive screening marker for Clostridium difficile. Since GDH is present in many intestinal bacteria, it is crucial that assay systems for glutamate dehydrogenase be accurate and highly sensitive for the detection of C. difficile-specific GDH. The RIDA®QUICK Clostridium difficile GDH immunochromatographic rapid test meets both of these requirements to a high degree. Although it does not eliminate the need for the detection of C. difficile toxins A and B, which is obligatory for the diagnosis of Clostridium difficile infection, the RIDA®QUICK Clostridium difficile GDH difficile rapid test improves the reliability of detection of this very consequential nosocomial pathogen when performed sequentially, i.e., before or parallel to the RIDA®QUICK Clostridium difficile Toxin A/B rapid test. Both the specific clinical symptoms and signs and the positive detection of C. difficile toxins A and ...
New advances in the treatment of Clostridium difficile infection (CDI) Dennis D Hedge, Joe D Strain, Jodi R Heins, Debra K FarverSouth Dakota State University College of Pharmacy, Brookings, SD 57007, USAAbstract: Clostridium difficile infections (CDI) have increased in frequency throughout the world. In addition to an increase in frequency, recent CDI epidemics have been linked to a hypervirulent C. difficile strain resulting in greater severity of disease. Although most mild to moderate cases of CDI continue to respond to metronidazole or vancomycin, refractory and recurrent cases of CDI may require alternative therapies. This review provides a brief overview of CDI and summarizes studies involving alternative antibiotics, toxin binders, probiotics, and immunological therapies that can be considered for treatment of acute and recurrent CDI in severe and refractory situations.Keywords: Clostridium difficile, antibiotics, probiotics, immunological therapy
Background. Previous studies have examined the association between proton pump inhibitor (PPI) use and the risk of Clostridium difficile-associated disease (CDAD), with conflicting results. Whether outpatient PPI use influences the risk of hospital admission for CDAD among older patients who have recently been treated with antibiotics is unknown.. Methods. We conducted a population-based, nested case-control study of linked health care databases in Ontario, Canada, from 1 April 2002 through 31 March 2005. We identified patients aged ⩾66 years who were hospitalized for CDAD within 60 days of receiving outpatient antibiotic therapy. Each case patient with CDAD was matched with 10 control subjects on the basis of age, sex, and details of antibiotic use (antibiotic class, timing, and number of antibiotics used). PPI use by case patients and control subjects was categorized as current (within 90 days), recent (91-180 days), or remote (181-365 days). We used conditional logistic regression to ...
What is C. difficile?. Clostridium difficile is a bacteria that can cause diarrhea, abdominal pain, fever, bowel inflammation (colitis), and rarely severe colitis ("pseudomembranous colitis") and bowel perforation. In its spore (inert) form, it survives heat and frost in the environment; C. difficile spores usually pass through our guts without harm. However, certain triggers, such as antibiotics or proton pump inhibitors, cause C. difficile to grow and produce toxins. These toxins cause the symptoms of diarrhea. How is C. difficile spread?. C. difficile spores are spread on hands of sick patients and healthcare workers, and from surfaces and rooms that are not properly cleaned. Spores are not killed with typical disinfectants; so you need to use a fresh bleach solution (1:10 dilution) or special disinfectants. (EPA List K).. What is "healthcare-associated" C. difficile infection?. In an effort to address the causes of C. difficile infection (CDI), infections have been attributed to ...
Clostridium difficile infections cause morbidity and mortality. The authors conducted a retrospective review of Clostridium difficile infection (CDI) in kidney transplant recipients at their center over a 3 year period. The overall rate of CDI was 6.1% and increased over time during the study. A case-control study was subsequently performed to determine the risk factors for infection. Independent predictors of CDI among kidney transplant recipients were VRE colonization, having a CDC-criteria high risk donor, and administration of high-risk antibiotics such as antipseudomonal penicillins and carbapenems. There were no deaths in this series although 10.8% had recurrent infection. The study highlights the need for judicious antibiotic use and good infection control practices in transplant units.. ...
Clostridium difficile infections (CDI) are the most frequent cause of diarrhoea in hospitals. Geriatric patients are more often affected by the condition, by a relapse and complications. Therefore, a crucial question is how often colonization with toxigenic Clostridium difficile strains occurs in elderly patients without diarrhoea and whether there is a
Feeling CLOSTRIDIUM DIFFICILE COLITIS while using Metronidazole? CLOSTRIDIUM DIFFICILE COLITIS Causes, Patient Concerns and Latest Treatments and Metronidazole Reports and Side Effects.
Results:. An outbreak of C. difficile-associated diarrhea was caused by a clonal isolate of clindamycin-resistant C. difficile and was associated with increased use of clindamycin. Hospital-wide requirement of approval by an infectious disease consultant of clindamycin use led to an overall reduction in clindamycin use, a sustained reduction in the mean number of cases of C. difficile-associated diarrhea (11.5 cases/month compared with 3.33 cases/month; P , 0.001), and an increase in clindamycin susceptibility among C. difficile isolates (9% compared with 61%; P , 0.001). A parallel increase was noted in the use of and costs associated with other antibiotics with antianaerobic activity, including cefotetan, ticarcillin-clavulanate, and imipenem-cilastin. The hospital realized overall cost savings as a result of the decreased incidence of C. difficile-associated diarrhea. ...
Bacteria within biofilms are protected from multiple stresses, including immune responses and antimicrobial agents. The biofilm-forming ability of bacterial pathogens has been associated with increased antibiotic resistance and chronic recurrent infections. Although biofilms have been well studied for several gut pathogens, little is known about biofilm formation by anaerobic gut species. The obligate anaerobe Clostridium difficile causes C. difficile infection (CDI), a major health care-associated problem primarily due to the high incidence of recurring infections. C. difficile colonizes the gut when the normal intestinal microflora is disrupted by antimicrobial agents; however, the factors or processes involved in gut colonization during infection remain unclear. We demonstrate that clinical C. difficile strains, i.e., strain 630 and the hypervirulent strain R20291, form structured biofilms in vitro, with R20291 accumulating substantially more biofilm. Microscopic and biochemical analyses show ...
Author summary The anaerobic, spore-forming bacterium Clostridium difficile (C. difficile) is a prominent pathogen in hospitals worldwide and the leading cause of nosocomial diarrhea. Numerous risk factors are associated with C. difficile infections (CDIs) including: antibiotics, advanced age, vitamin D deficiency, and proton pump inhibitors. Antibiotic use disrupts the intestinal microbiota allowing for C. difficile to colonize, however, why these other risk factors increase CDI incidence is unclear. Notably, deficient intestinal calcium absorption (i.e., increased calcium levels) is associated with these risk factors. In this work, we investigate the role of calcium in C. difficile spore germination. C. difficile spores are the infectious particles and they must become metabolically active (germinate) to cause disease. Here, we show that calcium is required for C. difficile germination, specifically activating the key step of cortex hydrolysis, and that this calcium can be derived from either within
A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen.
TY - JOUR. T1 - Epidemiology and outcomes of clostridium difficile infections in hematopoietic stem cell transplant recipients. AU - Alonso, Carolyn D.. AU - Treadway, Suzanne B.. AU - Hanna, David B.. AU - Huff, Carol Ann. AU - Neofytos, Dionissios. AU - Carroll, Karen C.. AU - Marr, Kieren A.. PY - 2012/4/15. Y1 - 2012/4/15. N2 - Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population.Methods.We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n=999). The median time to diagnosis of CDI was short among both ...
Background Clostridium difficile is a Gram-positive bacteria found in the large bowel or colon that causes mild to severe intestinal conditions and sometimes death. The primary risk factors for development of Clostridium difficile infection (CDI) include healthcare exposure and recent antimicrobial use. The purpose of this study is to compare risk factors associated with CDI occurring in the Community to those associated with Healthcare Facility Associated CDI in the metro Atlanta population from September 1, 2009 - April 30, 2011. Methods Patients were identified through C. difficile surveillance program of the Georgia Emerging Infections Program (EIP). Prospective, population based, laboratory based surveillance for all positive C. difficile cases in the Georgia Health District 3 (HD3). Due to the sampling scheme, for this analysis CO-HCFA and HCFO cases were combined to make a Healthcare Facility Associated (HCFA) classification. Using SAS, a logistic regression analysis was performed to compare the
Evidence-based recommendations on faecal microbiota (bacteria) transplant for recurrent Clostridium difficile (C. difficile/C. diff) infection
Evidence-based recommendations on faecal microbiota (bacteria) transplant for recurrent Clostridium difficile (C. difficile/C. diff) infection
New life-saving treatments for Vaccines Clostridium Difficile-associated Diarrhea in clinical trial on Clostridium difficle Vaccine (C. diff)
Learn more about the Clostridium Difficile-Associated Diarrhea Treatment with Fidaxomicin - Phase IIa clinical study at Childrens Hospital.
RAJABALLY, N et al. The Clostridium difficile problem: A South African tertiary institutions prospective perspective. SAMJ, S. Afr. med. j. [online]. 2013, vol.103, n.3, pp.168-172. ISSN 2078-5135.. BACKGROUND AND OBJECTIVES: The aim of this study is to report the incidence of Clostridium difficile-associated disease (CDAD) in a tertiary-care hospital in South Africa and to identify risk factors, assess patient outcomes and determine the impact of the hypervirulent strain of the organism referred to as North American pulsed-field type 1 (NAP1). METHODS: Adults who presented with diarrhoea over a period of 15 months were prospectively evaluated for CDAD using stool toxin enzyme immunoassay (EIA). Positive specimens were evaluated by PCR. Patient demographics, laboratory parameters and outcomes were analysed. RESULTS: CDAD was diagnosed in 59 (9.2%) of 643 patients (median age 39 years, IQR 30 - 55). Thirty-four (58%) were female. Recent antibiotic exposure was reported in 39 (66%), 27 (46%) had ...
1. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-34. doi: 10.1056/NEJMoa1408913 25714160. 2. Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA internal medicine. 2013;173(14):1359-67. doi: 10.1001/jamainternmed.2013.7056 23780507. 3. Eyre DW, Cule ML, Wilson DJ, Griffiths D, Vaughan A, OConnor L, et al. Diverse sources of C. difficile infection identified on whole-genome sequencing. The New England journal of medicine. 2013;369(13):1195-205. doi: 10.1056/NEJMoa1216064 24066741. 4. Freeman J, Bauer MP, Baines SD, Corver J, Fawley WN, Goorhuis B, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev. 2010;23(3):529-49. doi: 10.1128/CMR.00082-09 20610822. 5. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, et al. ...
Morbidity, Mortality, and Healthcare Burden of Nosocomial Clostridium Difficile-Associated Diarrhea in Canadian Hospitals - Volume 23 Issue 3 - Mark A. Miller, Meagan Hyland, Marianna Ofner-Agostini, Marie Gourdeau, Magued Ishak, Canadian Hospital Epidemiology Committee, Canadian Nosocomial Infection Surveillance Program
[115 Pages Report] Check for Discount on United States Drugs for Clostridium Difficile Infections Market Report 2017 report by QYResearch Group. In this report, the United States Drugs for Clostridium Difficile...
Clostridium difficile is an important nosocomial pathogen, resulting in antibiotic-associated disease ranging from mild diarrhoea to the life-threatening pseudomembranous colitis. Upon antibiotic exposure, it is believed that the normal bowel microflora of patients is disrupted, allowing C. difficile to proliferate. Significantly, C. difficile is among only a few bacteria able to ferment tyrosine to p-cresol, a phenolic compound that is toxic to other microbes via its ability to interfere with metabolism. Therefore, the ability of different C. difficile strains to produce and tolerate p-cresol may play an important role in the development and severity of C. difficile-associated disease. In this study, it was demonstrated that two C. difficile hypervirulent 027 strains (Stoke Mandeville and BI-16) are more tolerant to p-cresol than other C. difficile strains including 630, CF4 and CD196. Surprising, it was shown that Clostridium sordellii also has a high tolerance to p-cresol, suggesting an overlap in
Although mostly associated with antibiotic use in hospitalized patients, C. difficile infections in people in the community have become more common. As of 2014, they accounted for 41 percent of all C. difficile infections, according to the Centers for Disease Control and Prevention (CDC). In this new case-control study, researchers enrolled adult patients from 10 U.S. sites during 2014-2015 who tested positive for C. difficile as an outpatient, or within three days of being hospitalized, and who had not been admitted to a health care facility within the past 12 weeks.. Each patient was matched to a person who did not have a C. difficile infection as a control. All of the study participants-452 total-were interviewed individually by phone to collect information about their health, medication use, recent health care visits, household exposures, and diet. In line with previous studies, larger percentages of patients with community-associated C. difficile infections had prior outpatient health care ...
In order to determine if gas-liquid chromatography (GLC) on concentrated stool extracts could be substituted to cell culture assay for cytotoxicity, we prospectively studied 154 diarrhoeal stools submitted for detection of Clostridium difficile toxin. Isocaproic-positive samples were cultured on egg yolk agar supplemented with cycloserine, cefoxitin and fructose for isolation of C difficile, and on egg yolk agar plus kanamycin for isolation of other clostridium species. Of the 154 samples, 129 were GLC-negative (height of the isocaproic peak less than 1.2 cm) and were toxin-negative. Twenty-five stools yielded isocaproic acid; C difficile isolated from 13 of them, six of which were also toxin-positive. Four other isocaproic-positive samples yielded C bifermentans and C sordellii; all were toxin-negative. These results indicate that a negative GLC is an excellent screening test for excluding C difficile infection; positive results must be checked by toxin testing and culture since they are not ...
Clostridium difficile, the most common cause of hospital-associated diarrhoea in developed countries, presents major public health challenges. The high clinical and economic burden from C. difficile infection (CDI) relates to the high frequency of recurrent infections caused by either the same or different strains of C. difficile. An interval of 8 weeks after index infection is commonly used to classify recurrent CDI episodes. We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. The performance of different intervals between initial and subsequent episodes of CDI was investigated. Of 4612 patients with CDI, 1471 (32%) were identified with recurrence. PCR ribotyping data were available for initial and recurrent episodes for 551 patients. Relapse (recurrence with same ribotype (RT) as index episode) was found in 350 (64%) patients and reinfection (recurrence with new RT) in 201 (36%) patients. Our analysis indicates ...
High-risk patients must be warned about proton pump inhibitors and Clostridium difficile infection, as community-acquired C. difficile infections increase.
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Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60
Clostridium difficile has become the leading cause of nosocomial diarrhea in adults. A substantial increase has occurred in morbidity and mortality associated with disease caused by C difficile and in the identification of new hypervirulent strains, warranting a high clinical index of suspicion for infections due to this organism. Prevention of infection requires a multidisciplinary approach, including early recognition of disease, effective contact isolation precautions, adherence to disinfectant policies, and judicious use of antibiotics. Current treatment approaches are based on the severity of illness. As hypervirulent strains evolve, unsuccessful treatments are more common. Complicated colitis caused by C difficile may benefit from surgical intervention. Subtotal colectomy and end ileostomy have been the procedures of choice, but are associated with a high mortality rate because of late surgical consultation and use of surgery as a salvage therapy. A promising surgical alternative is ...
There are two prerequisites for developing C difficile associated diarrhoea: disruption of the normal gastrointestinal flora, causing diminished colonisation resistance favouring C difficile, and acquisition of the organism from an exogenous source. Other factors include host susceptibility, virulence of the C difficile strain concerned, and the nature and extent of antimicrobial exposure.3. In normal people there are more than 500 species of bacteria in the colon. A gram of faeces normally contains up to 1012 bacteria that resist colonisation and impair multiplication of C difficile. Lactobacilli and group D enterococci display most antagonistic activity,8 and eradication or reduction of such bacteria by antibiotics creates an environmental vacuum for C difficile to fill. People have significant variations in their intestinal microflora and the elderly population are most at risk of C difficile diarrhoea, possibly because their protective bacteroides diversity is more likely to be affected by ...
The data suggests that there were at least four routes of entry for this epidemic strain into UK, three of which arrived independently from North America in Exeter, Ayrshire and Birmingham, and another one which arrived in Maidstone from continental Europe. Dr Fabio Miyajima, from the Universitys Institute of Translational Medicine, said: "We know these organisms are resistant to commonly prescribed antibiotics and disinfectants, including alcohol gel, but perhaps more intriguing is the fact that its rapid spread throughout the world has been more about the ease and frequency with which we travel today". Clostridium difficile is air borne and can be transmitted from infected patients to others. Since it survives in the environment for weeks, there is also a strong possibility that healthy individuals who shared a contaminated ambient could transport the spores through clothing, or even on their hands and hair. "It is important for us to know the ways in which the bacteria can enter various ...
BACKGROUND/OBJECTIVES: It is unclear how medication exposures differ in their association with recurrent Clostridium difficile infection (rCDI) in elderly nursing home (NH) residents and community-dwelling individuals. This study examined these exposures to determine whether the risk of rCDI differs according to living environment. DESIGN: Retrospective. SETTING: Academic and community healthcare settings. PARTICIPANTS: Individuals aged 65 and older with CDI (N = 616). MEASUREMENTS: Information on participant characteristics and medications was extracted from the electronic medical record (EMR). We used separate extended Cox models according to living environment to identify the association between medication use and risk of rCDI. RESULTS: Of the 616 elderly adults treated for CDI, 24.1% of those living in the community and 28.1% of NH residents experienced recurrence within 1 year. For community-dwelling participants, the risk of rCDI was 1.6 times as high with antibiotic exposure and 2.5 times as high
Clostridium difficile, a highly infectious bacterium, is the leading cause of antibiotic-associated pseudomembranous colitis. In 2009, the number of death certificates mentioning C. difficile infection in the U.K. was estimated at 3933 with 44% of certificates recording infection as the underlying cause of death. A number of virulence factors facilitate its pathogenicity, among which are two potent exotoxins; Toxins A and B. Both are large monoglucosyltransferases that catalyse the glucosylation, and hence inactivation, of Rho-GTPases (small regulatory proteins of the eukaryote actin cell cytoskeleton), leading to disorganization of the cytoskeleton and cell death. The roles of Toxins A and B in the context of C. difficile infection is unknown. In addition to these exotoxins, some strains of C. difficile produce an unrelated ADP-ribosylating binary toxin. This toxin consists of two independently produced components: an enzymatic component (CDTa) and the other, the transport component (CDTb) ...
This book outlines the currently available clinical, epidemiological and experimental data on Clostridium difficile infection (CDI) with special emphasis on studies and results achieved in Europe. Th
We determined estimated incidence of and risk factors for community-associated Clostridium difficile infection (CA-CDI) among patients treated at 6 North Carolina hospitals. CA-CDI case-patients were defined as adults (>18 years of age) with a positive stool test result for C. difficile toxin and no hospitalization within the prior 8 weeks. CA-CDI incidence was 21 and 46 per 100,000 person-years in Veterans Affairs (VA) outpatients and Durham County populations, respectively. VA case-patients were more likely than controls to have received antimicrobial drugs (adjusted odds ratio [aOR] 17.8, 95% confidence interval [CI] 6.6-48] and to have had a recent outpatient visit (aOR 5.1, 95% CI 1.5-17.9). County case-patients were more likely than controls to have received antimicrobial drugs (aOR 9.1, 95% CI 2.9-28.9), to have gastroesophageal reflux disease (aOR 11.2, 95% CI 1.9-64.2), and to have cardiac failure (aOR 3.8, 95% CI 1.1-13.7). Risk factors for CA-CDI overlap with those for healthcare
A novel approach to prevent C. difficile infection is to use compounds with activity against C. difficile as primary prophylaxis in high risk patients. Chemoprophylaxis theoretically can prevent C. difficile infection by two mechanisms. It may reduce transmission from asymptomatic C. difficile carriers by reducing the number of spores shed in the stool and prevent replication and subsequent toxin production of the organisms in patients at risk for C. difficile infection ...
Clostridium difficile is the leading infectious cause of nosocomial diarrhea in developed countries. Hospital outbreaks of Clostridium difficile-associated diarrhea (CDAD) are associated with substantial patient morbidity and mortality. Conventional therapy with antibiotics often results in secondary infection with resistant organisms or clinical relapse after discontinuation of the antimicrobial course. New strategies are needed to limit the impact of this opportunistic pathogen. Considerable evidence exists that immunity against C. difficile toxins may be effective in controlling CDAD. 48 subjects will be enrolled to receive one of three dose levels of modified C difficile vaccine or placebo administered on a 3-dose schedule. The study consists of a 30-day screening period, a 70-day treatment period, one follow-up phone interview 2 months after the last vaccination, and one follow-up clinic visit 6 months after the last vaccination ...
Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for TcdA and TcdB mediated cellular responses are complex, it has been shown that these toxins can alter chemotactic responses of neutrophils and intestinal epithelial cells leading to innate immune responses and tissue damages. The effects of C. difficile toxins on the migration and trafficking of other leukocyte subsets, such as T lymphocytes, are not clear and may have potential implications for adaptive immunity. We investigated here the direct and indirect effects of TcdA and TcdB on the migration of human blood T cells using conventional cell migration assays and microfluidic devices. It has been found that, although both toxins decrease T cell motility, only TcdA but not TcdB decreases T cell chemotaxis. Similar
Clostridium difficile is an important cause of antibiotic-associated diarrhoea. The simultaneous presence of different strains in individual faecal samples has not yet been established, but is important for epidemiological studies. Recurrences of Clostridium difficile-associated diarrhoea (CDAD) are observed in 15-20 % of patients and have been reported as relapses or reinfections with a new strain. In a period of 1 year, 28 faecal samples from 23 patients with a first episode of CDAD were collected at the Leiden University Medical Centre. In addition, 52 faecal samples from 23 patients, from three different hospitals, with one (n = 19), two (n = 2) or three (n = 2) recurrences were studied. PCR-ribotyping was applied as the standard typing method for the isolates. The toxinogenic and clindamycin-resistance profiles of the isolates was determined by PCR. Of 23 patients with a first episode of CDAD, two (8.7 %) harboured two different types, with no differences in toxinogenicity or clindamycin resistance
Optimer announced the combined data from its two Phase 3 trials of fidaxomicin for the treatment of patients with Clostridium difficile infection (CDI).
Some Clostridium difficile strains produce, in addition to toxins A and B, the binary toxin Clostridium difficile transferase (CDT), which ADP-ribosylates actin and may contribute to the hypervirulence of these strains. The separate binding and translocation component CDTb mediates transport of the enzyme component CDTa into mammalian target cells. CDTb binds to its receptor on the cell surface, CDTa assembles and CDTb/CDTa complexes are internalised. In acidic endosomes, CDTb mediates the delivery of CDTa into the cytosol, most likely by forming a translocation pore in endosomal membranes. We demonstrate that a seven-fold symmetrical positively charged β-cyclodextrin derivative, per-6-S-(3-aminomethyl)benzylthio-β-cyclodextrin, which was developed earlier as a potent inhibitor of the translocation pores of related binary toxins of Bacillus anthracis, Clostridium botulinum and Clostridium perfringens, protects cells from intoxication with CDT. The pore blocker did not interfere with the CDTa
Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacterium that causes infections in the gastrointestinal tract. The mechanisms by which C. difficile is able to germinate in such a toxic environment are not fully understood. However, our lab and others have shown that certain bile components have the capacity to induce C. difficile spore germination and affect growth of C. difficile cells. Interestingly, C. difficile encodes a bile salt hydrolase (cholylglycine hydrolase), but it is unknown how this affects the bacteriums ability to grow in the presence of bile acids. This research project is centered around the goal of inserting a mutation into the C. difficile bile salt hydrolase. This will be completed using the TargeTron Gene Knockout System, which inserts group II introns into a specific DNA location, and allelic-coupled exchange. Successful completion of this project would allow further investigation into the relationship between C. difficiles bile salt hydrolase ...
title: Epidemiology and clinical features of toxigenic culture-confirmed hospital?onset Clostridium difficile infection: A multicentre prospective study in tertiary hospitals of South Korea, doi: 10.1099/jmm.0.070672-0, category: Article
C. difficile ribotype 027 (RT027) is the epidemic strain found primarily in North America. Studies have suggested an enhanced virulence phenotype for RT027 such as increased toxin production, but the impact on disease severity on in vivo models is not well understood. This study describes the in vitro characterization of important virulence characteristics for several RT027 and non-RT027 C. difficile clinical isolates, and how these factors may impact disease severity in the hamster and mouse C. difficile associated disease models. Six RT027 and six non-RT027 clinical isolates were evaluated in vitro for total spore counts and Toxin A/B titers in 72H broth cultures. Spore counts were generated from heat/ethanol shock culture samples and plated onto CCFA containing 0.1% taurocholate, and toxin A/B titers were determined from spent broth with the tgcBIOMICS ELISA assay. The mouse C. difficile model involved being administered for 5 days through oral gavage or drinking water. The mice were then placed on a
The research team analyzed hospital admissions from 1998 to 2004 for demographics, length of stay, C difficile infections. The research team also analyzed time from admission to a positive C difficile test.. The team calculated C difficile-associated disease incidence for non-IBD, IBD, Crohns-disease, and ulcerative colitis admissions.. The researchers used logistic regression to estimate the risk for C difficile-associated disease.. The team found C difficile-associated disease incidence increased in each group.. The incidence of C difficile was higher in all groups with IBD than non-IBD groups.. During the observation period, C difficile-associated disease rates approximately doubled in Crohn-disease, and tripled in ulcerative colitis.. The researchers observed that length of stay was similar among the groups.. For all years combined, the adjusted odds ratio for C difficile-associated disease in all IBD admissions was 3.. The team noted that the adjusted odds ratio for C difficile-associated ...
Testing is generally not necessarily for patients with formed stools (no diarrhea). The gold standard for diagnosis of C. difficile infection is cell culture cytotoxic assay, but it is rarely used clinically (difficult technique and time consuming). Among patients with diarrhea,C. difficile infection is diagnosed either by enzyme immunoassay (ELISA) for toxins A and/or B in stools or by DNA-based tests (PCR) that detect bacterial toxin genes in stools. Although both ELISA and DNA-based tests may be performed sequentially, only one positive test is sufficient to diagnose C. difficile infection. Both ELISA and DNA-based tests also have a high negative predictive value , 95% among average-risk patients, and generally negative results warrants the search for alternative diagnoses. The advantage of DNA-based tests over ELISA is that it may detect the presence of BI/NAP1/027 strain, which alters the management plan. However, DNA-based tests may also detect clinically irrelevant findings that may delay ...