... be limited. Home Visit Global Sites Search Help? Clostridium difficile and C. difficile Toxin Testing Share this page: ... C. diff; C diff antigen; GDH Formal name: Clostridium difficile Culture; C. difficile Toxin, A and B; C. ...
Geller, Stephen A.; Fernando Peixoto Ferraz de Campos
Clostridium difficile is the leading cause of hospital-acquired diarrhea in Europe and North America and is a serious re-emerging pathogen. Recent outbreaks have led to increasing morbidity and mortality and have been associated with a new strain (BI/NAP1/027) of C. difficile that produces more toxin than historical strains. With the increasing incidence of C. difficile infection, clinicians have also seen a change in the epidemiology with increased infections in previously low-risk populatio...
Hudson, Darren A; Gibb, A. Patrick; Gill, M John
Extraintestinal infections of Clostridium difficile are rare and often associated with underlying disorders. A case of empyema caused by aspiration of C difficile in a patient with carcinoid syndrome and C difficile colitis is described.
Jensen, M B F; Olsen, K E P; Nielsen, X C;
The diagnosis of Clostridium difficile infection (CDI) requires the detection of toxigenic C. difficile or its toxins and a clinical assessment. We evaluated the performance of four nucleic acid amplification tests (NAATs) detecting toxigenic C. difficile directly from faeces compared to routine...... ribotyping and toxinotyping (TT) were performed on culture-positive samples. In parallel, the samples were analysed by four NAATs; two targeting tcdA or tcdB (illumigene® C. difficile and PCRFast® C. difficile A/B) and two multi-target real-time (RT) PCR assays also targeting cdt and tcdC alleles...... characteristic of epidemic and potentially more virulent PCR ribotypes 027, 066 and 078 (GeneXpert® C. difficile/Epi and an 'in-house RT PCR' two-step algorithm). The multi-target assays were significantly more sensitive compared to routine toxigenic culture (p < 0.05) and significantly more robust to inhibition...
Trudel, Judith L.
Clostridium difficile enterocolitis is endemic in most modern hospitals. The spectrum of clinical presentation varies from the asymptomatic carrier state to fulminant colitis with toxic megacolon and perforation. Highly toxigenic and lethal strains of C. difficile have emerged worldwide. Medical treatment consists of discontinuing the precipitating antibiotic, supportive measures and bowel rest, and antibiotic treatment with metronidazole or vancomycin. Surgical treatment may be necessary in ...
Full Text Available An 80-year-old man was diagnosed to have pneumonia and advanced chronic kidney disease. He presented with anuria and hemodialysis, by temporary femoral catheter, was initiated. He was empirically treated with imipenem/cilastatin 500 mg/24 h after hemodialysis. After 10 days of antibiotic intake, he developed severe diarrhea. Diagnosis of Clostridium difficile (CD-associated diarrhea was confirmed by detection of the toxins A and B in his stool. Imipenem therapy was discontinued; Vancomycin 500 mg orally every 6 h and 1000 mg per rectum every day was added. After two weeks of this treatment, the patient reported complete resolution of the diarrhea and stool samples were negative for Clostridium toxin. In this case, the most possible cause of CD colitis was considered to be imipenem because of the temporal relationship between exposure to the drug and onset of symptoms.
Onderdonk, A B; Cisneros, R L; Bartlett, J. G.
Germfree mice associated with Clostridium difficile developed intestinal disease characterized by polymorphonuclear cell infiltration of the lamina propria, diarrhea, and cecal cytotoxin concentrations positive at a 10(-6) dilution. The numbers of viable bacteria never exceeded 10(10) colony-forming units per g (dry weight). Despite the high toxin levels and chronic inflammation over a 30-day period, the mortality rate was low (less than 2%). Daily treatment of these animals with two oral dos...
Türlü, Ceylan; Coskun, Derya; Amirthananthan, Biveshne
Clostridium difficile er en velkendt årsag til antibiotika- og hospitalsassocieret diarré og pseudomembranøs kolitis. I dag bliver man oftest behandlet for Clostridium difficile infektion med antibiotika, men cirka 20 % af patienter oplever recidiv med Clostridium difficile infektion, uanset valg af antibiotikabehandling. I dette projekt sammenholdes antibiotikabehandling med fækal mikrobiota transplantation for, at undersøge hvilke behandlingsmetoder der er mest effektive til behandling af r...
Smits, Wiep Klaas; Lyras, Dena; Lacy, D Borden; Wilcox, Mark H; Kuijper, Ed J
Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota. PMID:27158839
Public Health Agency
This leaflet provides healthcare patients, their families and carers with comprehensive information on Clostridium difficile (C. diff) infection. It provides some background on the infection�and highlights a range of key factors, including the symptoms to look out for, common causes of contamination, the appropriate course of action should you become infected, and possible treatment options. It also offers advice to visitors and carers on precautions and rules they should follow when in the p...
Public Health Agency
This leaflet provides healthcare patients, their families and carers with comprehensive information on Clostridium difficile (C. diff) infection. It provides some background on the infectionand highlights a range of key factors, including the symptoms to look out for, common causes of contamination, the appropriate course of action should you become infected, and possible treatment options. It also offers advice to visitors and carers on precautions and rules they should follow when in the pr...
Toma, S.; Lesiak, G; Magus, M; Lo, H L; Delmée, M.
A total of 246 live Clostridium difficile cultures were serotyped by a slide agglutination technique. Fifteen grouping antisera were produced which serotyped 98% of the cultures (241 of 246). Our results indicated that certain serogroups may have specific pathogenicity. Strains of serogroups A, G, H, K, S1, and S4 were cytotoxigenic and were isolated mainly from adult patients with pseudomembranous colitis or antibiotic-associated diarrhea. Nontoxigenic strains of serogroups D and Cd-5 were i...
Stephen A. Geller
Full Text Available Clostridium difficile infection (CDI is a significant and increasing medical problem, surpassing methicillin-resistant Staphylococcus aureus as the most common hospital-onset or facility-associated infection, and a key element in the challenging battle against hospital-acquired infections. This Gram-positive, anaerobic, spore-forming colonizes the intestinal tract after antibiotics have altered the normal intestinal flora.
Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 °C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116. PMID:27397423
Kim, Sun Chul; Seo, Min Young; Lee, Jun Yong; Kim, Ki Tae; Cho, Eunjung; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu
Background/Aims: It has been suggested that chronic kidney disease (CKD) is a risk factor for Clostridium difficile infection (CDI) and is associated with increased mortality among patients infected with C. difficile. However, recent studies of the clinical impact of CKD on CDI in Asians are still insufficient. We sought to determine the relationship between CKD and CDI in a Korean population. Methods: This was a single-center, retrospective case-control study. In total, 171 patients with CDI were included as cases and 342 age- and gender-matched patients without CDI were used as controls. We compared the prevalence of CKD in the study sample and identified independent risk factors that could predict the development or prognosis of CDI. Results: Independent risk factors for CDI included stage IV to V CKD not requiring dialysis (odds ratio [OR], 2.90) and end-stage renal disease requiring dialysis (OR, 3.34). Patients with more advanced CKD (estimated glomerular filtration rate < 30) and CDI showed higher in-hospital mortality and poorer responses to the initial metronidazole therapy. Conclusions: More advanced CKD is an independent risk factor for CDI and is associated with higher in-hospital mortality and poor treatment responses in CDI patients. Thus, in CKD patients, careful attention should be paid to the occurrence of CDI and its management to improve the outcome of CDI. PMID:26767866
Roy, Abhik; Lichtiger, Simon
Background Prolonged antibiotic use is limited by several adverse effects, one of which is Clostridium difficile infection (CDI). The aim of this study was to determine the incidence of CDI in patients receiving chronic antibiotic treatment for Crohn’s disease (CD). Methods We conducted a retrospective review of 100 patients with CD for which ≥6 months of outpatient antibiotic therapy was prescribed. Data were collected regarding demographics, CD phenotype, treatment history, and CDI. The incidence of CDI in our patient population was calculated and compared with historical controls. Results 100 patients were studied—60% of men, mean age 23.9 years at CD diagnosis. Eighty-two percent had disease involving the ileum, and 33% had disease involving the colon. The mean duration of antibiotic therapy was 39.6 months (range, 6–217 months). The most commonly prescribed classes of antibiotics were fluoroquinolones (84%), penicillins (57%), and cephalosporins (32%). Forty-nine percent of patients were treated with concomitant thiopurines, 45% with budesonide, and 41% with biologics. The overall incidence of CDI was 2%. This incidence of CDI was lower than previously reported for non-CD patients receiving chronic antibiotics for continuous-flow left ventricular assist device infections (12.5%) and orthopedic prosthesis infections (22.2%). Conclusions The incidence of CDI is rare in patients receiving chronic antibiotic treatment for CD, and it seems significantly lower than for non-CD populations reported in the literature. PMID:26650148
Hull, Mark W.; Beck, Paul L
OBJECTIVE: To review the basic microbiology, pathogenesis of disease, and diagnosis of the nosocomial pathogen Clostridium difficile and to examine therapies recommended by the Canadian Task Force on Preventive Health Care. QUALITY OF EVIDENCE MEDLINE: was searched using MeSH headings. Controlled trials for therapy were sought, but case-control studies and observational reviews were included. MAIN MESSAGE: Clostridium difficile causes approximately 20% of cases of diarrhea associated with ant...
Katherine R Hargreaves; Clokie, Martha R. J.
Phages that infect Clostridium difficile were first isolated for typing purposes in the 1980s, but their use was short lived. However, the rise of C. difficile epidemics over the last decade has triggered a resurgence of interest in using phages to combat this pathogen. Phage therapy is an attractive treatment option for C. difficile infection, however, developing suitable phages is challenging. In this review we summarize the difficulties faced by researchers in this field, and we discuss th...
Phages that infect Clostridium difficile were first isolated for typing purposes in the 1980s, but their use was short lived. However, the rise of C. difficile epidemics over the last decade has triggered a resurgence of interest in using phages to combat this pathogen. Phage therapy is an attractive treatment option for C. difficile infection, however developing suitable phages is challenging. In this review we summarise the difficulties faced by researchers in this field, and we discuss the...
Rampling, A.; Warren, R. E.; Bevan, P C; Hoggarth, C E; Swirsky, D; Hayhoe, F G
Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unu...
Clostridium difficile is a Gram positive pathogen of significant importance in the UK, Europe and the USA. No vaccine has been developed and current treatments are focused on hospital management and the use of antibiotics. The disease is spread in hospitals in the spore form and the role of spores in C. difficile infecton is poorly understood. In this project spores of C. difficile have been characterised. The proteins from the outermost layers of the spore were identified and the genes clone...
Bouillaut, Laurent; McBride, Shonna M; Sorg, Joseph A.
Clostridium difficile is a Gram-positive, spore forming, anaerobic, intestinal bacterium and is the most common cause of antibiotic-associated colitis. For many years this organism was considered genetically intractable, but in the past 10 years, multiple methods have been developed or adapted for genetic manipulation of C. difficile. This unit describes the molecular techniques used for genetic modification of this organism, including methods for gene disruption, complementation, plasmid int...
Clostridium difficile is a is a Gram potential human pathogen. It causing symptoms ranging from mild C. difficile associated diarrhea (CDAD) to severe inflammation of the colon including pseudomembranous colitis and fulminant colitis. Over 300 000 and about 10 000 CDAD episodes are diagnosed annually in the USA and Sweden, respectively. Onset of CDAD is typically associated with antibiotic therapy. These drugs may disrupt the colonization resistance of the colon microflora a...
Allen, Upton D
An increase in Clostridium difficile infection incidence has been observed among hospitalized children in the United States. The present statement, targeted at clinicians caring for infants and children in community and institutional settings, summarizes the relevant information relating to the role of C difficile in childhood diarrhea and provides recommendations for diagnosis, prevention and treatment. Significant differences between adult and paediatric risk factors and disease are discuss...
Gerding, Dale N.; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus
Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylatio...
Lee, Nan-Yao; Huang, Yu-Tsung; Hsueh, Po-Ren; Ko, Wen-Chien
To determine clinical characteristics and outcome of patients with Clostridium difficile bacteremia (CDB), we identified 12 patients with CDB in 2 medical centers in Taiwan; all had underlying systemic diseases. Five had gastrointestinal diseases or conditions, including pseudomembranous colitis (2 patients); 4 recalled diarrhea, but only 5 had recent exposure to antimicrobial drugs. Ten available isolates were susceptible to metronidazole and vancomycin. Five isolates had C. difficile toxin ...
Seekatz, Anna M.; Young, Vincent B.
Clostridium difficile infection (CDI) is the leading health care–associated illness. Both human and animal models have demonstrated the importance of the gut microbiota’s capability of providing colonization resistance against C. difficile. Risk factors for disease development include antibiotic use, which disrupts the gut microbiota, leading to the loss of colonization resistance and subsequent CDI. Identification of the specific microbes capable of restoring this function remains elusive. F...
Wight, N.; Curtis, H.; Hyde, J.; Borriello, S P; Mahida, Y R
At our hospital, the number of cases of Clostridium difficile-associated diarrhoea increased from 29 in 1993 to 210 in 1995. The case notes of 110 patients with C difficile-associated diarrhoea during the first 6 months of 1995 were analysed retrospectively. The majority of the patients (106) had received antibiotics before the onset of diarrhoea; 46 had received three or more different antibiotics and 28 had received metronidazole. In 19 patients, the first stool sample after the onset of di...
Dapa, Tanja; Unnikrishnan, Meera
Clostridium difficile infection (CDI) is a major healthcare-associated disease worldwide. Recurring infections and increasing antibiotic resistance have complicated treatment of CDI. While C. difficile spores are important for transmission and persistence of CDI, other factors such as gut colonization and formation of bacterial communities in the gut may also contribute to pathogenesis and persistence, but have not been well investigated. Recently, we reported that important clinical C. diffi...
Clostridium difficile toxin with production is the most common cause of nosocomial enteric infections. It causes inflammatory bowel disease called Clostridium difficile infection (CDI) of varying severity - from trivial diarrhea to life-threatening conditions such as paralytic ileus and toxic megacolon. C.difficile still escapes the attention of the general public and is in the background of other bacteria, such as MRSA. Clostridium difficile is a strictly anaerobic bacterium. It is a gram-po...
Ehrich, M.; Van Tassell, R L; Libby, J M; Wilkins, T D
We have produced antitoxin to the toxin of Clostridium difficile in rabbits and in goats. Antitoxin dilutions of 1/8,000 and 1/5,120 were capable of neutralizing lethal doses of the toxin in mice and in tissue culture, respectively.
Shuttleworth, R; Taylor, M.; Jones, D M
The antimicrobial susceptibilities of 78 strains of Clostridium difficile isolated from patients with and without gastrointestinal symptoms were determined and compared. Strains from patients with symptoms were more likely to show resistance to antibiotics. The antimicrobial susceptibilities of toxigenic and non-toxigenic strains were found to be similar.
Price, E H; Wright, V. M.; Walker-Smith, J A; Tabaqchali, S
Clostridium difficile belonging to groups not normally detected in infancy was the only potential pathogen detected in the stools of two infants with severe enterocolitis. Further information regarding the virulence of this organism was obtained by use of a recently introduced typing scheme.
Dr. Jon Mark Hirshon, Associate Professor of Emergency Medicine at the University of Maryland School of Medicine, discusses Clostridium difficile infection in outpatients. Created: 11/7/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Date Released: 11/21/2011.
George Zhanel; Greg Hammond
Clostridium difficile is an emerging pathogen that causes C difficile-associated diarrhea, an important nosocomial infection. Control of this infection remains a challenge, and much needs to be determined about the antimicrobial resistance of the organism, antibiotic stewardship, contamination of the patient environment, and various host factors that determine susceptibility or resistance to infection. A national symposium focusing on C difficile infections, the Clostridium difficile Symposiu...
Drucker, D B; Wardle, H. M.; Boote, V.
Phospholipid molecular species present in 32 isolates of Clostridium difficile were examined by fast atom bombardment-mass spectrometry in negative-ion mode. This revealed major anions consistent with the expected presence of the following phosphatidylglycerol (PG) analogs: PG(31:2), PG(32:1), PG(33:2), PG(33:1), PG(34:2), and PG(34:1). The major phospholipid molecular species are distinct from those of other bacterial groups examined.
North America has seen increasing numbers of hospitalised patients and others in nursing homes and the community, with more severe Clostridium difficile associated diarrhoea. This is also described in Northern Europe and surveillance systems are being developed or improved to monitor the situation. One strain (ribotype O27) is described in detail and, like other emerging strains, is demonstrating increasing antimicrobial resistance, notably to quinolone antibiotics. However, its association w...
DePestel, Daryl D.; David M. Aronoff
There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st Century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challeng...
Arrich, Jasmin; Sodeck, Gottfried H.; Sengölge, Gürkan; Konnaris, Christoforos; Müllner, Marcus; Laggner, Anton N; Domanovits, Hans
AIM: Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population. Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea.
Kim, Peter K.; Huh, Heesun C.; Cohen, Hillel W.; Feinberg, Elyssa J.; Ahmad, Salman; Coyle, Christina; Teperman, Sheldon; Boothe, Hugh
Background: Clostridium difficile colitis is associated with increased age, antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to medical therapy may require surgical intervention including subtotal colectomy. We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for inpatients with severe C. difficile colitis and compared the response to this therapy in patients from the community and nursing homes.
Martinelli, Massimo; Strisciuglio, Caterina; Veres, Gabor;
BACKGROUND: Clostridium difficile infection is associated with pediatric inflammatory bowel disease (IBD) in several ways. We sought to investigate C. difficile infection in pediatric patients with IBD in comparison with a group of children with celiac disease and to evaluate IBD disease course of...... period, stool specimens for C. difficile toxins analysis were collected from 112 children with celiac disease as controls. RESULTS: Clostridium difficile occurrence was significantly higher in patients with IBD compared with patients with celiac disease (7.5% versus 0.8%; P = 0.008). Clostridium...... C. difficile infected patients. METHODS: In this prospective, comparative, multicenter study, 211 pediatric patients with IBD were enrolled from October 2010 to October 2011 and tested for the presence of C. difficile toxins A and B in their stools at 0, 6, and 12 months. During the same study...
Clostridium difficile is a common cause of diarrhea in healthcare settings but little is known about what causes cases in the community. In this podcast, CDC's Dr. L. Clifford McDonald discusses two papers in the May 2009 edition of Emerging Infectious Diseases that explore whether the organism could be found in meat samples purchased in grocery stores in Arizona and Canada. Created: 4/16/2009 by Emerging Infectious Diseases. Date Released: 4/16/2009.
Mahony, D E; Bell, P D; Easterbrook, K. B.
Two temperate bacteriophages of differing morphology and host range were isolated by screening 94 isolates of Clostridium difficile. Phage 41 had a 300-nm flexible tail, whereas phage 56 had a shorter tail with a contractile sheath. Electron microscopy of phage 56 lysates exposed to elevated magnesium concentrations showed small virus-like particles which were 21 nm in diameter. The addition of MgCl2 to semisolid agar overlays enhanced both the titer and plaque size of phage 56. Phage 56 was ...
Burgner, D P; Rfidah, H; Beattie, T J; Seal, D V
Six children are described who developed diarrhoea associated with Clostridium difficile during the course of haemolytic uraemic syndrome. The significance of this infection is discussed within the context of the pathophysiology of haemolytic uraemic syndrome.
Michael R. Simon
Full Text Available Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection.
McGlone, S. M.; Bailey, R R; Zimmer, S. M.; Popovich, M. J.; Y. Tian; Ufberg, P.; Muder, R R; Lee, B Y
Although Clostridium difficile (C. difficile) is the leading cause of infectious diarrhoea in hospitalized patients, the economic burden of this major nosocomial pathogen for hospitals, third-party payers and society remains unclear. We developed an economic computer simulation model to determine the costs attributable to healthcare-acquired C. difficile infection (CDI) from the hospital, third-party payer and societal perspectives. Sensitivity analyses explored the effects of varying the cos...
Burke, Kristin E.; Lamont, J. Thomas
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 rec...
Diab, SS; Songer, G; Uzal, FA
Clostridium difficile is considered one of the most important causes of diarrhea and enterocolitis in horses. Foals and adult horses are equally susceptible to the infection. The highly resistant spore of C. difficile is the infectious unit of transmission, which occurs primarily via the fecal-oral route, with sources of infection including equine feces, contaminated soil, animal hospitals, and feces of other animals. Two major risk factors for the development of C. difficile associated disea...
Jin, Ke; Wang, Shixia; Huang, Zuhu; Lu, Shan
Clostridium difficile (C. difficile) infection has become one of the major hospital-associated infections in Western countries in the last two decades. However, there is limited information on the status of C. difficile infection in Chinese healthcare settings. Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China, it is critical to understand the epidemiology and potential risk factors that may contribute ...
Simpson, A J; Das, S. S.; Tabaqchali, S
Pleural infection with Clostridium difficile is extremely rare. A case of nosocomial empyema following chest drain insertion in a 46 year old man is described. The potential of C difficile to cause extra-intestinal infections should be recognised and its isolation from other sites should not be ignored.
Berg, Renate Johanna van den
Clostridium difficile was first discovered in 1935, but it was not until 1977 that this bacterium was found to be associated with pseudomembranous colitis. The disease was considered to be caused by the production of two C. difficile toxins, toxins A and B (TcdA and TcdB). TcdA was shown to exhibit
Bauer, Martijn Philippe
Clostridium difficile is a spore-forming bacterium, the toxin-producing strains of which cause colitis. Risk factors are antibiotics, advanced age and severe comorbidity. C. difficile infection (CDI) has been regarded as mostly a hospital-acquired infection. Preventing relapses is considered the big
The incidence and severity of disease associated with toxigenic Clostridium difficile have increased in hospitals in North America from the emergence of newer, more virulent strains. Toxigenic C. difficile has been isolated from food animals and retail meat with potential implications of transfer t...
Derek M. Tang
Full Text Available Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.
Clostridium difficile on anaerobi sauvabakteeri, joka muodostaa itiöitä. Osa kannoista tuottaa toksiineita. Clostridium difficile -bakteerin tuottamat toksiinit ovat suurin syy antibioottihoitoon liittyvään ripuliin ja pseudomembranoottiseen koliittiin eli paksusuolen tulehdukseen. Clostridium difficile -bakteerin aiheuttamaa tautia kutsutaan Clostridium difficile –infektioksi eli CDI:ksi. Joskus tauti voi johtaa jopa kuolemaan. Infektioita esiintyy antibioottihoidon yhteydessä iäkkäillä tai ...
Czepiel, Jacek; Biesiada, Grażyna; Perucki, William; Mach, Tomasz
Clostridium difficile is a bacterium widely distributed in the human environment. In the last decade the incidence and severity of Clostridium difficile infection has grown, particularly in Europe and North America, making it one of the more common nosocomial infections. A group particularly susceptible to Clostridium difficile infection are patients with inflammatory bowel disease, especially those with involvement of the colon. This paper presents relevant data on Clostridium difficile infe...
Sandell, Staffan; Rashid, Mamun-Ur; Jorup-Rönström, Christina; Ellström, Kristina; Nord, Carl Erik; Weintraub, Andrej
Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0-6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up. PMID:26802875
Tillotson, Glenn S.; Tillotson, Joni
Clostridium difficile has been recognized as a pathogen in humans for over 40 years, but in the past decade the incidence has increased and, more importantly, the clinical presentation and consequences have become more serious, with increased morbidity and mortality. The emergence of a new, more pathogenic strain, BI/NAP1/027, has driven these shifts. Treatment of this disease has been with two antibiotics, metronidazole and vancomycin, but increasing recurrence, not uncommon with C. difficil...
Bauer, Martijn Philippe
Clostridium difficile is a spore-forming bacterium, the toxin-producing strains of which cause colitis. Risk factors are antibiotics, advanced age and severe comorbidity. C. difficile infection (CDI) has been regarded as mostly a hospital-acquired infection. Preventing relapses is considered the biggest challenge in CDI management. In this thesis, we show that CDI occurs in Dutch general practices, often in patients without contact with hospitals. Also, we show that the emerging virulent stra...
Khanna, Sahil; Pardi, Darrell S.
Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emer...
Clostridium difficile is an antibiotic-resistant bacterium that causes diarrhea and sometimes serious intestinal illnesses. In recent years, C. difficile infections have been increasing in number and severity, including among some people outside healthcare settings. In this podcast, CDC's Dr. Michael Jhung discusses his recent study that looked at a new, increasingly prevalent strain of C. difficile in people and compared it to a strain historically found in animals to see whether the two might be linked. The study is published in the July 2008 issue of Emerging Infectious Diseases. Created: 6/30/2008 by Emerging Infectious Diseases. Date Released: 7/3/2008.
D. Spînu; Ovidiu Bratu; Popescu, R.; Marcu, D; A. Rădulescu; Dan Mischianu
Introduction: Clostridium difficile infection stands nowadays as one of the major emerging health problems still underestimated. Only in 2009 the European Society of Clinical Microbiology and Infection (ESCMID) was able to publish guidelines for this serious disease. Actually the guidelines were updated in 2013 so we can speak of a united action towards the resolution of this healthcare problem. Methods: This is a review article aiming to shed light in various aspects of clostridium dif...
Honda, Hitoshi; Dubberke, Erik R.
Clostridium difficile infection is an important healthcare-associated infection. The incidence and severity of C. difficile infection are increasing. Recent C. difficile infection outbreaks with high proportions of severe outcomes have been linked to an emerging, hypervirulent strain of C. difficile. Recently recognized risk factors of C. difficile infection include fluoroquinolone exposure and gastric acid suppression. Effective prevention measures for C. difficile infection include contact ...
Rodriguez-Palacios, Alexander; Staempfli, Henry R.; Duffield, Todd; Weese, J. Scott
Clostridium difficile was isolated from 12 (20%) of 60 retail ground meat samples purchased over a 10-month period in 2005 in Canada. Eleven isolates were toxigenic, and 8 (67%) were classified as toxinotype III. The human health implications of this finding are unclear, but with the virulence of toxinotype III strains further studies are required.
María E Negrón
Full Text Available BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients.
Bauer, Martijn P; Notermans, Daan W; van Benthem, Birgit H B;
Little is known about the extent of Clostridium difficile infection in Europe. Our aim was to obtain a more complete overview of C difficile infection in Europe and build capacity for diagnosis and surveillance.......Little is known about the extent of Clostridium difficile infection in Europe. Our aim was to obtain a more complete overview of C difficile infection in Europe and build capacity for diagnosis and surveillance....
Peacock, Oliver; Speake, William; Shaw, Aidan; Goddard, Andrew
Clostridium difficile infection is associated with antibiotic therapy and usually limited to the colonic mucosa. However, it is also a rare cause of enteritis, with only a few cases reported in the literature. In the present report, the case of a 30-year-old woman with Clostridium difficile enteritis who previously had a panproctocolectomy with end ileostomy for severe ulcerative colitis is described. Previously reported cases of Clostridium difficile enteritis are also reviewed. Previous ant...
Moncrief, J S; Barroso, L A; Wilkins, T D
The toxigenic element of Clostridium difficile VPI 10463 contains a small open reading frame (ORF) immediately upstream of the toxin B gene (G. A. Hammond and J. L. Johnson, Microb. Pathog. 19:203-213, 1995). The deduced amino acid sequence of the ORF, which we have designated txeR, encodes a 22-kDa protein which contains a helix-turn-helix motif with sequence identity to DNA binding regulatory proteins. We used a DNA fragment containing the C. difficile toxin A repeating units (ARU) as a rep...
Hanping Feng; Tor Savidge; Xingmin Sun
The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by act...
Brazier, J S
According to the UK media and popular press, Clostridium difficile is now a fully fledged member of that notorious but ill-defined group of microorganisms portrayed to the general public as superbugs. Following the trail blazed by methicillin-resistant Staphylococcus aureus (MRSA), C. difficile has made the transition from being an obscure anaerobic bacterium, mainly of interest to specialist anaerobic microbiologists, to that of an infamous superbug responsible for outbreaks of hospital-acquired infection that commonly result in serious disease and death. This review tracks the rise in scientific knowledge and public awareness of this organism. PMID:18476496
O'Connor, K A
BACKGROUND: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients. AIM: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients. DESIGN: Retrospective analysis. METHODS: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data. RESULTS: Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03). DISCUSSION: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.
Lessa, Fernanda C.; Gould, Carolyn V; McDonald, L. Clifford
The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare set...
Chilton, Caroline Hazel
The recent increase in availability of next generation sequencing methodologies has led to extensive analysis of the genome of Clostridium difficile. In contrast, protein expression analysis, crucial to the elucidation of mechanisms of disease, has severely lagged behind. In this study, in-depth proteomic analysis of three strains of varying virulence, demonstrated previously in an animal model, has been undertaken against a background of the sequenced genomes. Strain B-1 is ...
Clostridium difficile infection (CDI) currently affects around 20,000 people each year, in healthcare institutions and in the community, and will often follow disruption of the gut microbiome. Current treatment strategies call for the use of further antibiotics, of which there is a limited choice. There is a need for additional remedial and prophylactic solutions with greater specificity and low levels of toxicity and resistance. This thesis describes the pathogenesis of CDI...
Greenfield, C.; Aguilar Ramirez, J R; Pounder, R E; Williams, T.; Danvers, M; Marper, S R; Noone, P
Stools from 109 patients with inflammatory bowel disease (13.4%) contained Clostridium difficile or its toxin, an incidence similar to the stools of 99 control patients with diarrhoea (11.9%), but significantly higher than the stools of 77 control patients with a normal bowel habit (1.4%). Sixty-six per cent of the diarrhoea controls, but only 11% of the inflammatory bowel disease patients, reported recent antibiotic use: however, 67% of inflammatory bowel disease patients were taking sulphas...
Perry Hookman; Jamie S Barkin
A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to twothirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficileassociated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate
Jasmin Arrich; Gottfried H. Sodeck; Gürkan Seng(o)lge; Christoforos Konnaris; Marcus Müllner; Anton N. Laggner; Hans Domanovits
AIM: Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population.Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea.METHODS: In this case report, we describe the course of Clostridium difficile-associated diarrhea in an 82-yearold patient developing acute renal failure. Stopping the offending agent and symptomatic therapy brought a rapid improvement of diarrhea and acute renal failure, full recovery was gained 18 d after admission. In a systematic review we looked for links between the two conditions.RESULTS: The link between Clostridium difficilr-associated diarrhea and acute renal failure in our patient was most likely volume depletion. However, in experimental studies a direct influence of Clostridium difficile toxins on renal duct cells could be shown.CONCLUSION: Rapid diagnosis, nonspecific supportive treatment and specific antibiotic treatment, especially in the elderly, may lower excess mortality Clostridium difficile-associated diarrhea and renal failure being possible complications.
Full Text Available During the last decade, Clostridium difficile infection showed a dramatic increase in incidence and virulence in the Northern hemisphere. This incessantly challenging disease is the leading cause of antibiotic-associated and nosocomial infectious diarrhea and became life-threatening especially among elderly people. It is generally assumed that all human bacterial pathogens are heterotrophic organisms, being either saccharolytic or proteolytic. So far, this has not been questioned as colonization of the human gut gives access to an environment, rich in organic nutrients. Here, we present data that C. difficile (both clinical and rumen isolates is also able to grow on CO2+H2 as sole carbon and energy source, thus representing the first identified autotrophic bacterial pathogen. Comparison of several different strains revealed high conservation of genes for autotrophic growth and showed that the ability to use gas mixtures for growth decreases or is lost upon prolonged culturing under heterotrophic conditions. The metabolic flexibility of C. difficile (heterotrophic growth on various substrates as well as autotrophy could allow the organism in the gut to avoid competition by niche differentiation and contribute to its survival when stressed or in unfavorable conditions that cause death to other bacteria. This may be an important trait for the pathogenicity of C. difficile.
Banfield Kathleen R
Full Text Available Abstract Background Clostridium difficile-associated diarrhoea (CDAD is a frequently occurring healthcare-associated infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. Environmental contamination is known to play an important contributory role in the spread of CDAD and it is suspected that contamination might be occurring as a result of aerial dissemination of C. difficile spores. However previous studies have failed to isolate C. difficile from air in hospitals. In an attempt to clarify this issue we undertook a short controlled pilot study in an elderly care ward with the aim of culturing C. difficile from the air. Methods In a survey undertaken during February (two days 2006 and March (two days 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control. Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates. Results On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air. One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007. Conclusion This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C
Bolton, R P; Tait, S K; Dear, P R; Losowsky, M. S.
In a prospective survey of infants born in a single maternity unit, asymptomatic faecal colonisation by Clostridium difficile occurred in 31 (47%) of 66 babies who provided a faecal sample during week one of life and at age 14 and 28 days, and in 46 (30.7%) of the total of 150 babies for whom at least one faecal sample was obtained during the month of study. There was no evidence for acquisition of the organism from the mother during delivery and colonisation was unrelated to the means of del...
Gil, Gaby S.; Chaudhari, Shobhana; Shady, Ahmed; Caballes, Ana; Hong, Joe
We report an unusual case of severe diarrhea related to Blastocystis sp. infection in a patient with end stage renal disease on hemodialysis. The patient was admitted due to profuse diarrhea associated with fever and leukocytosis. Pertinent stool work-up such as leukocytes in stool, stool culture, clostridium difficile toxin B PCR, and serology for hepatitis A, hepatitis B, and hepatitis C and cytomegalovirus screening were all negative. Ova and parasite stool examination revealed Blastocystis sp. The patient was given intravenous metronidazole with clinical improvement by day three and total resolution of symptoms by day ten. PMID:27247810
Full Text Available Fernando J Martinez,1 Daniel A Leffler,2 Ciaran P Kelly21Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; 2Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAAbstract: The incidence and severity of Clostridium difficile infection (CDI have increased dramatically over the past decade. Its treatment, however, has largely remained the same with the exception of oral vancomycin use as a first-line agent in severe disease. From 1999 to 2004, 20,642 deaths were attributed to CDI in the United States, almost 7 times the rate of all other intestinal infections combined. Worldwide, several major CDI outbreaks have occurred, and many of these were associated with the NAP1 strain. This ‘epidemic’ strain has contributed to the rising incidence and mortality of CDI. The purpose of this article is to review the current management, treatment, infection control, and prevention strategies that are needed to combat this increasingly morbid disease.Keywords: antibiotic, antimicrobial, infectious colitis, pseudomembranous colitis, nosocomial, iatrogenic, toxin, Clostridium difficile
Lessa, Fernanda C; Gould, Carolyn V; McDonald, L Clifford
The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions. PMID:22752867
Wilson, Kenneth H.; Silva, Joseph; Fekety, F. Robert
Administration of normal cecal homogenates decreased numbers of viable Clostridium difficile and prevented cecitis in antibiotic-challenged hamsters. Cecal anaerobes appeared to suppress C. difficile.
Cartman, Stephen T; Heap, John T; Kuehne, Sarah A; Cockayne, Alan; Minton, Nigel P
The impact of Clostridium difficile-associated disease (CDAD) in healthcare settings throughout the developed world is considerable in terms of mortality, morbidity, and disease management. The incidence of CDAD has risen dramatically since the turn of this century, concomitant with the emergence of so-called hypervirulent strains which are thought to cause a more severe disease, higher relapse rates, and increased mortality. Pre-eminent amongst hypervirulent strains are those belonging to ribotype 027, which were first reported in Canada in 2003 and shortly thereafter in the UK. Since its arrival in Europe, it has spread rapidly and has now been reported in 16 member states and Switzerland. The physiological factors responsible for the rapid emergence of hypervirulent C. difficile strains remain unclear. It is known that they produce a binary toxin (CDT) in addition to toxins A and B, that they are resistant to fluoroquinolones due to mutations in gyrA, and that they are resistant to erythromycin. Representative strains have been suggested to produce more toxin A and B in the 'laboratory flask' (most likely due to a frameshift mutation in the repressor gene tcdC), to be more prolific in terms of spore formation, and also exhibit increased adherence to human intestinal epithelial cells due to altered surface proteins. However, the contribution of these and other as yet unidentified factors to the rapid spread of certain C. difficile variants (e.g., ribotypes 027 and 078) remains unclear at present. The advent of ClosTron technology means that it is now possible to construct genetically stable isogenic mutants of C. difficile and carry out reverse genetic studies to elucidate the role of specific gene loci in causing disease. The identification of virulence factors using this approach should help lead to the rational development of therapeutic countermeasures against CDAD. PMID:20547099
Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospttalized and/or receiving antibiotics; however, community associated infections affecting otherwise healthy individuals have become more ...
Doernberg, Sarah B.; Winston, Lisa G.; Deck, Daniel H.; Chambers, Henry F.
To determine whether doxycycline protects against development of Clostridium difficile infection (CDI), we studied a cohort of adult inpatients who received at least one dose of ceftriaxone. Addition of doxycycline was associated with low risk of CDI.
Schmidt, Nathalie J.; Ho, Helen H.; Dondero, Marjorie E.
A peculiar cytotoxic effect, occasionally encountered in the course of inoculating cell cultures with fecal specimens for routine enterovirus isolation attempts, was shown to be produced by Clostridium difficile toxin.
Tvede, M; Tinggaard, M; Helms, M
Clostridium difficile infection is one of the most common nosocomial infections. Among other alternatives to standard treatment with vancomycin for recurrent infection are faecal microbiota transplantation and rectal bacteriotherapy with a fixed mixture of intestinal bacterial strains isolated from...
Hensgens, M.P.; Keessen, E.C.; Squire, M.M.; Riley, T.V.; Koene, M.G.J.; de Boer, E.; Lipman, L.J.A.; Kuijper, E.J.
Clostridium difficile infections (CDIs) are traditionally seen in elderly and hospitalized patients who have used antibiotic therapy. In the community, CDIs requiring a visit to a general practitioner are increasingly occurring among young and relatively healthy individuals without known predisposin
Hensgens, M.P.M.; Keessen, A.M.; Squire, M.M.; Riley, T.V.; Koene, M.G.J.; Boer, de E.; Lipman, L.J.; Kuijper, E.J.
Clostridium difficile infections (CDIs) are traditionally seen in elderly and hospitalized patients who have used antibiotic therapy. In the community, CDIs requiring a visit to a general practitioner are increasingly occurring among young and relatively healthy individuals without known predisposin
Full Text Available Introduction Clostridium difficile infections predominatelly occur among hospitalized patients. The aim of this study was to evaluate the importance of finding the isolate of Clostridium difficile cultured from the stool of hospitalized patients. Material and methods Material consisted of 100 patients with at least one liquid stool samples and control group with form stool. Every patient spent minimum 48h in hospital before the sampling. The material was immediately cultured on mediums for isolation of enteric pathogens, and on selective CCFA medium (Biomedics for Clostridium difficile in anaerobic condition. Diagnosis of Clostridium difficile toxin in stool samples was achieved by ELISA-RIDASCREEN Clostridium difficile Toxin A/B test (R-Biopharm. Results One-hundred forty one stool samples of patients in Clinical Center Nis were cultivated and examined for C. difficile. The bacteria was isolated in seven patients from the clinical group. In four (57.14% patients, the presence of C. difficile toxin in stool was established. The bacteria was diagnosed from the stool samples of five patients from the control group, but the toxin was not found in their stool samples. Discussion The results performed at the Institute for Public Health Nis are in accordance with previously published results that all patients with positive findings of Clostridium difficile toxin in stool samples were on antibiotic treatment longer than 14 days. By analyzing the patient's stay in hospital and duration of antibiotic treatment, we observed the statistically significant difference in findings between the patients with CDAD and the patients from the control group with positive bacteria. Conclusion The study confirms the importance of finding Clostridium difficile associated disease in four (4% hospitalized patients.
Song, Hyun Joo; Shim, Ki-Nam; Jung, Sung-Ae; Choi, Hee Jung; Lee, Mi Ae; Ryu, Kum Hei; Kim, Seong-Eun; Yoo, Kwon
Backgraound/Aims The direct toxic effects of antibiotics on the intestine can alter digestive functions and cause pathogenic bacterial overgrowth leading to antibiotic-associated diarrhea (AAD). Clostridium Difficile (C. Difficile) is widely known to be responsible for 10~20% of AAD cases. However, Klebsiella oxytoca, Clostridium perfringens, Staphylococcus aureus, and Candida species might also contribute to AAD. Methods We prospectively analyzed the organisms in stool and colon tissue cultu...
Full Text Available Clostridium difficile colitis is a common infection that can be difficult to resolve and may result in recurrent infections. Reactive arthritis is a rare presentation of this disease and its treatment is not well differentiated in the literature. We describe a case of reactive arthritis occurring in a patient with a history of recurrent Clostridium difficile colitis while currently receiving a taper of oral vancomycin. His arthritis symptoms resolved with corticosteroids and continued treatment with anticlostridial antibiotics.
Gougoulias, C.; Tuohy, K.M.; Gibson, G. R.
Clostridium difficile infection is a frequent complication of antibiotic therapy in hospitalised patients, which today is attracting more attention than ever and has led to its classification as a 'superbug'. Disruption of the composition of the intestinal microflora following antibiotic treatment is an important prerequisite for overgrowth of C. difficile and the subsequent development of an infection. Treatment options for antibiotic-associated diarrhoea and C. difficile-induced colitis inc...
Kuijper, Ed J.; Berg, Renate J van den; Debast, Sylvia; Visser, Caroline E; Veenendaal, Dick; Troelstra, Annet; Kooi, Tjallie van der; Hof, Susan van den; Notermans, Daan W.
Outbreaks due to Clostridium difficile polymerase chain reaction (PCR) ribotype 027, toxinotype III, were detected in 7 hospitals in the Netherlands from April 2005 to February 2006. One hospital experienced at the same time a second outbreak due to a toxin A-negative C. difficile PCR ribotype 017 toxinotype VIII strain. The outbreaks are difficult to control.
Sorg, Joseph A.; Sonenshein, Abraham L.
Some cholate derivatives that are normal components of bile can act with glycine to induce the germination of Clostridium difficile spores, but at least one bile component, chenodeoxycholate, does not induce germination. Here we show that chenodeoxycholate inhibits the germination of C. difficile spores in response to cholate and taurocholate.
Kuijper, Ed J; Berg, Renate J van den; Debast, Sylvia; Visser, Caroline E; Veenendaal, Dick; Troelstra, Annet; Kooi, Tjallie van der; Hof, Susan van den; Notermans, Daan W
Outbreaks due to Clostridium difficile polymerase chain reaction (PCR) ribotype 027, toxinotype III, were detected in 7 hospitals in the Netherlands from April 2005 to February 2006. One hospital experienced at the same time a second outbreak due to a toxin A-negative C. difficile PCR ribotype 017 t
Background: Clostridium difficile-associated disease is increasingly reported and studies indicate that food animals may be sources of human infections. Methods: The presence of C. difficile in 345 swine fecal, 1,325 dairy cattle fecal, and 371 dairy environmental samples were examined. Two isolati...
The objective of this study was to compare the prevalence of Clostridium difficile among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Isolation of C. difficile was performed u...
El Feghaly, Rana E.; Stauber, Jennifer L.; Deych, Elena; Gonzalez, Carlos; Tarr, Phillip I.; Haslam, David B.
Fecal inflammatory markers at diagnosis correlate with diarrhea persistence and treatment failure in Clostridium difficile infection, whereas C. difficile fecal bacterial burden does not. C. difficile bacterial concentration decreases similarly in patients treated with metronidazole and vancomycin.
Mohammad Hosain Salari
Full Text Available Abstract Background and objective: Closteridium difficile is a gram positive, anaerobic and spore-forming bacillus. Inflammatory bowel disease or IBD includes Crohn's disease and ulcerative colitis. Inflammation of the intestinal mucosa in these patients can be as a risk factor for colonization of Clostridium difficile. The purpose of this study was to analysis of Clostridium difficile carriage in the IBD outpatients. Materials and methods: Stool specimens were obtained from 50 outpatients with IBD. Stools were cultured on selective media under anaerobic conditions. Filtered extract of bacteria was exposed to HeLa cell culture for analysis of toxin production after identification of Clostridium difficile isolates. Results: The results showed that 3 IBD patients (6% had stool cultures positive for Clostridium difficile. Stool cultures were negative in all patients with Crohn's disease. All 3 patients had ulcerative colitis. Only one isolate was positive for toxin production. Conclusion: The ulcerated colitis than Crohn's patients had higher carriage. In general IBD outpatients carriage rates for Clostridium difficile was low.
Full Text Available Abstract Background Clostridium difficile infection (CDI is an important cause of morbidity and mortality internationally, yet there are important regional differences in the epidemiology and microbiology of disease. Most reports have come from North America and Europe, with limited information from other regions, including the Middle East. Given the changes in the epidemiology of CDI in developed countries, particularly associated with the dissemination of hypervirulent epidemic clones, an understanding of the epidemiology and microbiology of CDI in diverse regions is warranted. This study involved collection of stool samples from individuals with diarrhea at the Isfahan University of Medical Sciences Teaching Hospital, Isfahan, Iran, between October 2010 and March 2011. Selective enrichment culture for C. difficile was performed and isolates were characterised using ribotyping, PCR for the detection of tcdA, tcdB and cdtB genes, and tcdC sequence analysis. Findings Clostridium difficile was isolated from 19/89 (21% stool samples of 17/86 (20% patients. 13/17 (77% cases of CDI were hospital-associated. Patients with CDI were significantly older (43 ± 28y than those with non-CDI diarrhea (24, ± 26y(P = 0.018. All isolates were toxigenic, and possessed genes encoding for toxins A and B. Six (32% of 19 isolates also possessed cdtB. Twelve ribotypes were identified. Ribotype 078/toxinotype V was most common, accounting for 4 (21% of isolates. A single isolate of a different toxinotype V ribotype was identified, as was a toxinotype XXIV isolate. The remaining isolates consisted of 9 different toxinotype 0 ribotypes. Conclusions CDI is an important cause of diarrhea in patients in this hospital. The diversity of ribotypes was striking, and the number of different types suggests the presence of a broad range of strains in the community, the hospital or both. The predominance of toxinotype V strains, which have been associated with community
Doder Radoslava; Kovačević Nadica; Munćan Dragica; Potkonjak Aleksandar; Tomašev Branka; Ružić Maja
Introduction. Clostridium difficile enterocolitis is a potentially fatal disease showing increasing incidence in hospital environment. Therapeutic approach in the management of Clostridium difficile enterocolitis is highly complex, particularly because of its tendency to relapse and reinfection. The study was aimed at investigating the factors influencing the development of Clostridium difficile enterocolitis and outcomes of enterocolitis after administration of standard antimicrobial t...
Full Text Available The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence.
Darkoh, Charles; DuPont, Herbert L.; Norris, Steven J; Heidi B Kaplan
ABSTRACT Clostridium difficile infection (CDI) is dramatically increasing as a cause of antibiotic- and hospital-associated diarrhea worldwide. C. difficile, a multidrug-resistant pathogen, flourishes in the colon after the gut microbiota has been altered by antibiotic therapy. Consequently, it produces toxins A and B that directly cause disease. Despite the enormous public health problem posed by this pathogen, the molecular mechanisms that regulate production of the toxins, which are direct...
Gravisse, J.; Barnaud, G.; Hanau-Berçot, B.; Raskine, L; Riahi, J.; Gaillard, J L; Sanson-Le-Pors, M. J.
Clostridium difficile, the most common cause of antibiotic-associated diarrhea, is occasionally isolated from extraintestinal sites and is usually found as part of a polymicrobial flora. We report a case of brain empyema that occurred after the recurrent intestinal carriage of a nontoxigenic strain of C. difficile. Brain abscess cultures contained both toxigenic and nontoxigenic isolates. Pulsed-field gel electrophoresis showed that nontoxigenic isolates from the intestine and from the brain ...
Cowardin, Carrie A.; Petri, William A, Jr
Clostridium difficile is a Gram-positive, spore forming bacillus and the most common cause of antibiotic-associated diarrhea in the United States. Clinical outcomes of C. difficile infection (CDI) range from asymptomatic colonization to pseudomembranous colitis, sepsis and death. Disease is primarily mediated by the action of the Rho-glucosylating toxins A and B, which induce potent pro-inflammatory signaling within the host. The role of this inflammatory response during infection is just beg...
Lin, Cynthia J.; Wade, Timothy J; Hilborn, Elizabeth D.
Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on...
Jhung, Michael A; Thompson, Angela D; Killgore, George E; Zukowski, Walter E; Songer, Glenn; Warny, Michael; Johnson, Stuart; Gerding, Dale N; McDonald, L Clifford; Limbago, Brandi M
Clostridium difficile is a recognized pathogen in neonatal pigs and may contribute to enteritis in calves. Toxinotype V strains have been rare causes of human C. difficile-associated disease (CDAD). We examined toxinotype V in human disease, the genetic relationship of animal and human toxinotype V strains, and in vitro toxin production of these strains. From 2001 through 2006, 8 (1.3%) of 620 patient isolates were identified as toxinotype V; before 2001, 7 (tcdC deletion and most produced binary toxin. Further study is needed to understand the epidemiology of CDAD caused by toxinotype V C. difficile, including the potential of foodborne transmission to humans. PMID:18598622
Riley, T V; Wymer, V.; Bamford, V. W.; Bowman, R. A.
The isolation rate for Clostridium difficile in diarrhoeal stools was investigated in patients from general practice and community health centres over a 14-month period. C. difficile or its cytotoxin was detected in specimens from 89 (4.7%) of 1882 patients studied and accounted for 30.3% of all enteropathogenic micro-organisms isolated. Overall C. difficile was second only to Giardia lamblia in frequency. Recovery rates in the different groups of patients surveyed varied from 3.6 to 27.5%. T...
Maribeth R. Nicholson
Full Text Available Clostridium difficile is a frequent cause of antibiotic-associated diarrhea in adults and older children. However, as many as 80% of infants can be asymptomatically colonized. The reasons for this have not been well established but are believed to be due to differences in toxin receptors or toxin internalization. Determining which children who test positive for C. difficile warrant treatment is exceedingly difficult, especially in the setting of increased rates of detection and the rising risk of disease in children lacking classic risk factors for C. difficile.
Sommer, Trine Nyboe; Ravn, Pernille; Skinhøj, Ida Elisabeth Gjørup
Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. In 2008, a major outbreak of CD027 took place in North Zealand, Denmark. We described this infection in a single medical department. Patients positive for C. difficile enlisted at Medical...... Department O, Herlev Hospital, in 2009 were included and demographic data were recorded. In total, 69 patients were included, average age 83 years, Charlson Comorbidity Score 4. Of all patients 24 died. Further studies are needed in order to treat and minimize infection with C. difficile....
White, Mary B; Rajagopalan, Shobita; Yoshikawa, Thomas T
Norovirus infection usually results in acute gastroenteritis, often with incapacitating nausea, vomiting, and diarrhea. It is highly contagious and resistant to eradication with alcohol-based hand sanitizer. Appropriate preventative and infection control measures can mitigate the morbidity and mortality associated with norovirus infection. Clostridium difficile infection is the leading cause of health care-associated diarrhea in the United States. Antibiotic use is by far the most common risk factor for C difficile colonization and infection. Appropriate preventive measures and judicious use of antibiotics can help mitigate the morbidity and mortality associated with C difficile infection. PMID:27394020
Over the last years major advances have been made in the field of C. difficile research. Despite the continuous progress of research in C. difficile epidemiology and molecular biology. This thesis shows that the development of molecular based techniques in detecetion and typing of C. difficile could
Clostridium difficile is commonly associated with a spectrum of disease in humans referred to as C. difficile-associated disease (CDAD) and use of antimicrobials is considered a risk factor for development of disease in humans. Clostridium difficile can also inhabit healthy food animals and transmi...
Michael B Francis
Full Text Available Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow these processes to be studied in detail. One such advance is the generation of a mouse-model of C. difficile infection. The development of this system is a major step forward in analyzing the genetic requirements for colonization and infection. While important, it is equally as important in understanding what differences exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination is an important step in C. difficile colonization. Mice produce several different bile acids that are not found in humans. These muricholic acids have the potential to impact C. difficile spore germination. Here we find that the three muricholic acids (α-muricholic acid, β-muricholic acid and ω-muricholic acid inhibit C. difficile spore germination and can impact the growth of vegetative cells. These results highlight an important difference between humans and mice and may have an impact on C. difficile virulence in the mouse-model of C. difficile infection.
Objectives: Since 2003, there has been an emergence of BI/NAP1 strain of Clostridium difficile (Cd) in North American hospitals. The origins of this epidemic strain have yet to be determined. However, PFGE analysis has shown ~80% similarity between this strain and some swine isolates. The objecti...
Recently there has been an epidemic of human disease in North America caused by the bacterium Clostridium difficile (Cd). It appears to be a new strain that is more virulent than previous strains, produces more toxins, and causes more severe disease (McDonald et al., 2005). The origin of the new s...
The incidence and severity of disease associated with toxigenic Clostridium difficile (Cd) have increased in hospitals in North America from the emergence of newer, more virulent strains of Cd. Toxigenic Cd has been isolated from food animals and retail meat with potential implications of transfer ...
Two isolation methods were compared for isolation of Clostridium difficile from food animal feces. The single alcohol shock method (SS) used selective enrichment in cycloserine-cefoxitin fructose broth supplemented with 0.1% sodium taurocholate (TCCFB) followed by alcohol shock and isolation on tryp...
The objective of this study was to compare the prevalence of Clostridium difficile among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Preliminary results are based on 131 C. d...
Dennis D Hedge
Full Text Available 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
Lawson, Paul A; Citron, Diane M; Tyrrell, Kerin L; Finegold, Sydney M
The recent proposal by Lawson and Rainey (2015) to restrict the genus Clostridium to Clostridium butyricum and related species has ramifications for the members of the genera that fall outside this clade that should not be considered as Clostridium sensu stricto. One such organism of profound medical importance is Clostridioides difficile that is a major cause of hospital-acquired diarrhea and mortality in individuals. Based on 16S rRNA gene sequence analysis, the closest relative of Clostridium difficile is Clostridium mangenotii with a 94.7% similarity value and both are located within the family Peptostreptococcaceae that is phylogenetically far removed from C. butyricum and other members of Clostridium sensu stricto. Clostridium difficile is Clostridium mangenotii each produce abundant H2 gas when grown in PYG broth and also produce a range of straight and branched chain saturated and unsaturated fatty acids with C16:0 as a major product. The cell wall peptidoglycan contains meso-DAP as the diagnostic diamino acid. Based on phenotypic, chemotaxonomic and phylogenetic analyses, novel genus Clostridioides gen. nov. is proposed for Clostridium difficile as Clostridioides difficile gen. nov. comb. nov. and that Clostridium mangenotii be transferred to this genus as Clostridioides mangenotii comb. nov. The type species of Clostridioides is Clostridioides difficile. PMID:27370902
Patrick Basu, P.; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N. V.; Mohan, Vinod
Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge.
Guzman, Javier Z; Skovrlj, Branko; Rothenberg, Edward S; Lu, Young; McAnany, Steven; Cho, Samuel K; Hecht, Andrew C; Qureshi, Sheeraz A
Study Design Retrospective database analysis. Objective The purpose of this study is to investigate incidence, comorbidities, and impact on health care resources of Clostridium difficile infection after cervical spine surgery. Methods A total of 1,602,130 cervical spine surgeries from the Nationwide Inpatient Sample database from 2002 to 2011 were included. Patients were included for study based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for cervical spine surgery for degenerative spine diagnoses. Baseline patient characteristics were determined. Multivariable analyses assessed factors associated with increased incidence of C. difficile and risk of mortality. Results Incidence of C. difficile infection in postoperative cervical spine surgery hospitalizations is 0.08%, significantly increased since 2002 (p difficile infection were significantly increased in patients with comorbidities such as congestive heart failure, renal failure, and perivascular disease. Circumferential cervical fusion (odds ratio [OR] = 2.93, p difficile infection after degenerative cervical spine surgery. C. difficile infection after cervical spine surgery results in extended length of stay (p difficile after cervical spine surgery is nearly 8% versus 0.19% otherwise (p difficile to be a significant predictor of inpatient mortality (OR = 3.99, p difficile increases the risk of in-hospital mortality and costs approximately $6,830,695 per year to manage in patients undergoing elective cervical spine surgery. Patients with comorbidities such as renal failure or congestive heart failure have increased probability of developing infection after surgery. Accepted antibiotic guidelines in this population must be followed to decrease the risk of developing postoperative C. difficile colitis. PMID:27190732
Schoster, A.; Kokotovic, Branko; Permin, Anders;
Probiotics have gained importance in human and veterinary medicine to prevent and control clostridial enteric disease. Limited information is available on the ability of different probiotic bacteria used in food products to inhibit Clostridium difficile and Clostridium perfringens. The objective of......) on the reference strains of C. difficile and C. perfringens were assessed by an agar well diffusion assay and by a broth culture inhibition assay using cell-free supernatant harvested at different growth phases, with and without pH neutralization. To study growth characteristics, probiotic strains...... effect as seen when supernatant was assessed with and without pH neutralization. Supernatants obtained from 10 probiotic strains inhibited C. difficile only when supernatant was added without pH neutralization. In the broth culture inhibition assay, growth of C. perfringens and C. difficile was inhibited...
Full Text Available Clostridium difficile infection (CDI is a leading cause of antibiotic-associated diarrhea, a major nosocomial complication. The infective form of C. difficile is the spore, a dormant and resistant structure that forms under stress. Although spore germination is the first committed step in CDI onset, the temporal and spatial distribution of ingested C. difficile spores is not clearly understood. We recently reported that CamSA, a synthetic bile salt analog, inhibits C. difficile spore germination in vitro and in vivo. In this study, we took advantage of the anti-germination activity of bile salts to determine the fate of ingested C. difficile spores. We tested four different bile salts for efficacy in preventing CDI. Since CamSA was the only anti-germinant tested able to prevent signs of CDI, we characterized CamSa's in vitro stability, distribution, and cytotoxicity. We report that CamSA is stable to simulated gastrointestinal (GI environments, but will be degraded by members of the natural microbiota found in a healthy gut. Our data suggest that CamSA will not be systemically available, but instead will be localized to the GI tract. Since in vitro pharmacological parameters were acceptable, CamSA was used to probe the mouse model of CDI. By varying the timing of CamSA dosage, we estimated that C. difficile spores germinated and established infection less than 10 hours after ingestion. We also showed that ingested C. difficile spores rapidly transited through the GI tract and accumulated in the colon and cecum of CamSA-treated mice. From there, C. difficile spores were slowly shed over a 96-hour period. To our knowledge, this is the first report of using molecular probes to obtain disease progression information for C. difficile infection.
Czuprynski, C J; Johnson, W. J.; Balish, E; Wilkins, T
Germfree rats were monoassociated with either a toxin-producing strain of Clostridium difficile (Tox+) or a variant of this strain (ToxR) which produced much less toxin (1/10,000) in vivo and in vitro. Monoassociation of germfree rats with C. difficile Tox+ resulted in mortality (17%) and in pathology to the small and large intestines, livers, and lungs. Cecal filtrates from the Tox+-monoassociated rats were cytotoxic for tissue culture cells. The cytotoxicity of cecal filtrates could be bloc...
Permpoonpattana, Patima; Tolls, Elisabeth H.; Nadem, Ramez; Tan, Sisareuth; Brisson, Alain; Cutting, Simon M.
Clostridium difficile is an important human pathogen and one where the primary cause of disease is due to the transmission of spores. We have investigated the proteins found in the outer coat layers of C. difficile spores of pathogenic strain 630 (CD630). Five coat proteins, CotA, CotB, CotCB, CotD, and CotE, were shown to be expressed on the outer coat layers of the spore. We demonstrate that purified spores carry catalase, peroxiredoxin, and chitinase activity and that this activity correla...
Brazier, Jon S
Unlike other anaerobic bacteria of clinical importance, Clostridium difficile has managed to enter into the realm of public awareness. Following the trail blazed by methicillin-resistant Staphylococcus aureus (MRSA), C. difficile has made the transition from being an obscure anaerobic bacterium, mainly of interest to specialist anaerobic microbiologists, to that of an infamous "superbug" responsible for outbreaks of hospital-acquired infection that commonly result in serious disease and death. This report picks out key moments, particularly in the UK, which tracked the rise in both the public and political awareness of this organism. PMID:22293217
Pancholi, P; Kelly, C; Raczkowski, M; Balada-Llasat, J M
Clostridium difficile is the most important cause of nosocomial diarrhea. Several laboratory techniques are available to detect C. difficile toxins or the genes that encode them in fecal samples. We evaluated the Xpert C. difficile and Xpert C. difficile/Epi (Cepheid, CA) that detect the toxin B gene (tcdB) and tcdB, cdt, and a deletion in tcdC associated with the 027/NAP1/BI strain, respectively, by real-time PCR, and the Illumigene C. difficile (Meridian Bioscience, Inc.) that detects the toxin A gene (tcdA) by loop-mediated isothermal amplification in stool specimens. Toxigenic culture was used as the reference method for discrepant stool specimens. Two hundred prospective and fifty retrospective diarrheal stool specimens were tested simultaneously by the cell cytotoxin neutralization assay (CCNA) and the Xpert C. difficile, Xpert C. difficile/Epi, and Illumigene C. difficile assays. Of the 200 prospective stools tested, 10.5% (n = 23) were determined to be positive by CCNA, 17.5% (n = 35) were determined to be positive by Illumigene C. difficile, and 21.5% (n = 43) were determined to be positive by Xpert C. difficile and Xpert C. difficile/Epi. Of the 50 retrospective stools, previously determined to be positive by CCNA, 94% (n = 47) were determined to be positive by Illumigene C. difficile and 100% (n = 50) were determined to be positive by Xpert C. difficile and Xpert C. difficile/Epi. Of the 11 discrepant results (i.e., negative by Illumigene C. difficile but positive by Xpert C. difficile and Xpert C. difficile/Epi), all were determined to be positive by the toxigenic culture. A total of 21% of the isolates were presumptively identified by the Xpert C. difficile/Epi as the 027/NAP1/BI strain. The Xpert C. difficile and Xpert C. difficile/Epi assays were the most sensitive, rapid, and easy-to use assays for the detection of toxigenic C. difficile in stool specimens. PMID:22278839
Cohen, S H; Tang, Y J; Silva, J
The genes for Clostridium difficile toxins A and B (tcdA and tcdB) are part of a 19.6-kb pathogenicity locus (PaLoc) that includes the genes tcdD, tcdE, and tcdC. To determine whether the C. difficile PaLoc is a stable and conserved genetic unit in toxigenic strains, a multiplex polymerase chain reaction was used to analyze 50 toxigenic, 39 nontoxigenic, and 2 toxin-defective isolates. The respective amplicons were identified for tcdA-E in the toxigenic isolates; these were absent in the nontoxigenic isolates. C. difficile P-829 lacked at least a fragment of tcdD, tcdB, tcdE, and tcdC, but tcdA was present. C. difficile 8864 had deletions in the tcdA and tcdC genes. These data suggest that the PaLoc is highly stable in toxigenic C. difficile, nontoxigenic isolates lack the unit, and isolates with a defective PaLoc can still cause clinical disease. Further studies are needed to define the role of individual genes in the pathogenesis of C. difficile-associated diarrhea. PMID:10669352
Cynthia J. Lin
Full Text Available Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0–6 days, 7–13 days, 14–20 days, and 21–27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19–64 years, ER and outpatient visits for C. difficile infection were elevated during the 7–13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37. This association was more substantial among males (OR = 3.21; 95% CI: 1.01–10.19. Associations during other risk periods were not observed (p < 0.05. Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change.
Clostridium difficile is a pathogen for both humans and animals and is often associated with antibiotic-associated diarrhea. Recently, several human cases of C. difficile-infection with increased mortality and morbidity have been reported. In studies performed in different countries C. difficile has been found in meat. Therefore the question whether C. difficile can be a zoonotic agent has been raised. The aim of this study was to optimize a method for isolation of C. difficile from faeces. W...
Razavi, B; Apisarnthanarak, A; Mundy, L M
Clostridium difficile is a well-known cause of sporadic and healthcare-associated diarrhea. Multihospital outbreaks due to a single strain and outbreaks associated with antibiotic selective pressure, especially clindamycin, have been well documented. Severe cases and fatalities from C. difficile are uncommon. The recent global emergence of a hypervirulent strain containing binary toxin (Toxinotype III ribotype 027), with or without deletion in a regulatory gene (tcdC gene), together with high-level resistance to third generation fluoroquinolones, has been associated with increased morbidity and mortality. Although the defective regulatory gene locus is associated with increased toxin production in vitro, the in vivo significance of this mutation and of the binary toxin remains undefined. To date, treatment strategies have not evolved in response to the emergence of this hypervirulaent strain. We provide a critical, quantitative summary of the evolving clinical and molecular epidemiology of C. difficile along with implications relevant to future treatment strategies. PMID:17885732
Gawlik, Darius; Slickers, Peter; Engelmann, Ines; Müller, Elke; Lück, Christian; Friedrichs, Anette; Ehricht, Ralf; Monecke, Stefan
Background Clostridium difficile can cause antibiotic-associated diarrhea and a possibility of outbreaks in hospital settings warrants molecular typing. A microarray was designed that included toxin genes (tcdA/B, cdtA/B), genes related to antimicrobial resistance, the slpA gene and additional variable genes. Results DNA of six reference strains and 234 clinical isolates from South-Western and Eastern Germany was subjected to linear amplification and labeling with dUTP-linked biotin. Amplicon...
Michael; J; Lipp; Odelya; E; Pagovich; David; Rabin; Albert; D; Min; Brett; B; Bernstein
AIM:To re-evaluate the theory that colonic diverticulosis is associated with relapse of Clostridium difficile associated disease (CDAD) in light of data suggesting increasing rates of CDAD infection and relapse.METHODS: Charts were reviewed for patients with recurrent CDAD who had also had a prior colonoscopy or flexible sigmoidoscopy. An age and gender matched control group was used to compare the prevalence of diverticulosis.RESULTS: Twenty-two patients met the study criteria, and the prevalence of divert...
Govind, Revathi; Vediyappan, Govindsamy; Rolfe, Rial D; Dupuy, Bruno; Fralick, Joe A
Clostridium difficile has been identified as the most important single identifiable cause of nosocomial antibiotic-associated diarrhea and colitis. Virulent strains of C. difficile produce two large protein toxins, toxin A and toxin B, which are involved in pathogenesis. In this study, we examined the effect of lysogeny by PhiCD119 on C. difficile toxin production. Transcriptional analysis demonstrated a decrease in the expression of pathogenicity locus (PaLoc) genes tcdA, tcdB, tcdR, tcdE, and tcdC in PhiCD119 lysogens. During this study we found that repR, a putative repressor gene of PhiCD119, was expressed in C. difficile lysogens and that its product, RepR, could downregulate tcdA::gusA and tcdR::gusA reporter fusions in Escherichia coli. We cloned and purified a recombinant RepR containing a C-terminal six-His tag and documented its binding to the upstream regions of tcdR in C. difficile PaLoc and in repR upstream region in PhiCD119 by gel shift assays. DNA footprinting experiments revealed similarities between the RepR binding sites in tcdR and repR upstream regions. These findings suggest that presence of a CD119-like temperate phage can influence toxin gene regulation in this nosocomially important pathogen. PMID:19776116
Martin, H; Abbott, L P; Low, D E; Willey, B; Mulvey, M; Weese, J Scott
Clostridium difficile is an important cause of disease in Canada; however, little information is available about the disease in the Maritime provinces. The objective of the present study was to characterize C difficile isolates obtained from people hospitalized with C difficile infection in Prince Edward Island. One hundred twenty-six C difficile ELISA toxin-positive stool samples were obtained and cultured using an enrichment protocol. C difficile was isolated from 105 of 126 (83%) samples. Twenty-two different ribotypes were identified. The most common ribotype, ribotype W, was a North American pulsotype 2 (NAP2), toxinotype 0 strain, which represented 18% of isolates. The next most common ribotype was a NAP1, toxinotype III strain, which accounted for 11% of isolates. Ribotype 027/NAP1 only accounted for five (4.7%) isolates. Forty-five per cent of isolates possessed genes encoding production of binary toxin. Three different ribotypes, all NAP1, toxinotype III strains, had a frameshift mutation in the tcdC gene (Delta117), while one isolate (ribotype 078, NAP4, toxinotype V) had a truncating mutation (C184T) in the tcdC gene. PMID:19436570
Silva, Rodrigo Otávio Silveira; D'elia, Mirella Lauria; de Magalhães Soares, Danielle Ferreira; Cavalcanti, Álvaro Roberto; Leal, Rodrigo Costa; Cavalcanti, Guilherme; Pereira, Pedro Lúcio Lithg; Lobato, Francisco Carlos Faria
The aim of this study is to report a case of Clostridium difficile-associated diarrhea in an ocelot (Leopardus pardalis) in the state of Mato Grosso do Sul, Brazil. The animal, a 24-month-old male, was referred to the Centro de Reabilitação de Animais Silvestres (CRAS) with a history of having been run over and tibia and fibula fractures. After a surgery to repair the fractures, the ocelot underwent antibiotic therapy with two doses of sodium cefovecin, during which he presented with diarrhea. A stool sample was positive for A/B toxins by a cytotoxicity assay, and a toxigenic strain of C. difficile was isolated. No other enteropathogens were detected. The association between the history, clinical signs and laboratory exams confirmed the diagnosis of C. difficile-associated diarrhea. The present report confirms C. difficile as a potential pathogen for wild felids and suggests that the C. difficile-associated diarrhea should be considered in diarrhea cases, especially when the clinical signs began after antimicrobial use. PMID:23467074
Pye, Hayley; Kohoutova, Darina; Mosse, Charles A.; Yahioglu, Gokhan; Stamati, Ioanna; Deonarain, Mahendra; Battah, Sinan; Ready, Derren; Allan, Elaine; Mullany, Peter; Lovat, Laurence B.
Background Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections. Methods PACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29. Results Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT. Conclusion This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon. PMID:26313448
Luisa De Sordi
Full Text Available Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT could be used as a novel approach to treating C. difficile infections.PACT utilises the ability of light-activated photosensitisers (PS to produce reactive oxygen species (ROS such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29.Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2 without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT.This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
Riccobono, E; Di Pilato, V; Della Malva, N; Meini, S; Ciraolo, F; Torricelli, F; Rossolini, G M
Clostridium difficile, belonging to ribotype 018 (RT018), is one of the most prevalent genotypes circulating in hospital settings in Italy. Here, we report the draft genome of C. difficile CD8-15 belonging to RT018, isolated from a patient with fatal C. difficile-associated infection. PMID:27587821
Dominguez, Samuel R; Dolan, Susan A; West, Kelly; Dantes, Raymund B; Epson, Erin; Friedman, Deborah; Littlehorn, Cynthia A; Arms, Lesley E; Walton, Karen; Servetar, Ellen; Frank, Daniel N; Kotter, Cassandra V; Dowell, Elaine; Gould, Carolyn V; Hilden, Joanne M; Todd, James K
Surveillance testing for Clostridium difficile among pediatric oncology patients identified stool colonization in 29% of patients without gastrointestinal symptoms and in 55% of patients with prior C. difficile infection (CDI). A high prevalence of C. difficile colonization and diarrhea complicates the diagnosis of CDI in this population. PMID:24785235
Cappella, Michela; Pugliese, Fabrizio; Zucchini, Andrea; Marchetti, Federico
Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered. PMID:27190666
Full Text Available Reactive arthritis is a rare complication of Clostridium difficile enterocolitis, especially in children. We review the 6 pediatric cases published in the English and non-English literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. We also report the seventh case of Clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. After the antibiotic course, the child developed at the same time diarrhea with positive stool culture for Clostridium difficile and an asymmetric polyarthritis. Nonsteroidal anti-inflammatory drugs and metronidazole completely resolved the pain, joint swelling, and diarrhea. After twelve months of follow-up there has been no recurrence. This report confirms the self-limiting course of Clostridium difficile reactive arthritis. Clostridium difficile testing in children with gastrointestinal symptoms and acute onset of joint pain should be always considered.
Alqumber, Mohammed A
Objectives: To determine Clostridium difficile (C. difficile) prevalence on retail surfaces and shoppers plastic bags. Methods: From 20 June to 10 August 2011, in a cross-sectional epidemiological study, 17 supermarkets from 2 cities, Albaha and Altaif, Saudi Arabia were sampled. A total of 800 samples, which comprised 200 samples per surveyed surface, were studied. These included baskets, trolleys, conveyer belts, and outgoing shoppers’ plastic bags. Clostridium difficile strains were isolat...
Aspinall, S T; Dealler, S. F.
AIMS: A set of five tests were developed and tested for their ability to confirm the identity of C difficile colonies within 30 minutes. METHODS: The relevant substrates were incorporated into four filter paper squares attached to a plastic carrier (Diffstrip), five enzymes/products (prolyl aminopeptidase, galactosidase, leucine aminopeptidase, acid phosphatase and indole). The strips were inoculated, incubated for 20 minutes, and reagents added. RESULTS: 96.4% (212 of 220) strains of C diffi...
Zaiß, Henning; Witte, Wolfgang; Nübel, Ulrich
We characterized 670 Clostridium diffi cile isolates collected from patients in 84 hospitals in Germany in 2008. PCR ribotyping showed high prevalence of ribotype 001 and restricted dissemination of ribotype 027 strains. Fluoroquinolone resistance and associated gyrase mutations were frequent in various ribotypes, but no resistance to metronidazole or vancomycin was noted.
Wroblewski, Danielle; Hannett, George E; Bopp, Dianna J; Dumyati, Ghinwa K; Halse, Tanya A; Dumas, Nellie B; Musser, Kimberlee A
Our laboratory has developed testing methods that use real-time PCR and pyrosequencing analysis to enable the rapid identification of potential hypervirulent Clostridium difficile strains. We describe a real-time PCR assay that detects four C. difficile genes encoding toxins A (tcdA) and B (tcdB) and the binary toxin genes (cdtA and cdtB), as well as a pyrosequencing assay that detects common deletions in the tcdC gene in less than 4 h. A subset of historical and recent C. difficile isolates (n = 31) was also analyzed by pulsed-field gel electrophoresis to determine the circulating North American pulsed-field (NAP) types that have been isolated in New York State. Thirteen different NAP types were found among the 31 isolates tested, 13 of which were NAP type 1 strains. To further assess the best approach to utilizing our conventional and molecular methods, we studied the populations of C. difficile in patient stool specimens (n = 23). Our results indicated that 13% of individual stool specimens had heterogeneous populations of C. difficile when we compared the molecular characterization results for multiple bacterial isolates (n = 10). Direct molecular analysis of stool specimens gave results that correlated well with the results obtained with cultured stool specimens; the direct molecular analysis was rapid, informative, and less costly than the testing of multiple patient stool isolates. PMID:19403775
Lin, Y-C; Huang, Y-T; Lee, T-F; Lee, N-Y; Liao, C-H; Lin, S-Y; Ko, W-C; Hsueh, P-R
The medical records of 84 patients with stool cultures positive for Clostridium difficile during the period August 2007 to June 2009 were retrospectively reviewed. A case of confirmed (toxigenic)C. difficile infection (CDI) was defined by the presence of symptoms (fever, diarrhoea, abdominal discomfort or distension, ileus) and the presence of toxigenic C. difficile. Patients with compatible clinical symptoms and stool cultures positive for non-toxigenic C. difficile isolates were defined as probable (non-toxigenic) CDI cases. Of these 84 patients, 50 (59.5%) were diagnosed as confirmed CDI and 34 (40.5%) as probable CDI. Thirteen (15.5%) of the 84 patients died during their hospital stay. Usage of proton pump inhibitors was a significant independent risk factor for CDI (OR 3.21, P=0.014). Of the 50 isolates associated with confirmed CDI, seven (8.3%) carried binary toxin genes (cdtAB), and six (7.1%) had a deletion in the tcdC gene. The mortality rate in confirmed CDI patients with isolates exhibiting deletion in the tcdC gene (2/6, 33.3%), those with isolates harbouring binary toxin genes (2/7, 28.6%), and those with isolates containing mutations in gyrA (2/7, 28.6%) and gyrB (1/2, 50%) was higher than the overall mortality rate (10/50, 20%) in patients with confirmed CDI. PMID:23218131
Antikainen, Jenni; Pasanen, Tanja; Mero, Sointu; Tarkka, Eveliina; Kirveskari, Juha; Kotila, Saara; Mentula, Silja; Könönen, Eija; Virolainen-Julkunen, Anni-Riitta; Vaara, Martti; Tissari, Päivi
Clostridium difficile strains belonging to the PCR ribotype 027, pulse-field gel electrophoresis (PFGE) type NAP1, toxinotype III and restriction endonuclease analysis group BI harbouring mutations in the tcdC gene and possessing binary toxin components A and B have been described to cause epidemics with increased morbidity and mortality. In the present study we developed a conventional multiplex PCR designed to detect selected virulence associated markers of the hypervirulent C. difficile PCR ribotype 027. The multiplex PCR assay detected the major toxins A and B, binary toxin components A and B as well as a possible deletion in the tcdC gene: a characteristic pattern of amplification products for the PCR ribotype 027 strains was detected. This rather simple method was specific for the screening of this hypervirulent C. difficile strain. The correlation between the multiplex PCR and PCR ribotyping methods was excellent. The sensitivity and specificity were 100% in our epidemiological situation. In conclusion, this multiplex PCR was found useful in the preliminary screening for the hypervirulent C. difficile PCR ribotype 027. PMID:19664132
Martin-Verstraete, Isabelle; Peltier, Johann; Dupuy, Bruno
The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection. PMID:27187475
Martin, Jessica S H; Monaghan, Tanya M; Wilcox, Mark H
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. PMID:26956066
Riley, Thomas V; Thean, Sarah; Hool, Graham; Golledge, Clayton L
We report the first isolation in Australia of a hypervirulent epidemic strain of Clostridium difficile, PCR ribotype 027. It was isolated from a 43-year-old woman with a permanent ileostomy, who appears to have been infected while travelling in the United States. The isolate was positive for toxin A, toxin B and binary toxin, and resistant to fluoroquinolone antimicrobials, and had characteristic deletions in the tcdC gene. All diagnostic laboratories and health care facilities in Australia should now be on high alert for this organism. PMID:19527210
Fu, Nancy; Wong, Titus
Clostridium difficile infection (CDI) is now the leading cause of nosocomial infection. There has been an upsurge of CDI in patients with inflammatory bowel disease (IBD). IBD patients with CDI have increased morbidity and mortality. The establishment, proliferation, and recurrence of CDI in IBD patients form a complex interplay of microbial, environmental, and host-susceptibility factors. Different risk factors have been found predisposing IBD patients to CDI. Vancomycin performs better than metronidazole in treating IBD patients with CDI. Fecal microbiota transplantation continues to be a very effective therapy. New therapeutic modalities such as vaccinations and bile salts are currently being investigated. PMID:27137789
Surawicz, Christina M.
Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.
Lees, E A; Miyajima, F; Pirmohamed, M; Carrol, E D
Clostridium difficile is an important nosocomial pathogen in adults. Its significance in children is less well defined, but cases of C. difficile infection (CDI) appear to be increasingly prevalent in paediatric patients. This review aims to summarize reported Clostridium difficile carriage rates across children of different age groups, appraise the relationship between CDI and factors such as method of delivery, type of infant feed, antibiotic use, and co-morbidities, and review factors affecting the gut microbiome in children and the host immune response to C. difficile. Searches of PubMed and Google Scholar using the terms 'Clostridium difficile neonates' and 'Clostridium difficile children' were completed, and reference lists of retrieved publications screened for further papers. In total, 88 papers containing relevant data were included. There was large inter-study variation in reported C. difficile carriage rates. There was an association between CDI and recent antibiotic use, and co-morbidities such as immunosuppression and inflammatory bowel disease. C. difficile was also found in stools of children with diarrhoea attributed to other pathogens (e.g. rotavirus). The role of C. difficile in the paediatric gut remains unclear; is it an innocent bystander in diarrhoeal disease caused by other organisms, or a pathogen causing subclinical to severe symptoms? Further investigation of the development of serological and local host response to C. difficile carriage may shed new light on disease mechanisms. Work is underway on defining a framework for diagnosis and management of paediatric CDI. PMID:27107991
Full Text Available Clostridium difficile is currently one of the most common cause of diarrhea in hospitalized or residents in long term care institutions patients, symptoms of infection ranging from diarrhea to pseudo-membranous colitis and toxic megacolon.The disease is due to the production of enterotoxin A, cytotoxin B or binary toxin. The emergence of hypervirulent new strains showing a tcdC regulatory gene deletion (ribotype 027 has been observed in recent years. Stool or rectal swab specimens were screened using automated real-time multiplex PCR (GeneXpert, Cellbio to detect the presence of toxins producing (B toxin, binary toxin and tcdC gene deletion C. difficile. All positive samples were cultured in order to isolate the causing infection strains.The binary toxin and/or tcdC deletion producing strains were genotyped using Multilocus Sequence Typing (MLST. MLST compares the intragenic sequences of seven housekeeping genes and provides a unique combination of alleles; to each combination is then assigned a Sequence Typing (ST. In the period January 2010 – June 2011, 3681 samples from 2234 patients were analyzed. Four hundred seventy-three patients (21.2% were positive for the presence of C. difficile, 34 (7.2% of there were also positive for binary toxin and 3 were positive for the tcdC gene deletion (suspected C. difficile NAP027.All the strains having tcdC gene deletion, showes ST3 typing by MLST method.These strains were isolated during the same period. The three patiens were epidemiologically linked: the patient A was hospitalized in the same room of patient B, while patient C was managed by the same team care of patient A.The spread ofsuch C. difficile strains is at the present very low in Italy. Our data confirm the poor prevalence of ribotype NAP027 and the usefulness of a presumptive diagnosis to implement immediately appropriate control measures.
Liu, Ji; Zhang, Bei-Lei; Sun, Chun-Li; Wang, Jun; Li, Shan; Wang, Ju-Fang
High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection. PMID:27151296
Nagaro, Kristin J.; Phillips, S. Tyler; Cheknis, Adam K.; Sambol, Susan P.; Zukowski, Walter E.; Johnson, Stuart; Gerding, Dale N.
Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 106 CFU of spores of NTCD ...
Dobreva, Elina G; Ivanov, Ivan N; Vathcheva-Dobrevska, Rossitza S; Ivanova, Katucha I; Asseva, Galina D; Petrov, Petar K; Kantardjiev, Todor V
The increasing incidence of Clostridium difficile infection (CDI) in Bulgaria has indicated the need to implement better surveillance approaches. The aim of the present work was to improve the current surveillance of CDI in Bulgaria by introducing innovative methods for identification and typing. One hundred and twenty stool samples obtained from 108 patients were studied over 4 years from which 32 C. difficile isolates were obtained. An innovative duplex EvaGreen real-time PCR assay based on simultaneous detection of the gluD and tcdB genes was developed for rapid C. difficile identification. Four toxigenic profiles were distinguished by PCR: A(+)B(+)CDT(-) (53.1 %, 17/32), A(-)B(+)CDT(-) (28.1 %, 9/32), A(+)B(+)CDT(+) (9.4 %, 3/32) and A(-)B(-)CDT(-) (9.4 %, 3/32). PCR ribotyping and multilocus variable number of tandem repeat analysis (MLVA7) were used for molecular characterization of the isolates. In total, nine distinct ribotypes were confirmed and the most prevalent for Bulgarian hospitals was 017 followed by 014/020, together accounting for 44 % of all isolates. Eighteen per cent of the isolates (6/32) did not match any of the 25 reference ribotypes available in this study. Twenty-four MLVA7 genotypes were detected among the clinical C. difficile isolates, distributed as follows: five for 017 ribotype, two for 014/020, 001, 002, 012 and 046 each, and one each for ribotypes 023, 070 and 078. The correlation between the typing methods was significant and allowed the identification of several clonal complexes. These results suggest that most C. difficile cases in the eight Bulgarian hospitals studied were associated with isolates belonging to the outbreak ribotypes 017 and 014/20, which are widely distributed in Europe. The real-time PCR protocol for simultaneous detection of gluD and tcdB proved to be very effective and improved C. difficile identification and confirmation of clinical C. difficile isolates. PMID:23598377
Essenmacher, Alex C.; Khurram, Nazish; Bismack, Gregory T.
Reactive arthritis is an acute, aseptic, inflammatory arthropathy following an infectious process but removed from the site of primary infection. It is often attributed to genitourinary and enteric pathogens, such as Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia, in susceptible individuals. An uncommon and less recognized cause of this disease is preceding colonic infection with Clostridium difficile, an organism associated with pseudomembranous colitis and diarrhea in hospitalized patients and those recently exposed to antibiotics. Recognition of this association may be complicated by non-specific presentation of diarrhea, the interval between gastrointestinal and arthritic symptoms, and the wide differential in mono- and oligoarthritis. We present the case of a 61-year-old, hospitalized patient recently treated for C. difficile colitis who developed sudden, non-traumatic, right knee pain and swelling. Physical examination and radiographs disclosed joint effusion, and sterile aspiration produced cloudy fluid with predominant neutrophils and no growth on cultures. Diagnostic accuracy is enhanced by contemporaneous laboratory investigations excluding other entities such as gout and rheumatoid arthritis and other infections that typically precede reactive arthritis. Contribution of Clostridium infection to reactive arthritis is an obscure association frequently difficult to prove, but this organism is warranted inclusion in the differential of reactive arthritis. PMID:26908381
Clostridium difficile (C. difficile) infection (CDI) is the most common cause of -healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value. PMID:27065726
Olsen, Margaret A.; Dubberke, Erik R.; Galvani, Alison P.; Townsend, Jeffrey P.
To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2–32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%–51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%–0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions. PMID:26982504
Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value. PMID:27065726
Full Text Available The epidemiology of Clostridium difficile infections (CDI has changed over the past decade. In addition to dramatic worldwide increases in incidence, new CDI populations are emerging. These populations include patients with community acquired infections with no previous antibiotic exposure, children, pregnant women and patients with IBD. Diagnosis of CDIs requires the identification of C. difficile toxin A or B in diarrheal stool. Current diagnostic tests, however, remains inadequate and an optimal diagnostic testing algorithm has not yet been defined. Metronidazole and vancomycin are currently first-line agents for CDI treatment. Vancomycine, however, has demonstrated superior efficacy and therefore is the preferred agent in patients with severe infections. As with many antibiotics, the incidence of treatment failure with metronidazole is increasing, thereby emphasizing the need to find alternative treatments. Disease recurrence continues to occur in 20-40% of patients and its treatment remains challenging. In patients who develop fulminant colitis from a CDI, early surgical consultation is essential. Intravenous immunoglobulin and tigecycline have been used in patients with severe refractory disease, however delaying surgery may be associated with worse outcomes. Due to the risk of horizontal transmission of C.difficile infection control measures are necessary. Animals may serve as reservoirs for humans. Ongoing research by human and veterinary scientist into, epidemiology, diagnosis, effective treatment protocols and prevention are essential.
Galdys, Alison L; Nelson, Jemma S; Shutt, Kathleen A; Schlackman, Jessica L; Pakstis, Diana L; Pasculle, A William; Marsh, Jane W; Harrison, Lee H; Curry, Scott R
Previous studies suggested that 7 to 15% of healthy adults are colonized with toxigenic Clostridium difficile. To investigate the epidemiology, genetic diversity, and duration of C. difficile colonization in asymptomatic persons, we recruited healthy adults from the general population in Allegheny County, Pennsylvania. Participants provided epidemiological and dietary intake data and submitted stool specimens. The presence of C. difficile in stool specimens was determined by anaerobic culture. Stool specimens yielding C. difficile underwent nucleic acid testing of the tcdA gene segment with a commercial assay; tcdC genotyping was performed on C. difficile isolates. Subjects positive for C. difficile by toxigenic anaerobic culture were asked to submit additional specimens. One hundred six (81%) of 130 subjects submitted specimens, and 7 (6.6%) of those subjects were colonized with C. difficile. Seven distinct tcdC genotypes were observed among the 7 C. difficile-colonized individuals, including tcdC genotype 20, which has been found in uncooked ground pork in this region. Two (33%) out of 6 C. difficile-colonized subjects who submitted additional specimens tested positive for identical C. difficile strains on successive occasions, 1 month apart. The prevalence of C. difficile carriage in this healthy cohort is concordant with prior estimates. C. difficile-colonized individuals may be important reservoirs for C. difficile and may falsely test positive for infections due to C. difficile when evaluated for community-acquired diarrhea caused by other enteric pathogens. PMID:24759727
Girinathan, Brintha Parasumanna; Braun, Sterling; Sirigireddy, Apoorva Reddy; Lopez, Jose Espinola; Govind, Revathi
Clostridium difficile is the principal cause of antibiotic-associated diarrhea. Major metabolic requirements for colonization and expansion of C. difficile after microbiota disturbance have not been fully determined. In this study, we show that glutamate utilization is important for C. difficile to establish itself in the animal gut. When the gluD gene, which codes for glutamate dehydrogenase (GDH), was disrupted, the mutant C. difficile was unable to colonize and cause disease in a hamster model. Further, from the complementation experiment it appears that extracellular GDH may be playing a role in promoting C. difficile colonization and disease progression. Quantification of free amino acids in the hamster gut during C. difficile infection showed that glutamate is among preferred amino acids utilized by C. difficile during its expansion. This study provides evidence of the importance of glutamate metabolism for C. difficile pathogenesis. PMID:27467167
Dailey, D C; Schloemer, R H
The feasibility of the cloning and expression of Clostridium difficile antigens in Escherichia coli was investigated. The expression of a limited number of cloned clostridial antigens under the control of clostridial promoter elements in E. coli was observed.
Rasmussen, Torsten Bloch; Friis, Mikkel Lønborg; Lehnhoff, Rudolf;
severe colonic dilation, inflammation and oedema consistent with toxic megacolon. Stool samples were positive for Clostridium difficile. Oral vancomycine treatment and colonic decompression were inefficient. Subtotal colectomy was performed after which the condition improved. Udgivelsesdato: 2008-May-5...
Debast, Sylvia Brigitte
Since a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea, associated with an increased duration of hospitalization, healthcare expenses, morbidity and mortality. Thi
Kuehne, Sarah A; Cartman, Stephen T; Minton, Nigel P.
The bacterium Clostridium difficile is the leading cause of healthcare associated diarrhoea in the developed world and thus presents a major financial burden. The main virulence factors of C. difficile are two large toxins, A and B. Over the years there has been some debate over the respective roles and importance of these two toxins. To address this, we recently constructed stable toxin mutants of C. difficile and found that they were virulent if either toxin A or toxin B was functional. Thi...
Dominador Lao; Tom Chiang; Eric Gomez
The occurrence of Clostridium difficile colitis is on the rise and has become more difficult to manage with standard therapy. Thus, the need for alternative treatments is essential. Tigecycline is a glycylcycline antibiotic that has been shown to be effective against C. difficile through several published case reports and in in vitro studies. We present a case of C. difficile colitis that failed to respond to metronidazole and oral vancomycin therapy, but improved on a combination of rifaximi...
Lalande, Valérie; Barrault, Laurence; Wadel, Sophie; Eckert, Catherine; Petit, Jean-Claude; Barbut, Frédéric
A new assay (illumigene C. difficile; Meridian Bioscience), based on the original loop-mediated isothermal amplification (LAMP) assay, was evaluated with 472 unformed stools from patients suspected of Clostridium difficile infection. Compared to the toxigenic culture, the sensitivity, specificity, and positive and negative predictive values were 91.8, 99.1, 91.8, and 99.1% for the illumigene C. difficile assay and 69.4, 100, 100, and 96.6% for the cytotoxicity assay, respectively.
Lalande, Valérie; Barrault, Laurence; Wadel, Sophie; Eckert, Catherine; Petit, Jean-Claude; Barbut, Frédéric
A new assay (illumigene C. difficile; Meridian Bioscience), based on the original loop-mediated isothermal amplification (LAMP) assay, was evaluated with 472 unformed stools from patients suspected of Clostridium difficile infection. Compared to the toxigenic culture, the sensitivity, specificity, and positive and negative predictive values were 91.8, 99.1, 91.8, and 99.1% for the illumigene C. difficile assay and 69.4, 100, 100, and 96.6% for the cytotoxicity assay, respectively. PMID:21525213
Antharam, Vijay C.; Li, Eric C.; Ishmael, Arif; Sharma, Anuj; Mai, Volker; Rand, Kenneth H.; Wang, Gary P.
Clostridium difficile infection (CDI) causes nearly half a million cases of diarrhea and colitis in the United States each year. Although the importance of the gut microbiota in C. difficile pathogenesis is well recognized, components of the human gut flora critical for colonization resistance are not known. Culture-independent high-density Roche 454 pyrosequencing was used to survey the distal gut microbiota for 39 individuals with CDI, 36 subjects with C. difficile-negative nosocomial diarr...
Ackermann, Grit; Tang, Yajarayma J.; Kueper, Robert; Heisig, Peter; Arne C Rodloff; Silva, Joseph; Cohen, Stuart H.
Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for...
Sponseller, Jerlyn K.; Steele, Jennifer A.; Schmidt, Diane J.; Kim, Hyeun Bum; Beamer, Gillian; Sun, Xingmin; Tzipori, Saul
Background. Clostridium difficile is a primary cause of antibiotic-associated diarrhea that typically develops when gut microbiota is altered. Conventional treatment for C. difficile infection (CDI) is additional antimicrobial administration, which further disrupts normal intestinal microbiota, often resulting in poor treatment outcomes.
Carman, Robert J.; Boone, James H.; Grover, Harish; Wickham, Kimberly N.; Chen, Li
We report the selection of Clostridium difficile resistant to the rifamycin class of antibiotics in a patient within 32 h of receiving rifaximin for the treatment of recurrent C. difficile diarrhea. Resistance was associated with single nucleotide substitutions within rpoB.
A comparative study was performed to determine the accuracy of Clostridium difficile toxin detection. A commercial cytotoxicity assay (Bartels Immunodiagnostic Supply, Bellevue, Wash.) was compared with conventional microcytotoxicity assays, using Vero and MRC-5 cells. The Bartels system was found to be essentially equivalent to conventional cytotoxicity assays currently being performed for routine C. difficile toxin detection.
Dhalla, Irfan A.; Muhammad M Mamdani; Simor, Andrew E; Kopp, Alex; Rochon, Paula A; Juurlink, David N.
Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause Clostridium difficile-associated disease than levofloxacin. In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of C. difficile-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin.
S. Svraka-Latifovic (Sanela); E. Kuijper; E. Duizer (Erwin); D. Bakker; M.P.G. Koopmans D.V.M. (Marion)
textabstractThe coincidental increase in norovirus outbreaks and Clostridium difficile infection (CDI) raised the question of whether these events could be related, e.g. by enhancing spread by diarrhoeal disease outbreaks. Therefore, we studied the prevalence of C. difficile in outbreaks of viral ga
Søes, Lillian Marie; Holt, H M; Böttiger, B;
SUMMARY To identify risk factors for Clostridium difficile infection (CDI) in Danish patients consulting general practice with gastrointestinal symptoms, a prospective matched case-control study was performed; cases (N = 259) had positive cultures for toxigenic C. difficile and controls (N = 455...
The incidence and severity of disease associated with toxigenic Clostridium difficile have increased in hospitals in North America with the emergence of newer, more virulent strains. Toxigenic C. difficile has been isolated from food animals and retail meat with potential implications of transfer t...
Heslop, Orville D; Roye-Green, Karen; Coard, Kathleen; Mulvey, Michael R
Background Clostridium difficile is the major cause of nosocomial antibiotic-associated diarrhoea with the potential risk of progressing to severe clinical outcomes including death. It is not unusual for Clostridium difficile infection to progress to complications of toxic megacolon, bowel perforation and even Gram-negative sepsis following pathological changes in the intestinal mucosa. These complications are however less commonly seen in community-acquired Clostridium difficile infection th...
Bartsch, S M; Curry, S R; Harrison, L H; Lee, B Y
Asymptomatic Clostridium difficile carriage has a prevalence reported as high as 51-85 %; with up to 84 % of incident hospital-acquired infections linked to carriers. Accurately identifying carriers may limit the spread of Clostridium difficile. Since new technology adoption depends heavily on its economic value, we developed an analytic simulation model to determine the cost-effectiveness screening hospital admissions for Clostridium difficile from the hospital and third party payer perspectives. Isolation precautions were applied to patients testing positive, preventing transmission. Sensitivity analyses varied Clostridium difficile colonization rate, infection probability among secondary cases, contact isolation compliance, and screening cost. Screening was cost-effective (i.e., incremental cost-effectiveness ratio [ICER] ≤ $50,000/QALY) for every scenario tested; all ICER values were ≤ $256/QALY. Screening was economically dominant (i.e., saved costs and provided health benefits) with a ≥10.3 % colonization rate and ≥5.88 % infection probability when contact isolation compliance was ≥25 % (hospital perspective). Under some conditions screening led to cost savings per case averted (range, $53-272). Clostridium difficile screening, coupled with isolation precautions, may be a cost-effective intervention to hospitals and third party payers, based on prevalence. Limiting Clostridium difficile transmission can reduce the number of infections, thereby reducing its economic burden to the healthcare system. PMID:22752150
Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger
The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629
Kachrimanidou, Melina; Sarmourli, Theopisti; Skoura, Lemonia; Metallidis, Symeon; Malisiovas, Nikolaos
Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development. PMID:25955884
Beacher, N; Sweeney, M P; Bagg, J
Dentists prescribe significant volumes of antimicrobial drugs within primary care settings. There is good evidence that many of the prescriptions are not justified by current clinical guidance and that that there is considerable misuse of these drugs in dentistry. One of the risks associated with antibiotic administration is Clostridium difficile-associated disease (CDAD), an entity of which many healthcare workers, including dentists, have little knowledge or understanding. This review seeks to identify the extent and nature of the problem and provides an up to date summary of current views on CDAD, with particular reference to community acquired disease. As for all healthcare workers, scrupulous attention to standard infection control procedures and reducing inappropriate antibiotic prescribing are essential to reduce the risks of CDAD, prevent emergence of further resistant strains of microorganisms and maintain the value of the arsenal of antibiotics currently available to us. PMID:26404991
Masao Hashimoto; Yasuhiko Sugawara; Sumihito Tamura; Junichi Kaneko; Yuichi Matsui; Junichi Togashi; Masatoshi Makuuchi
AIM: To assess the incidence and analyze the risk factors for Clostridium difficile-associated diarrhea (CDAD)after living donor liver transplantation (LDLT) in adult.METHODS: The micobiological data and medical records of 242 adult recipients that underwent LDLT at the Tokyo University Hospital were analyzed retrospectively. The independent risk factors for postoperative CDAD were identified.RESULTS: Postoperative CDAD occurred in 11 (5%)patients. Median onset of CDAD was postoperative d 19(range, 5-54). In the multivariate analyses, male gender (odds ratio, 4.56) and serum creatinine (≥ 1.5 mg/dL,odds ratio, 16.0) independently predicted postoperative CDAD.CONCLUSION: CDAD should be considered in the differential diagnosis of patients with postoperative diarrhea after LDLT.
Pruitt, Rory N.; Chumbler, Nicole M.; Rutherford, Stacey A.; Farrow, Melissa A.; Friedman, David B.; Spiller, Ben; Lacy, D. Borden (Vanderbilt)
The principle virulence factors in Clostridium difficile pathogenesis are TcdA and TcdB, homologous glucosyltransferases capable of inactivating small GTPases within the host cell. We present crystal structures of the TcdA glucosyltransferase domain in the presence and absence of the co-substrate UDP-glucose. Although the enzymatic core is similar to that of TcdB, the proposed GTPase-binding surface differs significantly. We show that TcdA is comparable with TcdB in its modification of Rho family substrates and that, unlike TcdB, TcdA is also capable of modifying Rap family GTPases both in vitro and in cells. The glucosyltransferase activities of both toxins are reduced in the context of the holotoxin but can be restored with autoproteolytic activation and glucosyltransferase domain release. These studies highlight the importance of cellular activation in determining the array of substrates available to the toxins once delivered into the cell.
Alison C Pitts
Full Text Available Bacterial microcompartments form a protective proteinaceous barrier around metabolic enzymes that process unstable or toxic chemical intermediates. The genome of the virulent, multidrug-resistant Clostridium difficile 630 strain contains an operon, eut, encoding a bacterial microcompartment with genes for the breakdown of ethanolamine and its utilisation as a source of reduced nitrogen and carbon. The C. difficile eut operon displays regulatory genetic elements and protein encoding regions in common with homologous loci found in the genomes of other bacteria, including the enteric pathogens Salmonella enterica and Enterococcus faecalis. The crystal structures of two microcompartment shell proteins, CD1908 and CD1918, and an uncharacterised protein with potential enzymatic activity, CD1925, were determined by X-ray crystallography. CD1908 and CD1918 display the same protein fold, though the order of secondary structure elements is permuted in CD1908 and this protein displays an N-terminal β-strand extension. These proteins form hexamers with molecules related by crystallographic and non-crystallographic symmetry. The structure of CD1925 has a cupin β-barrel fold and a putative active site that is distinct from the metal-ion dependent catalytic cupins. Thin-section transmission electron microscopy of Escherichia coli over-expressing eut proteins indicates that CD1918 is capable of self-association into arrays, suggesting an organisational role for CD1918 in the formation of this microcompartment. The work presented provides the basis for further study of the architecture and function of the C. difficile eut microcompartment, its role in metabolism and the wider consequences of intestinal colonisation and virulence in this pathogen.
Rao, Krishna; Safdar, Nasia
Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C. difficile infection (CDI) is increasing and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed. PMID:26344412
Cowardin, Carrie A; Petri, William A
Clostridium difficile is a Gram-positive, spore forming bacillus and the most common cause of antibiotic-associated diarrhea in the United States. Clinical outcomes of C. difficile infection (CDI) range from asymptomatic colonization to pseudomembranous colitis, sepsis and death. Disease is primarily mediated by the action of the Rho-glucosylating toxins A and B, which induce potent pro-inflammatory signaling within the host. The role of this inflammatory response during infection is just beginning to be appreciated, with recent data suggesting inflammatory markers correlate closely with disease severity. In addition to the toxins, multiple innate immune signaling pathways have been implicated in establishing an inflammatory response during infection. In intoxication-based models of disease, inflammation typically enhances pathogenesis, while protection from infection seems to require some level of inflammatory response. Thus, the host immune response plays a key role in shaping the course of infection and a balanced inflammatory response which eradicates infection without damaging host tissues is likely required for successful resolution of disease. PMID:25223264
Vickers, Richard J; Tillotson, Glenn; Goldstein, Ellie J C; Citron, Diane M; Garey, Kevin W; Wilcox, Mark H
Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI. PMID:27283730
Schoster, Angelika; Arroyo, Luis; Staempfli, Henry;
Clostridium difficile and Clostridium perfringens are important causes of equine colitis but can also be found in healthy individuals. Epidemiologic information is restricted to cross-sectional studies of fecal shedding with little information on prevalence in gastrointestinal compartments other...... than feces and variability in shedding over time. The objectives were to investigate the presence of C. difficile and C. perfringens in healthy horses over time and assess prevalence in different gastrointestinal compartments. Feces were collected monthly from 25 horses for one year. Ingesta were...... collected from nine GI compartments of a separate group of 15 euthanized horses. Selective enrichment culture was performed, followed by toxin gene detection and ribotyping (C. difficile) and multiplex PCR (C. perfringens). Toxigenic C. difficile was isolated from 15/275 (5.5%) samples from 10/25 (40...
Polage, Christopher R.; Gyorke, Clare E.; Kennedy, Michael A.; Leslie, Jhansi L.; Chin, David L.; Wang, Susan; Nguyen, Hien H.; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W.; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S.; Panacek, Edward A.; Goodell, Parker B.; Solnick, Jay V.; Cohen, Stuart H.
IMPORTANCE Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. OBJECTIVE To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI. DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. MAIN OUTCOMES AND MEASURES Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. RESULTS Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox−/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was
Full Text Available Rahul Pathak,1 Hill Ambrose Enuh,1 Anish Patel,1 Prasanna Wickremesinghe21Department of Internal Medicine, New York Medical College, Internal Medicine Program at Richmond University Medical Center, Staten Island, NY, USA; 2Department of Gastrointestinal Medicine, New York Medical College, Internal Medicine Program at Richmond University Medical Center, Staten Island, NY, USABackground: Clostridium difficile infection (CDI has become a global concern over the last decade. In the United States, CDI escalated in incidence from 1996 to 2005 from 31 to 64/100,000. In 2010, there were 500,000 cases of CDI with an estimated mortality up to 20,000 cases a year. The significance of this problem is evident from the hospital costs of over 3 billion dollars annually. Fecal microbiota transplant (FMT was first described in 1958 and since then about 500 cases have been published in literature in various small series and case reports. This procedure has been reported mainly from centers outside of the United States and acceptance of the practice has been difficult. Recently the US Food and Drug Administration (FDA labeled FMT as a biological drug; as a result, guidelines will soon be required to help establish it as a mainstream treatment. More US experience needs to be reported to popularize this procedure here and form guidelines.Method: We did a retrospective review of our series of patients with relapsing CDI who were treated with FMT over a 3-year period. We present our experience with FMT at a community hospital as a retrospective review and describe our procedure.Results: There were a total of 12 patients who underwent FMT for relapsing C. difficile. Only one patient failed to respond and required a second FMT. There were no complications associated with the transplant and all patients had resolution of symptoms within 48 hours of FMT.Conclusion: FMT is a cheap, easily available, effective therapy for recurrent CDI; it can be safely performed in a
Trubiano, Jason A; Gardiner, Bradley; Kwong, Jason C; Ward, Peter; Testro, Adam G; Charles, Patrick G P
We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option. PMID:23117471
Full Text Available PURPOSE: To look for the presence of intestinal brush border membrane (BBM enzymes in the faecal samples of patients with Clostridium difficile association. METHODS: One hundred faecal samples were investigated for C.difficile toxin (CDT. Simultaneous assays for faecal excretion of intestinal BBM enzymes viz., disaccharidases, alkaline phosphatase (AP and leucine aminopeptidase (LAP were also done. RESULTS: C.difficile toxin was detected in 25 (25% of the samples with a titre ranging from 10 to 160. No significant difference (p>0.05 was seen between the CDT positive and negative groups with any of the disaccharidases studied. However, significant increase (pC.difficile diarrhoea.
Carroll, Karen C; Buchan, Blake W; Tan, Sokha; Stamper, Paul D; Riebe, Katherine M; Pancholi, Preeti; Kelly, Cheryl; Rao, Arundhati; Fader, Robert; Cavagnolo, Robert; Watson, Wendy; Goering, Richard V; Trevino, Ernest A; Weissfeld, Alice S; Ledeboer, Nathan A
The Verigene Clostridium difficile Nucleic Acid test (Verigene CDF test) (Nanosphere, Northbrook, IL) is a multiplex qualitative PCR assay that utilizes a nanoparticle-based array hybridization method to detect C. difficile tcdA and tcdB in fecal specimens. In addition, the assay detects binary toxin gene sequences and the single base pair deletion at nucleotide 117 (Δ 117) in tcdC to provide a presumptive identification of the epidemic strain 027/NAP1/BI (referred to here as ribotype 027). This study compared the Verigene CDF test with anaerobic direct and enriched toxigenic culture on stool specimens from symptomatic patients among five geographically diverse laboratories within the United States. The Verigene CDF test was performed according to the manufacturer's instructions, and the reference methods performed by a central laboratory included direct culture onto cycloserine cefoxitin fructose agar (CCFA) and enriched culture using cycloserine cefoxitin mannitol broth with taurocholate and lysozyme. Recovered isolates were identified as C. difficile using gas liquid chromatography and were tested for toxin using a cell culture cytotoxicity neutralization assay. Strains belonging to ribotype 027 were determined by PCR ribotyping and bidirectional sequencing for Δ 117 in tcdC. A total of 1,875 specimens were evaluable. Of these, 275 specimens (14.7%) were culture positive by either direct or enriched culture methods. Compared to direct culture alone, the overall sensitivity, specificity, positive predictive value, and negative predictive value for the Verigene CDF test were 98.7%, 87.5%, 42%, and 99.9%, respectively. Compared to combined direct and enriched culture results, the sensitivity, specificity, positive predictive value, and negative predictive values of the Verigene CDF test were 90.9%, 92.5%, 67.6%, and 98.3%, respectively. Of the 250 concordantly culture-positive specimens, 59 (23.6%) were flagged as "hypervirulent"; 53 were confirmed as ribotype
Priscilla A. Johanesen
Full Text Available Clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. Central to predisposition to C. difficile infection is disruption of the gut microbiome by antibiotics. Being a Gram-positive anaerobe, C. difficile is intrinsically resistant to a number of antibiotics. Mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. While resistance to antibiotics currently used to treat C. difficile infection has not yet been detected, it may be only a matter of time before this occurs, as has been seen with other bacterial pathogens. This review will discuss C. difficile disease pathogenesis, the impact of antibiotic use on inducing disease susceptibility, and the role of antibiotic resistance and mobile elements in C. difficile epidemiology.
Dingle, Kate E; Griffiths, David; Didelot, Xavier; Evans, Jessica; Vaughan, Alison; Kachrimanidou, Melina; Stoesser, Nicole; Jolley, Keith A; Golubchik, Tanya; Harding, Rosalind M; Peto, Tim E; Fawley, Warren; Walker, A Sarah; Wilcox, Mark; Crook, Derrick W
Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings. The major virulence determinants are large clostridial toxins, toxin A (tcdA) and toxin B (tcdB), encoded within the pathogenicity locus (PaLoc). Isolates vary in pathogenicity from hypervirulent PCR-ribotypes 027 and 078 with high mortality, to benign non-toxigenic strains carried asymptomatically. The relative pathogenicity of most toxigenic genotypes is still unclear, but may be influenced by PaLoc genetic variant. This is the largest study of C. difficile molecular epidemiology performed to date, in which a representative collection of recent isolates (n = 1290) from patients with CDI in Oxfordshire, UK, was genotyped by multilocus sequence typing. The population structure was described using NeighborNet and ClonalFrame. Sequence variation within toxin B (tcdB) and its negative regulator (tcdC), was mapped onto the population structure. The 69 Sequence Types (ST) showed evidence for homologous recombination with an effect on genetic diversification four times lower than mutation. Five previously recognised genetic groups or clades persisted, designated 1 to 5, each having a strikingly congruent association with tcdB and tcdC variants. Hypervirulent ST-11 (078) was the only member of clade 5, which was divergent from the other four clades within the MLST loci. However, it was closely related to the other clades within the tcdB and tcdC loci. ST-11 (078) may represent a divergent formerly non-toxigenic strain that acquired the PaLoc (at least) by genetic recombination. This study focused on human clinical isolates collected from a single geographic location, to achieve a uniquely high density of sampling. It sets a baseline of MLST data for future comparative studies investigating genotype virulence potential (using clinical severity data for these isolates), possible reservoirs of human CDI, and the evolutionary origins of hypervirulent strains
Full Text Available Critically-ill patients constitute majority of the patients hospitalized in ICU wards (1, 2. This group of patients demands special considerations and measures of care (3-6. Clostridium difficile infection causes dangerous, painful and persistent diarrhea in critically ill patients. Its treatment consists of enteral metronidazol or vancomycin in combination with IV antibiotics cessation. Recently, probiotics have been considered as an alternative treatment for pseudomembranous colitis. In 1958, fecal microbial transplant was first described from healthy individuals to sick patients to displace pathogenic microbes from the intestine by re-establishing a healthy microbial community. Since then, it has gained value as “express stool treatment” or currently known as “fecal transplant”. Last year, FDA classified stool as drug, which typically requires an Investigational New Drug application (IND. However, in July 2013, the FDA issued guidance stating that it would exercise enforcement discretion for physicians administering FMT to treat patients with recurrent Clostridium difficile infection. Accordingly, considering stool as a tissue product or giving it its own classification, as FDA approved for blood, would keep patients safe, ensure broad access and facilitate research (7.It should be taken into consideration that some complications might accompany fecal microbial transplant such as making patients susceptible for conditions like obesity or autoimmune disorders.Safety and quality assurance starts from pre-enrollment donor screening, donor testing (17 serological and stool-based assays, donor monitoring and process control. The composition of the bacterial community has been shown to change when stored at -80oC compared to the samples stored at -20oC and it has been recommended to store the samples of intestinal content at -20oC before use for bacterial community analysis, instead of the current practice at -80oC (7, 8. However, if
Youssef D; Grant WB; Peiris AN
Dima Youssef,1 William B Grant,2 Alan N Peiris3,41Department of Internal Medicine, Division of Infectious Diseases, 2Sunlight, Nutrition and Health Research Center, San Francisco, CA USA; 3Department of Medicine, Mountain Home VAMC, 4Department of Medicine, East Tennessee State University, Johnson City, Tennessee, USAIn the July 3, 2012 issue of the journal of Risk Management and Healthcare Policy, Martinez et al present a nice review on Clostridium difficile (C. difficile) infections.1 The d...
Abrar K Thabit,1,2 David P Nicolau1,3 1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA; 2Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA Background: Clostridium difficile infection ranges from mild to severe prolonged diarrhea with systemic symptoms. Previous studies have assessed the correlation of some disease severity parameters to C. difficile ribotypes. Ho...
Song, Yang; Garg, Shashank; Girotra, Mohit; Maddox, Cynthia; von Rosenvinge, Erik C.; Dutta, Anand; Dutta, Sudhir; Fricke, W. Florian
Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health co...
Carlson, Paul E.; Kaiser, Alyssa M.; McColm, Sarah A.; Bauer, Jessica M.; Vincent B Young; Aronoff, David M.; Hanna, Philip C.
Over the past two decades, Clostridium difficile infections have been increasing in both number and severity throughout the world. As with other spore forming bacteria, germination is a vital step in the life cycle of this pathogen. Studies have examined differences in sporulation and toxin production among a number of C. difficile clinical isolates; however, few have examined differences in germination and the relationship between this phenotype and disease severity. Here, over 100 C. diffic...
Boyle, Nicole M.; Magaret, Amalia; Stednick, Zach; Morrison, Alex; Butler-Wu, Susan; Zerr, Danielle; Rogers, Karin; Podczervinski, Sara; Cheng, Anqi; Wald, Anna; Pergam, Steven A
Background Although hematopoietic cell transplant (HCT) recipients are routinely exposed to classic risk factors for Clostridium difficile infection (CDI), few studies have assessed CDI risk in these high-risk patients, and data are especially lacking for pediatric HCT recipients. We aimed to determine incidence and risk factors for CDI in adult and pediatric allogeneic HCT recipients. Methods CDI was defined as having diarrhea that tested positive for C. difficile via PCR, cytotoxin assay, o...
Arvand, Mardjan; Bettge-Weller, Gudrun
Clostridium difficile-isolates associated with CDI in different healthcare facilities in Hesse were analysed. The most common ribotypes were 001 (31.1%) and 027 (27.0%). The proportion of ribotype 027 among regional C. difficile-isolates was 10.8% in North Hesse, 17.2% in Middle Hesse, and 33.5% in the Rhine-Main Metropolitan Area. In the latter region, ribotype 027 was the most prevalent ribotype. PMID:27063988
Gupta A; Khanna S
Arjun Gupta, Sahil Khanna Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Abstract: There has been a startling shift in the epidemiology of Clostridium difficile infection over the last decade worldwide, and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile i...
Schoster, Angelika; Arroyo, Luis Guillermo; Staempfli, Henry Rolf;
BACKGROUND: Clostridium difficile and Clostridium perfringens are commonly associated with colitis in equids, but healthy carriers exist. Scarce information is available on the prevalence of Clostridium spp. in gastrointestinal compartments other than faeces in healthy horses, and it is unknown w...
Drudy, Denise; Harnedy, N.; Fanning, S; O’Mahony, R.; Kyne, L.
Clostridium difficile is a major cause of infectious diarrhoea in hospitalised patients. Most pathogenic C. difficile strains produce two toxins, A and B; however, clinically relevant toxin A-negative, toxin Bpositive (A– B+ ) strains of C. difficile that cause diarrhoea and colitis in humans have been isolated worldwide. The aims of this study were to isolate and characterise A– B+ strains from two university hospitals in Dublin, Ireland. Samples positive for C. difficile were identified dai...
Ali, Shanom; Muzslay, Monika; Wilson, Peter
The horizontal transmission of Clostridium difficile in the hospital environment is difficult to establish. Current methods to detect C. difficile spores on surfaces are not quantitative, lack sensitivity, and are protracted. We propose a novel rapid method to detect and quantify C. difficile contamination on surfaces. Sponge swabbing was compared to contact plate sampling to assess the in vitro recovery of C. difficile ribotype 027 contamination (∼100, 101, or 102 CFU of spores) from test su...
Norman, K N; Harvey, R B; Scott, H M; Hume, M E; Andrews, K; Brawley, A D
The objectives of this study were to compare the prevalence of Clostridium difficile (Cd) among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Results are based on 131 Cd isolates from 1008 swine fecal samples and pork trim samples (overall prevalence of 13%). The prevalence (number positive/number tested in production type) of Cd was different between the groups (Pgenes, 129 isolates harbored a 39 base pair deletion in the tcdC gene, 120 isolates were toxinotype V, and all 131 of the isolates were positive for the binary toxin gene cdtB. All isolates were resistant to cefoxitin, ciprofloxacin, and imipenem, whereas all were sensitive to metronidazole, piperacillin/tazobactam, amoxicillin/clavulanic acid, and vancomycin. The majority of isolates were resistant to clindamycin; resistant or intermediate to ampicillin; and sensitive to tetracycline and chloramphenicol. There was an increased (P=0.001) number of isolates for the timeframe of September to February compared to March to August. PMID:19778624
Arnold, A; Pope, C; Bray, S; Riley, P; Breathnach, A; Krishna, S; Planche, T
Commonly used immunoassays have limitations as stand-alone tests for the diagnosis of Clostridium difficile infection (CDI). In particular, the specificity of these assays means that these tests generate a relatively large number of false-positive results. We introduced a two-stage regimen for CDI as routine. Unformed stool samples received in our laboratory were initially tested with a Meridian Premier enzyme immunoassay (EIA) and positive samples were retested with reference testing methods (toxigenic culture and cell cytotoxicity assay). Clinicians received diagnostically useful information on the day that the sample arrived in the laboratory, with definitive negative and provisional positive results made available. We reviewed the first 3643 unformed stool specimens of which 158/3643 (4.3%) were provisionally positive by EIA. Of the 158 samples that were EIA positive, 119 were confirmed as being positive by at least one of the reference methods, giving a positive predictive value in this population of 75% (95% confidence interval: 67.6-81.7%). Comparison of the optical density values of the EIA lying between true and false-positive results suggests that the introduction of a second cut-off value would improve diagnostics. A test with two cut-offs would give the following results: 'positive', 'negative' and 'indeterminate result, please perform confirmatory test'. This algorithm was a simple and cost-effective method to immediately improve diagnostics, but there is an urgent need for further research in laboratory diagnosis for CDI. PMID:20638749
Full Text Available OBJECTIVE: Clostridium difficile infection (CDI is a major cause of morbidity and biomarkers that predict severity of illness are needed. Procalcitonin (PCT, a serum biomarker with specificity for bacterial infections, has been little studied in CDI. We hypothesized that PCT associated with CDI severity. DESIGN: Serum PCT levels were measured for 69 cases of CDI. Chart review was performed to evaluate the presence of severity markers and concurrent acute bacterial infection (CABI. We defined the binary variables clinical score as having fever (T >38°C, acute organ dysfunction (AOD, and/or WBC >15,000 cells/mm(3 and expanded score, which included the clinical score plus the following: ICU admission, no response to therapy, colectomy, and/or death. RESULTS: In univariate analysis log10 PCT associated with clinical score (OR 3.13, 95% CI 1.69-5.81, P0.2 ng/mL was 81% sensitive/73% specific for a positive clinical score and had a negative predictive value of 90%. CONCLUSION: An elevated PCT level associated with the presence of CDI severity markers and CDI was unlikely to be severe with a serum PCT level below 0.2 ng/mL. The extent to which PCT changes during CDI therapy or predicts recurrent CDI remains to be quantified.
Kola, Axel; Wiuff, Camilla; Akerlund, Thomas; van Benthem, Birgit H; Coignard, Bruno; Lyytikäinen, Outi; Weitzel-Kage, Doris; Suetens, Carl; Wilcox, Mark H; Kuijper, Ed J; Gastmeier, Petra
To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol. PMID:27469420
Varshney, Jyotika B; Very, Katherine J; Williams, Jen L; Hegarty, John P; Stewart, David B; Lumadue, Jeanne; Venkitanarayanan, Kumar; Jayarao, Bhushan M
A study was conducted to determine the prevalence of Clostridium difficile and characterize C. difficile isolates from human stool and retail grocery meat samples. Human stool samples (n=317) were obtained from a clinical laboratory and meat samples (n=303) were collected from 8 retail grocery stores from October 2011 through September 2012 from Centre County of Pennsylvania and were examined for C. difficile. C. difficile was isolated from 16.7% of stool samples (n=317) and 6.9%, 11.5%, 14.5%, and 7.8% of beef (n=72), pork (n=78), turkey (n=76), and chicken (n=77) samples, respectively. Six different toxin gene profiles were detected in all human and meat isolates of C. difficile based on the presence or absence of toxin genes tcdA, tcdB, and cdtA and cdtB. Interestingly, 75.6% of the human C. difficile isolates lacked any deletion in the tcdC gene (139-bp), whereas a 39-bp deletion was observed in 61.3% of the C. difficile strains isolated from meat samples. C. difficile from meat samples were more susceptible to clindamycin, moxifloxacin, vancomycin, and metronidazole than C. difficile isolates from human samples. Twenty-five different ribotypes were identified in human and meat C. difficile isolates. In conclusion, significant genotypic and phenotypic differences were observed between human and meat isolates of C. difficile; however, a few C. difficile isolates from meat-in particular ribotypes 078, PA01, PA05, PA16, and PA22 with unique profiles (toxin gene, tcdC gene size and antimicrobial resistance profiles)-were similar to human C. difficile isolates. PMID:25269079
Levett, P N
Stool specimens examined for the presence of Clostridium difficile and its cytotoxin were screened by gas liquid chromatography for the presence of volatile fatty acids and p-cresol. Twenty seven of 110 (25%) stools yielded C difficile or cytotoxin; iso-valeric acid was detected in 63/110 (57%) and iso-caproic acid in 18/110 (16%) stools. Para-cresol was found in 24/71 (34%) stools examined. Iso-valeric acid was detected in 85% of stools positive for C difficile, whereas iso-caproic acid (41%...
Carstensen, Jeppe West; Hansen, Axel Kornerup
Faecal transplantation as a treatment for Clostridium difficile infection, ulcerative colitis and the metabolic syndrome Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial......, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal...... transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection....
Daniela Zilio Larentis
Full Text Available Background. The epidemiology of Clostridium difficile infection has changed over time. Therefore, it is essential to monitor the characteristics of patients at risk of infection and factors associated with poor prognosis. Objective. To evaluate factors associated with C. difficile infection and with poor prognosis in those with documented C. difficile colitis. Methods. A retrospective case-control study of 75 patients with documented C. difficile colitis and 75 controls with hospital-acquired diarrhea of other causes. Stepwise multiple logistic regression was used to identify factors associated with C. difficile infection among patients with hospital-acquired diarrhea. Results. Previous antibiotic treatment (odds ratio (OR, 13.3; 95% confidence interval (CI, 1.40–126.90, abdominal distension (OR, 3.85; 95% CI, 1.35–10.98, and fecal leukocytes (OR, 8.79; 95% CI, 1.41–54.61 are considered as predictors of C. difficile colitis; anorexia was negatively associated with C. difficile infection (OR, 0.15; 95% CI, 0.03–0.66. Enteral tube feeding was independently associated with a composite outcome that included in-hospital mortality, intensive care unit admission, and treatment failure (OR, 3.75; 95%CI, 1.24–11.29. Conclusions. Previous antibiotic use and presence of fecal leukocytes in patients with hospital-acquired diarrhea are associated with C. difficile colitis and enteral tube support with complications associated with C. difficile colitis.
Hong, Namki; Kim, Jung Ho; Park, Se Hee; Kim, Sung Bae; Song, In Ji; Ann, Hea Won; Ahn, Jin Young; Kim, Sun Bean; Ku, Nam Su; Lee, Kyungwon; Yong, Dongeun; Kim, June Myung
The incidence of Clostridium difficile infection is increasing worldwide, and its severity and resulting mortality are also on the rise. Metronidazole and oral vancomycin remain the treatments of choice, but there are concerns about treatment failure and the appearance of resistant strains. Furthermore, antibiotic therapy results in recurrence rates of at least 20%. Fecal transplantation may be a feasible treatment option for recurrent C. difficile infection; moreover, it may be an early treatment option for severe C. difficile infection. We report a case of severe C. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode. This is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of C. difficile infection in Korea. PMID:27104013
Full Text Available We applied whole-genome sequencing to reconstruct the spatial and temporal dynamics underpinning the expansion of Clostridium difficile ribotype 027 in Germany. Based on re-sequencing of genomes from 57 clinical C. difficile isolates, which had been collected from hospitalized patients at 36 locations throughout Germany between 1990 and 2012, we demonstrate that C. difficile genomes have accumulated sequence variation sufficiently fast to document the pathogen's spread at a regional scale. We detected both previously described lineages of fluoroquinolone-resistant C. difficile ribotype 027, FQR1 and FQR2. Using Bayesian phylogeographic analyses, we show that fluoroquinolone-resistant C. difficile 027 was imported into Germany at least four times, that it had been widely disseminated across multiple federal states even before the first outbreak was noted in 2007, and that it has continued to spread since.
Full Text Available Clostridium difficile is a frequently identified cause of nosocomial gastrointestinal disease. It has been proved to be a causative agent in antibiotic-associated diarrhea, antibiotic-associated colitis, and pseudomembraneous colitis. This study was aimed to determine the prevalence of C.difficile- associated diarrhea in hospitalized patients with nosocomial diarrhea. The 942 hospitalized patients stool samples with nosocomial diarrhea were collected at three hospitals in Tehran from Dec 2002 to Feb 2004.All the stool samples were cultured and in 97 (prevalence: 10.9% samples grew C.difficile that 57 (prevalence: 6.1% isolates were toxigenic by cytotoxicity assay and so 57 patients had C.difficile- associated diarrhea. Results of statistical analysis showed significant difference between the rate of C.difficile associated diarrhea and the patients ages (P<0.05.
Fenger, R V; Linneberg, A; Tvede, M;
The incidence of Clostridium difficile-associated infections is increasing, but it remains to be defined whether any change in the seroprevalence of C. difficile has also occurred. In a population-based study of the general adult population, 734 subjects, aged 15-69 years, were examined on two...... occasions 8 years apart (1990 and 1998) for the presence of antibodies against C. difficile in serum. The overall seroprevalence of C. difficile increased significantly from 19% in 1990 to 27% in 1998 (P<0.0001). The seroprevalence increased with increasing age in both 1990 and 1998, but the increase was...... about four times higher in 1998 than in 1990. In conclusion, the observed increase in seroprevalence suggests a higher exposure to C. difficile in the general Danish adult population....
Janezic, Sandra; Zidaric, Valerija; Pardon, Bart;
Background: Clostridium difficile is an important cause of intestinal infections in some animal species and animals might be a reservoir for community associated human infections. Here we describe a collection of animal associated C. difficile strains from 12 countries based on inclusion criteria......; 10 countries). Conclusions: This results show that although PCR ribotype 078 is often reported as the major animal C. difficile type, especially in pigs, the variability of strains in pigs and other animal hosts is substantial. Most common human PCR ribotypes (014/020 and 002) are also among most...... prevalent animal associated C. difficile strains worldwide. The widespread dissemination of toxigenic C. difficile and the considerable overlap in strain distribution between species furthers concerns about interspecies, including zoonotic, transmission of this critically important pathogen....
Rodrigo Otávio Silveira Silva
Full Text Available In spite of the substantial role of Clostridium difficile in causing diarrhea in piglets, there have been few reports of the disease caused by this bacterium in Rio Grande do Sul, Brazil. In this paper, we describe an outbreak of C. difficile-associated diarrhea in a pig farm in Brazil. The diarrhea rate increased in piglets 1-to-7 days old from an average of 2% to approximately 20%. Necropsied piglets showed mesocolon edema, and in a histological evaluation, severe necrotizing neutrophilic colitis was observed. The intestinal contents were positive for the A/B toxins of C. difficile and negative for other tested enteropathogens. The association between the clinical signs, post mortem findings and laboratory exams confirmed the diagnosis of C. difficile-associated diarrhea. The present report confirms C. difficile as a pathogen in swine in Brazil and highlights the need for up to date routine laboratory protocols for the diagnosis of this disease in swine.
Schubert, Alyxandria M.; Rogers, Mary A M; Ring, Cathrin; Mogle, Jill; Petrosino, Joseph P.; Young, Vincent B.; Aronoff, David M.; Schloss, Patrick D.
ABSTRACT Antibiotic usage is the most commonly cited risk factor for hospital-acquired Clostridium difficile infections (CDI). The increased risk is due to disruption of the indigenous microbiome and a subsequent decrease in colonization resistance by the perturbed bacterial community; however, the specific changes in the microbiome that lead to increased risk are poorly understood. We developed statistical models that incorporated microbiome data with clinical and demographic data to better ...
Liu, Ji; Ma, Yi; Sun, Chun-Li; Li, Shan; Wang, Ju-Fang
High Mobility Group Box1 (HMGB1), a damage-associated inflammatory factor, plays an important role in the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, the role of the HMGB1 in TcdA-induced ER stress was identified. Clostridium difficile toxin A is one of the major virulence factors of C. difficile infection (CDI) and has been proved to induce apoptotic cell death through ER stress. Our results showed that HMGB1 might play an important role in the TcdA-induced ER stress and unfolded protein response. HMGB1 activated molecular markers and induced the C/EBP homologous protein upregulation (CHOP). This study may provide the essential information for better understanding of the molecular mechanisms involved in CDI. PMID:27579314
Tae, Chung Hyun; Jung, Sung-Ae; Song, Hyun Joo; Kim, Seong-Eun; Choi, Hee Jung; Lee, Miae; Hwang, Yusun; Kim, Heejung; Lee, Kyungwon
Clostridium difficile (C. difficile) is a common causative agent of pseudomembranous colitis (PMC). C. difficile-associated diarrhea (CDAD) ranges from mild diarrhea to life threatening PMC. Recently, a highly virulent strain of C. difficile polymerase chain reaction ribotype 027 was found in North America, Europe, and Japan. A 52-yr-old woman with anti-tuberculosis medication and neurogenic bladder due to traffic accident experienced five episodes of C. difficile PMC after taking antibiotics for pneumonia along with septic shock and acute renal failure. She was readmitted to the intensive care unit and treated with oral vancomycin with refractory of oral metronidazole, inotropics and probiotics for over 60 days. C. difficile isolated both at the first and the last admission was identified as C. difficile ribotype 027 by ribotyping, toxinotyping, and tcdC gene sequencing, which turned out the same pathogen as the epidemic hypervirulent B1/NAP1 strain. This is the first case of C. difficile PCR ribotype 027 in Korea. After discharge, she was maintained on probiotics and rifaximin for 3 weeks. She had no relapse for 6 months. PMID:19543521
Patrick Basu, P.; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N. V.; Mohan, Vinod
Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5–10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings. PMID:21180604
Ebrahim; Rahimi; Zahra; Sadat; Afzali; Zcinab; Torki; Baghbadorani
Objective:To determine the prevalence and antimicrobial resistance of Clostridium difficile(C.difficile) isolated from ready-to-eat foods of Iran.Methods:From January to August 2013,a total of 368 unpacked ieady-to-eat food samples were purchased from randomly selected supermarkets,retail stores and restaurants located in Isfahan and Shahrekord,Iran and were evaluated for the presence of C.difficile.Results:C.difficile spores were detected in 5(1.36%) of the 368 samples.The highest prevalence of C.difficile was found in fasl salad(4.29%).followed by yogurt stew(2%),and olovyeh salad(0.93%).All 140 maccaroni salad and I’alafel sandwich samples were negative for C.difficile.One of the five C.difficile isolates(20%) contained tcdA,tcdB and cdtB toxin genes and four strains(80%) contained tcdA.and tcdB toxin genes.Also,among the five C.difficile isolates,only three strains were found to be toxigenic for toxin A and/or B by ELISA.Isolates were susceptible to vancomycin and metronidazole,but variably resistant to other antimicrobial drugs.Conclusions:This study,combined with studies on other food sources,suggests that widespread contamination of food is common.
Full Text Available The prevalence of Clostridium difficile infection and the associated burden have recently increased in many countries. While the main risk factors for C. difficile infection include old age and antibiotic use, the prevalence of this infection is increasing in low-risk groups. These trends highlight the need for research on C. difficile infection. This study pointed out the prevalence and economic burden of C. difficile infection and uses the representative national data which is primarily from the database of the Korean Health Insurance Review and Assessment Service, for 2008–2011. The annual economic cost was measured using a prevalence approach, which sums the costs incurred to treat C. difficile infection. C. difficile infection prevalence was estimated to have increased from 1.43 per 100,000 in 2008 to 5.06 per 100,000 in 2011. Moreover, mortality increased from 69 cases in 2008 to 172 in 2011. The economic cost increased concurrently, from $2.4 million in 2008 to $7.6 million, $10.5 million, and $15.8 million in 2009, 2010, and 2011, respectively. The increasing economic burden of C. difficile infection over the course of the study period emphasizes the need for intervention to minimize the burden of a preventable illness like C. difficile infection.
Bandelj, Petra; Blagus, Rok; Briski, France; Frlic, Olga; Vergles Rataj, Aleksandra; Rupnik, Maja; Ocepek, Matjaz; Vengust, Modest
Farm animals have been suggested to play an important role in the epidemiology of Clostridium difficile infection (CDI) in the community. The purpose of this study was to evaluate risk factors associated with C. difficile dissemination in family dairy farms, which are the most common farming model in the European Union. Environmental samples and fecal samples from cows and calves were collected repeatedly over a 1 year period on 20 mid-size family dairy farms. Clostridium difficile was detected in cattle feces on all farms using qPCR. The average prevalence between farms was 10% (0-44.4%) and 35.7% (3.7-66.7%) in cows and calves, respectively. Bacterial culture yielded 103 C. difficile isolates from cattle and 61 from the environment. Most C. difficile isolates were PCR-ribotype 033. A univariate mixed effect model analysis of risk factors associated dietary changes with increasing C. difficile prevalence in cows (P = 0.0004); and dietary changes (P = 0.004), breeding Simmental cattle (P = 0.001), mastitis (P = 0.003) and antibiotic treatment (P = 0.003) in calves. Multivariate analysis of risk factors found that dietary changes in cows (P = 0.0001) and calves (P = 0.002) increase C. difficile prevalence; mastitis was identified as a risk factor in calves (P = 0.001). This study shows that C. difficile is common on dairy farms and that shedding is more influenced by farm management than environmental factors. Based on molecular typing of C. difficile isolates, it could also be concluded that family dairy farms are currently not contributing to increased CDI incidence. PMID:26968527
Floods can contaminate potable water and other resources, thus increasing the potential for fecal-oral transmission of pathogens. Clostridium difficile is a bacterium that can spread by water and cause acute gastrointestinal illness. It often affects older adults who are hospital...
Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A
Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID:26864803
McMullen, Kathleen M; Zack, Jeanne; Coopersmith, Craig M; Kollef, Marin; Dubberke, Erik; Warren, David K
An increased rate of Clostridium difficile-associated diarrhea (CDAD) was noted in 2 intensive care units of a university-affiliated tertiary care facility. One unit instituted enhanced environmental cleaning with a hypochlorite solution in all rooms, whereas the other unit used hypochlorite solution only in rooms of patients with CDAD. The CDAD rates decreased in both units. PMID:17265404
Zidaric, V.; Janezic, S.; Indra, A.;
Clostridium difficile is an anaerobic sporogenic bacterium traditionally associated with human nosocomial infections, and animals have been recognized as an important potential reservoir for human infections (Rodriguez-Palacios et al., 2013). Ribotype 078 is often reported in animals but according...
Aarestrup, Frank Møller; Tvede, Michael
A total of 65 toxigenic Clostridium difficile strains isolated from patients with antibiotic-associated diarrhea were tested for susceptibility to avilamycin, flavomycin, monensin, and salinomycin. Except for flavomycin the substances showed in vitro efficacy comparable to reports of the currently...
... Use ©2016 UpToDate, Inc. Patient education: Antibiotic-associated diarrhea caused by Clostridium difficile (Beyond the Basics) Authors ... last updated: Jun 15, 2015. OVERVIEW — Antibiotic-associated diarrhea refers to diarrhea that develops in a person ...
Bacci, S; St-Martin, G; Olesen, B;
We report an outbreak of Clostridium difficile PCR ribotype 027 in Denmark. The outbreak includes to date 73 cases from the area north of Copenhagen, but there may be related cases elsewhere in Zealand. Most infections are healthcare-associated and in patients who previously received antibiotic...
Fløe, Andreas; Leutscher, Peter
Treatment of severe Clostridium difficile infection (CDI) poses a clinical challenge. Emerging evidence supports the use of faecal microbiota transplantation (FMT). An 81-year-old man was admitted with a third recurrent episode of CDI within two months. Because of clinical deterioration with...
Naohiro Okano; Kentaro Iwata
Bron et al presented a retrospective study regarding the prophylactic use of antibiotics for variceal hemorrhage. Antibiotics appeared to improve the survival rate of patients without increasing clostridium difficile infection (CDI). We argue against the conclusion of the authors and consider that this result may be simply due to concurrent use of metronidazole, a therapeutic agent against CDI.
M. Hell (M.); C. Bernhofer (C.); P. Stalzer (P.); J.M. Kern (J.); H.J.H.M. Claassen (Eric)
textabstractIn the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains o
Wilden, Gwendolyn Mariëtta
This thesis is a combination of traumatic and non-traumatic events in the abdomen, and the optimization of treatment in both entities. The first part describes the very prevalent infection caused by the bacterium Clostridium difficile. The colitis caused by this infection can be severe and complicat
Postma, N.; Kiers, D.; Pickkers, P.
The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected
Søes, Lillian M; Brock, Inger; Torpdahl, Mia;
Increasing rates of Clostridium difficile-associated diarrhoea (CDAD) with an unusual, severe course have been reported in Canada, USA and several European countries since 2003. A new virulent strain, PCR ribotype 027 (CD027), is associated with this increase. We report the first Danish case of...