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antibiotic prophylaxis and the risk of clostridium difficile-associated diarrhoea.to test the hypothesis that extended antibiotic prophylaxis increases the risk of clostridium difficile -associated diarrhoea (cdad), we conducted a retrospective cohort study of 2641 patients under-going cardiovascular surgery. main outcome measures were the duration of prophylaxis (< 48 h vs. > 48 h) and the occurrence of cdad. cdad occurred in 31 patients (1.2%), who were significantly older (70 +/- 9 y vs. 66 +/- 10 y; p = 0.03), received more therapeutic antibiotics (2.2 +/- 1.9 vs. 0.4 +/- ...200111428874
variant toxin b and a functional toxin a produced by clostridium difficile c34.a particular property of clostridium difficile strain c34 is an insertion of approximately 2 kb in the tcda-c34 gene that does not hinder expression of a fully active tcda-c34 molecule. intoxication with tcda-c34 induced an arborized appearance in eukaryotic cells (d-type cytopathic effect); intoxication with tcdb-c34 induced a spindle-like appearance of cells (s-type cytopathic effect). inactivation of gtpases with purified toxins revealed that rho, rac, cdc42, and rap are substrates of tcda-c3 ...200111430410
pseudomembranous colitis after eradication of helicobacter pylori infection with a triple therapy.background: h.pylori (h.p.) infection of the gastric mucosa is causally related to chronic gastritis, peptic ulcer disease, malt-lymphoma and gastric cancer. there is also an evidence for a link between the h.p.-infection and non-ulcer dyspepsia and even extragastric diseases. the number of patients treated against h.p. infection is expanding. although in the last years the ppi-based triple therapies have been considered to be effective and safe, in some patients, however, severe side-effects ma ...200111433206
[diarrhea due to clostridium difficile toxin in hemato-oncological patients].in two patients with multiple myeloma, men aged 72 and 54 years, diarrhoea developed upon chemotherapy with vincristin, doxorubicin and dexamethasone (vad). in the second patient, diarrhoea developed after subsequent peripheral stem cell mobilisation. pseudomembranous colitis was seen in the first patient during endoscopy but an enzyme immunoassay of the faeces was false negative for clostridium difficile enterotoxin. the bacterium was later cultured from stool samples and toxins were detected i ...200111433658
"second-look" cytotoxicity: an evaluation of culture plus cytotoxin assay of clostridium difficile isolates in the laboratory diagnosis of cdad.clostridium difficile is one of the most frequent causes of hospital-acquired diarrhoea. our objective was to prove that some stool samples with a direct negative cytotoxicity assay may indeed harbour toxigenic c. difficile and that this can be demonstrated by performing a "second-look" cytotoxicity assay using the isolated c. difficile strains. over an eight-year period (1992-1999), the 8241 stool samples submitted for direct cell culture from patients with suspected c. difficile-associated dia ...200111439012
bacterial contamination of uniforms.microbiological sampling of nurses' uniforms was undertaken using a casella slit sampler. staphylococcus aureus, clostridium difficile and vancomycin-resistant enterococci were detected on uniforms both before and after a span of duty. recommendations for provision and changing of nurses' uniforms are made.200111439013
clostridium difficile-associated diarrhea and colitis.clostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea and colitis, typically after the use of broad-spectrum antibiotics. the clinical presentation ranges from self-limited diarrhea to fulminant colitis and toxic megacolon. the incidence of this disease is increasing, resulting in major medical and economic consequences. although most cases respond quickly to medical treatment, c difficile colitis may be serious, especially if diagnosis and treatment are delayed. recu ...200111444405
evidence for holin function of tcde gene in the pathogenicity of clostridium difficile.toxigenic strains of clostridium difficile produce two large bacterial toxins called toxins a (tcda) and b (tcdb). tcda and tcdb genes are located on the pathogenicity locus of c. difficile, a unique characteristic of toxigenic strains of this species. intergenic to the two toxin genes is tcde, a small 501-bp open reading frame of unknown function. expression of the tcde gene in escherichia coli caused bacterial cell death. computational analysis of the amino acid sequence of tcde revealed struc ...200111444771
deletion of neutral endopeptidase exacerbates intestinal inflammation induced by clostridium difficile toxin a.toxin a (txa) of clostridium difficile induces acute inflammation of the intestine initiated by release of substance p (sp) and activation of the neurokinin-1 receptor. however, the mechanisms that terminate this response are unknown. we determined whether the sp-degrading enzyme neutral endopeptidase (nep, ec 3.4.24.11) terminates txa-induced enteritis. we used both genetic deletion and pharmacological inhibition of nep to test this hypothesis. in wild-type mice, instillation of txa (0.5-5 micr ...200111447035
activity of bms284756 (t-3811) tested against anaerobic bacteria, campylobacter jejuni, helicobacter pylori and legionella spp.bms284756, a novel des-fluoro (6) quinolone (formerly t-3811), was tested for activity and spectrum using reference agar dilution (ad) and etest (ab biodisk, solna, sweden) methods. the antimicrobial activities of bms284756, ciprofloxacin, gatifloxacin, levofloxacin, and trovafloxacin were evaluated against campylobacter jejuni (38 strains), helicobacter pylori (21 strains), legionella spp. (66 strains), and 197 anaerobic isolates. bms284756 (mic(90), 0.008 microg/ml) was four-fold more active t ...200111448563
probiotics: "living drugs".the uses, mechanisms of action, and safety of probiotics are discussed. probiotics are live microorganisms or microbial mixtures administered to improve the patient's microbial balance, particularly the environment of the gastrointestinal tract and the vagina. the yeast saccharomyces boulardii and the bacterium lactobacillus rhamnosus, strain gg, have shown efficacy in clinical trials for the prevention of antimicrobial-associated diarrhea. other probiotics that have demonstrated at least some p ...200111449853
gt160-246, a toxin binding polymer for treatment of clostridium difficile colitis.gt160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro and in vivo for neutralization of clostridium difficile toxin a and b activities. five milligrams of gt160-246 per ml neutralized toxin-mediated inhibition of protein synthesis in vero cells induced by 5 ng of toxin a per ml or 1.25 ng of toxin b per ml. in ligated rat ileal loops, 1 mg of gt160-246 neutralized fluid accumulation caused by 5 microg of toxin a. at doses as high as 80 mg/loop, cholestyramine provided i ...200111451694
resistance to moxifloxacin in toxigenic clostridium difficile isolates is associated with mutations in gyra.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 th ...200111451695
the effect of tumour necrosis factor (tnf) inhibitors in clostridium difficile toxin-induced paw oedema and neutrophil migration.clostridium difficile produces a potent enterotoxin and a cytotoxin, toxin a and toxin b, respectively. these toxins are associated with pseudomembranous colitis and antibiotic-associated diarrhoea. in the present study, we investigated the oedematogenic activity of both toxins, characterizing the time-course and dose-response of this pro-inflammatory event. we also explored the effects of two inhibitors of tumour necrosis factor (tnf) production, thalidomide and pentoxifylline, in neutrophil re ...200111453371
serum antibody responses to clostridium difficile toxin a: predictive and protective? 200111454789
regulation by rho family gtpases of il-1 receptor induced signaling: c3-like chimeric toxin and clostridium difficile toxin b inhibit signaling pathways involved in il-2 gene expression.in this study the participation of rho family gtpases in the regulation of il-1-activated protein kinase cascades controlling il-2 synthesis was investigated in murine el-4 thymoma cells. the recombinant c3-like chimeric toxin, which consists of the c3 toxin of clostridium limosum and the n-terminal part of clostridium botulinum c2 toxin (c2in-c3) interacting with the c2ii binding subunit to facilitate uptake into cells, and selectively inactivates rho a by adp-ribosylation, prevented il-1-stimu ...200111465119
the roles of clostridium difficile and enterotoxigenic clostridium perfringens in diarrhea in dogs.in this prospective study, feces of dogs with diarrhea were compared with feces of normal dogs for the presence of clostridium difficile, c difficile toxins a and b, c perfringens, and c perfingens enterotoxin (cpe). c difficile toxins a, b, or both were present in feces of 18 of 87 (21%) dogs with diarrhea and 4 of 55 (7%) normal dogs (p = 0.03), whereas cpe was present in the feces of 24 of 87 (28%) dogs with diarrhea and 3 of 55 (5%) normal dogs (p = 0.01). c difficile was isolated from 2 of ...200111467596
molecular epidemiology of endemic clostridium difficile infection.this is the first study to provide a comprehensive insight into the molecular epidemiology of endemic clostridium difficile and particularly that associated with a recently recognized epidemic strain. we dna fingerprinted all c. difficile isolates from the stools of patients with symptomatic antibiotic-associated diarrhoea and from repeated samples of the inanimate ward environment on two elderly medicine hospital wards over a 22-month period. notably, c. difficile was not recoverable from eithe ...200111467790
ischemic colitis associated with paclitaxel.systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. this report describes the case of a 49-year-old woman with liver metastases from a neuroendocrine tumor of unknown origin who developed mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. the patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea, which ...200111468447
culturing of stool samples from hospital inpatients. 200111469241
culturing of stool samples from hospital inpatients. 200111469243
patients' dying wishes. 200111469248
a prospective study of the roles of clostridium difficile and enterotoxigenic clostridium perfringens in equine diarrhoea.faecal samples from adult horses and from foals with diarrhoea or with normal faeces were evaluated for the presence of clostridium difficile, c. difficile toxins, c. perfringens enterotoxin (cpe) and c. perfringens spore counts. clostridium difficile was isolated from 7/55 horses (12.7%) and 11/31 foals (35.5%) with colitis, but from 1/255 normal adults (0.4%) and 0/47 normal foals (p<0.001). clostridium difficile toxins a and/or b were detected in 12/55 diarrhoeic adults (21.8%) and 5/30 diarr ...200111469775
optimum use of the microbiology laboratory in testing for stool pathogens and antimicrobial susceptibility testing (amst). 200111471325
evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of clostridium difficile-associated diarrhea.clostridium difficile is the principal pathogen associated with hospital-acquired acute diarrheal disease. we have evaluated the performances of six approaches for diagnosis of c. difficile-associated diarrhea (cdad). consecutive stool specimens (n = 200) from 133 patients were examined by cytotoxin assay, by culture of c. difficile on cycloserine-cefoxitin-fructose agar, and by toxin detection using four rapid immunoassay systems (oxoid toxin a test, immunocard toxin a test, techlab tox a/b ii ...200111474001
role of inducible cyclooxygenase and prostaglandins in clostridium difficile toxin a-induced secretion and inflammation in an animal model.cyclooxygenase (cox)-2 expression and inhibition were investigated in a rabbit ileal loop model of clostridium difficile colitis and diarrhea. intestinal tissue stimulated with c. difficile toxin a showed up-regulation of cox-2 expression in lamina propria macrophages and elevated prostaglandin levels. toxin a-stimulated loops exhibited severe inflammation and increased secretory volume. celecoxib, a specific cox-2 inhibitor, significantly reduced toxin a-induced prostaglandin production. furthe ...200111474431
the uptake and degradation of matrix-bound lipoproteins by macrophages require an intact actin cytoskeleton, rho family gtpases, and myosin atpase activity.a key cellular event in atherogenesis is the interaction of macrophages with lipoproteins in the subendothelium. in vivo, these lipoproteins are bound to matrix and often aggregated, yet most cell-culture experiments explore these events using soluble monomeric lipoproteins. we hypothesized that the internalization and degradation of matrix-retained and aggregated low density lipoprotein (ldl) by macrophages may involve the actin-myosin cytoskeleton in a manner that distinguishes this process fr ...200111477084
colonisation and transmission of clostridium difficile in healthy individuals examined by pcr ribotyping and pulsed-field gel electrophoresis.healthy adults who had not been exposed to antimicrobial agents for the preceding 4 weeks were examined for intestinal carriage of clostridium difficile. the 1234 individuals examined were composed of seven groups: three classes of university students, hospital workers at two hospitals, employees of a company and self-defence force personnel at a local station. overall, 94 (7.6%) individuals were positive for c. difficile by faecal culture but carriage rates among the study groups ranged from 4. ...200111478676
[clostridium difficile diarrhea: frequency of detection in a medical center in buenos aires, argentina].clostridium difficile has been recognized as the most important enteric pathogen of nosocomial antibiotic-associated diarrhea (cdad) in adults from industrialized countries. the importance of c. difficile as a cause of diarrhea in ambulatory patients appears underestimated or under-recognized. since the 1980's, outbreaks of cdad have been increasingly reported, but there are few data available in argentina. we developed a retrospective study to provide some information about cdad in our country. ...200111494752
isolation of clostridium innocuum from cases of recurrent diarrhea in patients with prior clostridium difficile associated diarrhea.clostridium innocuum isolates resistant to vancomycin (mic values of 16-24 microg/ml) were isolated from three patients with recurrent clostridium difficile -associated diarrhea (cdad). we discuss the clinical significance and problems associated with the identification and differentiation of these two clostridial species, which may result in misdiagnosis of patients.200111502376
fatal clostridium difficile infection of the small bowel after complex colorectal surgery. 200111504300
an essential role for rac/cdc42 gtpases in cerebellar granule neuron survival.rho family gtpases are critical molecular switches that regulate the actin cytoskeleton and cell function. in the current study, we investigated the involvement of rho gtpases in regulating neuronal survival using primary cerebellar granule neurons. clostridium difficile toxin b, a specific inhibitor of rho, rac, and cdc42, induced apoptosis of granule neurons characterized by c-jun phosphorylation, caspase-3 activation, and nuclear condensation. serum and depolarization-dependent survival signa ...200111509562
[diagnosis of clostridium difficile diarrhea: in search of a more efficient clinical focus].the clinical parameters for the suspicion of clostridium difficile infections, namely the use of antimicrobials and diarrhea, have a low predictive value for the diagnosis.200111510201
clostridium difficile infection in patients with neutropenia.clostridium difficile is the most important cause of nosocomial infectious diarrhea. the importance of c. difficile-associated diarrhea (cdad) has been poorly investigated in patients with neutropenia who have hematologic malignancies. a retrospective chart review of all patients treated in the leukemia ward of a university medical center during 1991-2000 determined that 875 courses of myelosuppressive chemotherapy were administered. cdad occurred in 7.0% of all cycles. in 8.2% of the patients, ...200111512083
fatal chemotherapy associated clostridium difficile infection--a case report.clostridium difficile associated diarrhoea or pseudomembranous colitis occasionally occurs without prior antibiotic usage. while the association of chemotherapy and clostridium difficile infection has previously been well recorded, the true incidence is unknown. we report a case of clostridium difficile associated diarrhoea after chemotherapy for lung cancer. the fatal outcome in this case and the increasing use of chemotherapy in this country highlights the need to have a high index of suspicio ...200111513059
the capsaicin vr1 receptor mediates substance p release in toxin a-induced enteritis in rats.the mechanism by which clostridium difficile toxin a causes substance p (sp) release and subsequent inflammation in the rat ileum is unknown. pretreatment with the vanilloid receptor subtype 1 (vr1) antagonist, capsazepine, before toxin a administration significantly inhibited toxin a-induced sp release and intestinal inflammation. intraluminal administration of the vr1 agonist capsaicin caused intestinal inflammation similar to the effects of toxin a. pretreatment with capsazepine before capsai ...200111514026
establishment of specific pathogen-free (spf) rat colonies using gnotobiotic techniques.gnotobiotic wistar rats were produced using gnotobiotic techniques, which were established in the production of a spf mouse colony, in order to establish a barrier-sustained colony. one strain of escherichia coli, 28 strains of bacteriodaceae (b-strains), three strains of lactobacillus (l-strains) and a chloroform-treated fecal suspension (chf, clostridium mixture) were prepared from conventional wistar rats as the microflora source. two groups of limited-flora rats, e. coli plus b-strains and e ...200111515091
persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation.epithelial secretion may play an important role in reducing bacterial colonization and translocation in intestine. if so, secretory dysfunction could result in increased susceptibility to infection and inflammation. we investigated whether long-term colonic secretory dysfunction occurs after a bout of colitis and if this is accompanied by an increase in bacterial colonization and translocation. rats were studied 6 wk after induction of colitis with trinitrobenzene sulfonic acid when inflammation ...200111518675
expression of connective tissue growth factor in human renal fibroblasts: regulatory roles of rhoa and camp.the induction of connective tissue growth factor (ctgf) was investigated in a human renal fibroblast cell line that exhibited many characteristics of primary human renal fibroblasts. induction of ctgf mrna was observed after treatment of the cells with transforming growth factor-beta (tgf-beta) or, even more prominently, lysophosphatidic acid (lpa). lpa induced a rapid transient increase in ctgf mrna expression, with maximal levels being observed after 1 to 2 h. this increase was accompanied by ...200111518778
the accordion sign at ct: report of a case of crohn's disease with diffuse colonic involvement.the accordion sign is a finding that could be seen on ct scans of the abdomen in patients who have received oral contrast material. initially, it was described as a sign specific of clostridium difficile colitis, but it is also reported to represent a sign of diffuse colonic edema of several other etiologies. we report a case of a patient with crohn's pancolitis whose abdominal ct scan presented the accordion sign throughout the entire large bowel together with signs of crohn's disease of the sm ...200111519553
life-threatening clostridium difficile-associated diarrhea induced by paclitaxel-carboplatin combination chemotherapy. 200111531624
intravenous metronidazole for the treatment of clostridium difficile colitis.severe clostridium difficile colitis may produce abdominal distention and ileus, precluding oral antibiotic therapy. stimulated by several case reports in which intravenous metronidazole was used, we reviewed our experience.200111535859
insulin-stimulated glut4 translocation in adipocytes is dependent upon cortical actin remodeling.rhodamine-labeled phalloidin staining of morphologically differentiated 3t3l1 adipocytes demonstrated that f-actin predominantly exists juxtaposed to and lining the inner face of the plasma membrane (cortical actin) with a smaller amount of stress fiber and/or ruffling actin confined to the cell bottom in contact with the substratum. the extent of cortical actin disruption with various doses of either latrunculin b or clostridium difficile toxin b (a rho family small gtp-binding protein toxin) d ...200111546823
variation in the surface layer proteins of clostridium difficile.surface layers (s-layers) form regular crystalline structures on the outermost surface of many bacteria. clostridium difficile possesses such an s-layer consisting of two protein subunits. treatment of whole cells of c. difficile with 5 m guanidine hydrochloride revealed two major proteins of different molecular masses characteristic of the s-layer on sds-page. in this study 25 isolates were investigated. a high degree of variability in the molecular mass of the two s-layer proteins was evident. ...200111549420
a comparison of side effects of levofloxacin to other agents concerning the ecological and microbiological effects on normal human flora.the safety of levofloxacin was compared to that of non-fluoroquinolone alternatives used for respiratory tract infections. results from five randomised controlled trials revealed that the incidence of any adverse events possibly associated with levofloxacin ranged from 5.8% to 22.7%, whereas that of comparators (ceftriaxone, cefuroxime axetil, clarithromycin and amoxicillin-clavulanic acid) ranged from 8.5% to 39.3%. the rate of adverse drug reactions (adrs) was lower for levofloxacin in all tri ...200111549785
influence of anti-helicobacter triple-therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora.proton pump inhibitor-based therapy including two antibiotics is the treatment of choice for helicobacter pylori infection. oral antibiotic treatment can lead to intestinal overgrowth of potentially pathogenic bacteria.200111552917
characterization of the enzymatic component of the adp-ribosyltransferase toxin cdta from clostridium difficile.certain strains of clostridium difficile produce the adp-ribosyltransferase cdt, which is a binary actin adp-ribosylating toxin. the toxin consists of the binding component cdtb, which mediates receptor binding and cellular uptake, and the enzyme component cdta. here we studied the enzyme component (cdta) of the toxin using the binding component of clostridium perfringens iota toxin (ib), which is interchangeable with cdtb as a transport component. ib was used because cdtb was not expressed as a ...200111553537
lack of effect of lactobacillus gg on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.to assess the efficacy of lactobacillus gg in preventing antibiotic-associated diarrhea (aad) in adults and, secondarily, to assess the effect of coadministered lactobacillus gg on the number of tests performed to determine the cause of diarrhea.200111560298
fatal pseudomembranous colitis associated with a variant clostridium difficile strain not detected by toxin a immunoassay.many clinical laboratories use toxin a immunoassays to test for clostridium difficile.200111560456
necrotizing fasciitis: a case of clostridial myonecrosis. 200111579903
the problem with cephalosporins.the cephalosporin antibiotics have become a major part of the antibiotic formulary for hospitals in affluent countries. they are prescribed for a wide variety of infections every day. their undoubted popularity relies upon lesser allergenic and toxicity risks as well as a broad spectrum of activity. it is the latter feature, however, that encourages the selection of microorganisms that are resistant to these agents. there are long-term implications for the treatment and control of this heterogen ...200111581224
clostridium difficile.clostridium difficile is a major cause of antibiotic-associated diarrhea and colitis. the incidence of infection with this organism is increasing in hospitals worldwide, consequent to the widespread use of broad-spectrum antibiotics. pathogenic strains of c. difficile produce two protein exotoxins, toxin a and toxin b, that cause colonic mucosal injury and inflammation. many patients who are colonized are asymptomatic, and recent evidence indicates that diarrhea and colitis occur in those indivi ...200111586556
the role of antibiotics in the treatment of infectious diarrhea.infectious diarrhea is a significant cause of morbidity and mortality and a common complaint in clinical practice. routine empirical use of antibiotics for infectious diarrhea should be avoided because of the self-limited nature of most cases, the cost of antibiotics, and the potential to worsen the already significant problem of antibiotic resistance of enteric pathogens. for patients with severe invasive or prolonged diarrhea or who are at high risk of complications, such as the elderly, diabe ...200111586559
epidemiology of clostridium difficile-associated infections.clostridium difficile is responsible for 15-25% of cases of antibiotic-associated diarrhea (aad) and for virtually all cases of antibiotic-associated pseudomembranous colitis (pmc). this anaerobic bacterium has been identified as the leading cause of nosocomial infectious diarrhea in adults and can be responsible for large outbreaks. nosocomial c. difficile infection results in an increased length of stay in hospital ranging from 8 to 21 days. risk factors for c. difficile-associated diarrhea in ...200111591202
laboratory diagnosis of clostridium difficile disease.the laboratory diagnosis of clostridium difficile-associated disease (cdad) is based on culture and toxin detection in fecal specimens. culture is performed on a commercially available selective media. c. difficile colony morphology is typical when viewed under a dissecting microscope. definitive identification is best obtained by gas liquid chromatography. culture is very sensitive but, when used alone without toxin testing, it leads to low specificity and misdiagnosis of cdad when high rates o ...200111591203
how to detect clostridium difficile variant strains in a routine laboratory.toxin a-negative, toxin b-positive strains (a-/b+) are the best studied examples of clostridium difficile variant strains. in addition, there are some other groups of variant c. difficile strains that produce both toxins (a+/b+) or are non-cytotoxic (a-/b-) but differ from the reference strain vpi 10463 in their toxin genes. here we describe two simple methods (amplification of the tcda gene and amplification of the binary toxin gene cdta) which can be used in rapid screening for variant c. diff ...200111591204
the pathogenicity of clostridium difficile.it is now well established that the major virulence factors of c. difficile are the two toxins a and b. however, the organism possesses an array of other putative virulence factors that may be important for localisation within the colon, and in evasion of the immune system. it has been observed that certain types of c. difficile are more commonly found causing disease than others, and this seems to be independent of toxin production. is this simply a reflection of their abundance in the hospital ...200111591205
typing of clostridium difficile.clostridium difficile is primarily recognised as a nosocomially acquired pathogen manifesting in gastrointestinal disease subsequent to the patient receiving broad-spectrum antibiotics. infection can be sporadic, but outbreaks commonly occur within a ward or hospital as a result of cross-infection. since the 1980s, the epidemiology of c. difficile disease has been studied by the application of many different typing or fingerprinting methods; these, and the lessons learned, are reviewed herein.200111591206
mathematical modeling of clostridium difficile infection.clostridium difficile diarrhea is a major cause of morbidity and mortality in hospitals. however, the number of cases in an outbreak is usually relatively small. this precludes many traditional statistical methods of modeling epidemics. stochastic models are designed to deal with small numbers and are promising methods of understanding c. difficile epidemiology. this is illustrated by a reversible jump markov chain monte carlo model based on the herd immunity hypothesis of c. difficile outbreaks ...200111591207
characteristics of clostridium difficile strains isolated from asymptomatic individuals and from diarrheal patients.to characterise genotypes of clostridium difficile strains isolated from asymptomatic individuals and patients with diarrhea.200111591208
clonal dissemination of a toxin-a-negative/toxin-b-positive clostridium difficile strain from patients with antibiotic-associated diarrhea in poland.to determine the incidence of toxin-a-negative/toxin-b-positive clostridium difficile strains and their genetic relatedness in the feces of patients suffering from antibiotic-associated diarrhea (aad) in polish hospitals.200111591209
clostridium difficile cytotoxin b in adults with diarrhea: a comparison of patients treated or not treated with antibiotics prior to infection.to study the detection rate of clostridium difficile cytotoxin b in stool specimens from adults with diarrhea as related to previous antimicrobial treatment.200111591210
clinical microbiological case: a heart transplant recipient with diarrhea and abdominal pain. recurring c. difficile infection. 200111591211
extra-intestinal infections caused by clostridium difficile.the objective of this paper was to investigate the incidence of extra-intestinal infections caused by clostridium difficile. during a 10-year period, the microbiology laboratory of our institution isolated 2034 isolates of c. difficile. of the 2034 isolates, 21 (1.08%) were obtained from extra-intestinal sources. this represents an incidence of extra-intestinal isolation of four cases per 100 000 admissions. we were able to review the records of 17 patients for our study. the isolates in 12 pati ...200111591212
iron-sulfur flavoprotein (isf) from methanosarcina thermophila is the prototype of a widely distributed family.a total of 35 homologs of the iron-sulfur flavoprotein (isf) from methanosarcina thermophila were identified in databases. all three domains were represented, and multiple homologs were present in several species. an unusually compact cysteine motif ligating the 4fe-4s cluster in isf is conserved in all of the homologs except two, in which either an aspartate or a histidine has replaced the second cysteine in the motif. a phylogenetic analysis of isf homologs identified four subgroups, two of wh ...200111591665
modulation of cox-2 expression by statins in human aortic smooth muscle cells. involvement of geranylgeranylated proteins.cyclooxygenase (cox)-2 and cox-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a (hmg coa) reductase, which is crucial in cholesterol biosynthesis. recently, cholesterol-independent effects of statins have been described. in this study, we evaluated the effect of two inhibitors of hmg coa reductase, mevastatin and lovastatin, on the production of prostacyclin and the ...200111591701
decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.we explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous clostridium difficile colitis with ileus and toxic megacolon.200111591962
[clostridium difficile reactive arthritis]. 200111598549
clinical quiz. an ileocolonic intussusception associated with c. difficile infection. 200111601434
insulin stimulates actin comet tails on intracellular glut4-containing compartments in differentiated 3t3l1 adipocytes.incubation of isolated glut4-containing vesicles with xenopus oocyte extracts resulted in a guanosine 5'-[gamma-thio]triphosphate (gtp gamma s) and sodium orthovanadate stimulation of actin comet tails. the in vitro actin-based glut4 vesicle motility was inhibited by both latrunculin b and a dominant-interfering n-wasp mutant, n-wasp/delta vca. preparations of gently sheared (broken) 3t3l1 adipocytes also displayed gtp gamma s and sodium orthovanadate stimulation of actin comet tails on glut4 in ...200111606595
pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance.many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.200111667952
reduced susceptibility of clostridium difficile to metronidazole. 200111679570
what is an appropriate control group to identify risk factors for clostridium difficile-associated diarrhoea? 200111679574
[what is your diagnosis? pseudomembranous colitis]. 200111680119
bacterial protein toxins inhibiting low-molecular-mass gtp-binding proteins.the rho gtpases, which belong to the ras superfamily of low-molecular-mass gtp-binding proteins, are the preferred intracellular targets of bacterial protein toxins. the rho gtpases rhoa/b/c, rac1/2 and cdc42 are the master regulators of the actin cytoskeleton. clostridium difficile toxins a and b, the causative agents of the antibiotic-associated pseudomembranous colitis, are intracellularly acting cytotoxins which mono-glucosylate the rho gtpases. clostridium botulinum c3 toxin, which is not r ...200111680784
nosocomial outbreak of clostridium difficile-associated diarrhoea due to a clindamycin-resistant enterotoxin a-negative strain.a clindamycin-resistant toxin a-negative, toxin b-positive clostridium difficile strain caused an outbreak among 24 hospitalized patients at the department of surgery, the intensive care unit, and the department of internal medicine of an 800-bed academic hospital. nineteen patients had undergone a surgical intervention and all 24 patients received at least one dose of antibiotics prior to the development of clostridium difficile-associated diarrhoea. twenty-seven episodes of clostridium diffici ...200111681431
[recurrent fatal pseudomembranous colitis].clostridium difficile pseudomembranous colitis may trace a fulminent course and require surgery.200111688204
human infections caused by glycopeptide-resistant enterococcus spp: are they a zoonosis?following the detection of glycopeptide-resistant enterococci (gre) in 1986 and their subsequent global dissemination during the 1990s, many studies have attempted to identify the reservoirs and lines of resistance transmission as a basis for intervention. the eradication of reservoirs and the prevention of gre spread is of major importance for two reasons: (i) the emergence of high-level glycopeptide resistance in invasive enterococcal clinical isolates that are already multiresistant, has left ...200111688531
limitations of presently available glycopeptides in the treatment of gram-positive infection.the glycopeptide antibacterial drugs vancomycin and teicoplanin are widely used in hospitals for therapy of severe or multiresistant gram-positive infections, notably staphylococcal, enterococcal and rarely pneumococcal. vancomycin has also been used in the management of clostridium difficile enteropathy. the incidence and potential for resistance differ between agents. the in vitro activity, pharmacokinetics and clinical use of glycopeptide, as well as epidemiology of glycopeptide resistance ar ...200111688535
antibiotic-associated diarrhea and clostridium difficile colitis: an update.c. difficile colitis ranges from mild diarrhea to life-threatening "toxic" illness with fever, severe diarrhea, and abdominal pain. a colitis, frequently with a pseudomembrone, is the characteristic finding on sigmoidoscopy and is caused by one of more toxins elaborated by the organism clostridium difficile. the clinical syndrome is not specific and can be mimicked by other colonic infections, inflammatory bowel disease, radiation colitis, or ischemic colitis. the diagnosis should be suspected i ...200111692783
pathogenesis of infectious diarrhea.a brief overview of some of the main features involved in normal physiological bi-directional absorption and secretion of fluid in the gut is given, including the nature and cellular location of key enzymes, ion pumps, symports, antiports and diffusion channels; the microanatomy of intestinal villous vasculature and the dynamics of villus blood flow, which together generate hypertonic zones in villus tip regions; and the production, differentiation, escalator movement (from crypt to villus tip) ...200111694903
enhancement of survival by lpa via erk1/erk2 and pi 3-kinase/akt pathways in a murine hepatocyte cell line.first published september 5, 2001; 10.1152/ajpcell.00077.2001.-protective mechanisms for lysophosphatidic acid (lpa) against cell death caused by clostridium difficile toxin, or tumor necrosis factor-alpha (tnf-alpha) plus d-galactosamine, were investigated in a murine hepatocyte cell line aml12 expressing edg2 lpa receptor. in these models of hepatocellular injury, lpa prevented hepatocyte damage, suppressed apoptosis, and enhanced cell survival in a dose-dependent fashion. the protective effec ...200111698260
stimulation of m3 muscarinic receptors induces phosphorylation of the cdc42 effector activated cdc42hs-associated kinase-1 via a fyn tyrosine kinase signaling pathway.the tyrosine kinase, activated cdc42hs-associated kinase-1 (ack-1), is a specific effector of the rho family gtpase cdc42. gtp-bound cdc42 has been shown to facilitate neurite outgrowth elicited by activation of muscarinic cholinergic receptors (machrs). because tyrosine kinase activity is a requirement for neuritogenesis in several cell systems, we investigated whether endogenous machrs (principally of the m3 subtype) expressed in human sh-sy5y neuroblastoma cells would signal to ack-1. incubat ...200111087735
modification of surface histidine residues abolishes the cytotoxic activity of clostridium difficile toxin a.clostridium difficile toxin a displays both cytotoxic and enterotoxic activities. it has recently been demonstrated that toxin a exerts its cytotoxic effect by the glucosylation of the small gtp-binding proteins of the rho family. diethyl pyrocarbonate, at ph 7.0, was used to chemically modify exposed histidine residues on toxin a. modification of toxin a with diethyl pyrocarbonate abolished both its cytotoxic activity and the ability of the toxin to bind zn-sepharose gel. treatment of toxin a w ...200110978751
absence of intestinal secretion on supernatants from macrophages stimulated with clostridium difficile toxin b on rabbit ileum.several studies have documented the involvement of both clostridium difficile, toxins, a and b in the pathogenesis of antibiotic-associated diarrhea. recently, we demonstrated that il-1 beta is the intestinal secretory factor released by macrophages stimulated with toxin a. the aim of this study was to evaluate the importance of macrophages stimulated with toxin b on rabbit ileal ion transport. the changes in ion transport were analyzed by studying the short-circuit current of the rabbit ileal m ...200110978752
frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study.the frequency of antibiotic-associated diarrhoea (aad) and clostridium difficile-associated diarrhoea (cdad) was prospectively determined in a population of 2462 patients recruited from five swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. aad developed in 4.9% of the treated patients. faecal samples were obtained from 69% of patients with aad and 55.4% were positive for c. difficile cytotoxin b. the frequency of ...200111152430
low ph-induced formation of ion channels by clostridium difficile toxin b in target cells.clostridium difficile toxin b (269 kda), which is one of the causative agents of antibiotic-associated diarrhea and pseudomembranous colitis, inactivates rho gtpases by glucosylation. here we studied the uptake and membrane interaction of the toxin with eukaryotic target cells. bafilomycin a1, which prevents acidification of endosomal compartments, blocked the cellular uptake of toxin b in chinese hamster ovary cells cells. extracellular acidification (ph </= 5.2) induced uptake of toxin b into ...200111152463
cytomegalovirus infection as a cause of pseudomembrane colitis: a report of four cases.pseudomembranous colitis is very commonly encountered in patients with acquired immune deficiency syndrome (aids), and has been characteristically associated with clostridium difficile infection. we present four cases of aids-related diarrhea and pseudomembrane formation on endoscopy with pathologic features consistent with cytomegalovirus (cmv) colitis. our findings indicate that cmv colitis should be considered in the differential diagnosis of pseudomembranous colitis in immunocompromised pati ...200111154179
age and disease related changes in intestinal bacterial populations assessed by cell culture, 16s rrna abundance, and community cellular fatty acid profiles.the normal intestinal microflora plays an important role in host metabolism and provides a natural defence mechanism against invading pathogens. although the microbiota in adults has been extensively studied, little is known of the changes that occur in the microflora with aging. these may have important consequences in elderly people, many of whom are receiving antibiotic therapy and who are most susceptible to intestinal dysbiosis.200111156640
protection from gastrointestinal diseases with the use of probiotics.probiotics are nonpathogenic microorganisms that, when ingested, exert a positive influence on the health or physiology of the host. they can influence intestinal physiology either directly or indirectly through modulation of the endogenous ecosystem or immune system. the results that have been shown with a sufficient level of proof to enable probiotics to be used as treatments for gastrointestinal disturbances are 1) the good tolerance of yogurt compared with milk in subjects with primary or se ...200111157353
in vitro activity of new quinolones against clostridium difficile.we evaluated the in vitro activities of ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and ciprofloxacin against clostridium difficile. the mic(90) was 128 mg/l for ofloxacin and levofloxacin, 64 mg/l for ciprofloxacin, 16 mg/l for grepafloxacin and 8 mg/l for trovafloxacin. thirty per cent of isolates were resistant to trovafloxacin, and rates of resistance to ofloxacin, levofloxacin, grepafloxacin and ciprofloxacin were considerably higher. none of the antimicrobials studied would be a ...200111157906
antibiotic activity against genotypically distinct and indistinguishable clostridium difficile isolates. 200111157920
demonstration that the group ii intron from the clostridial conjugative transposon tn5397 undergoes splicing in vivo.previous work has identified the conjugative transposon tn5397 from clostridium difficile. this element was shown to contain a group ii intron. tn5397 can be conjugatively transferred from c. difficile to bacillus subtilis. in this work we show that the intron is spliced in both these hosts and that nonspliced rna is also present. we constructed a mutation in the open reading frame within the intron, and this prevented splicing but did not prevent the formation of the circular form of the conjug ...200111157942
comparison of toxinotyping and pcr ribotyping of clostridium difficile strains and description of novel toxinotypes.toxinotyping and pcr ribotyping are two methods that have been used to type clostridium difficile isolates. toxinotyping is based on pcr-rflp analysis of a 19 kb region encompassing the c. difficile pathogenicity locus. pcr ribotyping is based on comparison of patterns of pcr products of the 16s-23s rrna intergenic spacer region. representative strains (101) from a c. difficile pcr ribotype library and 22 strains from previously described toxinotypes were analysed to compare ribotyping with toxi ...200111158361
safety and immunogenicity of increasing doses of a clostridium difficile toxoid vaccine administered to healthy adults.clostridium difficile is a major cause of nosocomial diarrhea in industrialized countries. although most illnesses respond to available therapy, infection can increase morbidity, prolong hospitalization, and produce life-threatening colitis. vaccines are being explored as an alternative means for protecting high-risk individuals. we assessed the safety, immunogenicity, and dose response of a parenteral vaccine containing c. difficile toxoids a and b. thirty healthy adults were assigned to receiv ...200111159994
rac and phosphatidylinositol 3-kinase regulate the protein kinase b in fc epsilon ri signaling in rbl 2h3 mast cells.fcepsilonri signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (pi3-kinase) and the small gtpase rac. here, we studied the functional relationship among pi3-kinase, its effector protein kinase b (pkb), and rac using inhibitors of pi3-kinase and toxins inhibiting rac. wortmannin, an inhibitor of pi3-kinase, blocked fcepsilonri-mediated tyrosine phosphorylation of phospholipase cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminid ...200111160204
groel (hsp60) of clostridium difficile is involved in cell adherence.previous results have demonstrated that adherence of clostridium difficile to tissue culture cells is augmented by various stresses; this study focussed on whether the groel heat shock protein is implicated in this process. the 1940 bp groesl operon of c. difficile was isolated by pcr. the 1623 bp groel gene is highly conserved between various c. difficile isolates as determined by rflp-pcr and dna sequencing, and the operon is present in one copy on the bacterial chromosome. the 58 kda groel pr ...200111160803
cytosolic delivery and characterization of the tcdb glucosylating domain by using a heterologous protein fusion.tcdb from clostridium difficile glucosylates small gtpases (rho, rac, and cdc42) and is an important virulence factor in the human disease pseudomembranous colitis. in these experiments, in-frame genetic fusions between the genes for the 255 amino-terminal residues of anthrax toxin lethal factor (lfn) and the tcdb(1-556) coding region were constructed, expressed, and purified from escherichia coli. lfntcdb(1-556) was enzymatically active and glucosylated recombinant rhoa, rac, cdc42, and substra ...200111119561
comparative in vitro activities of abt-773 against 362 clinical isolates of anaerobic bacteria.the activity of abt-773, a novel ketolide antibiotic, against clinical isolates of anaerobic bacteria was determined and compared to the activities of other antimicrobial agents. mics at which 90% of isolates were inhibited (mic(90)s) were </=0.06 microg/ml for actinomyces spp., clostridium perfringens, peptostreptococcus spp., propionibacterium spp., and porphyromonas spp. the mic(50)s and mic(90)s were </=0.06 and >32 microg/ml, respectively, for eubacterium spp., lactobacillus spp., clostridi ...200111120995
randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients.in a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. more baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; p=.03). initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. after addition ...200111170945
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