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on the atp-dependent activation of the radical enzyme (r)-2-hydroxyisocaproyl-coa dehydratase.members of the 2-hydroxyacyl-coa dehydratase enzyme family catalyze the β,α-dehydration of various coa-esters in the fermentation of amino acids by clostridia. abstraction of the nonacidic β-proton of the 2-hydroxyacyl-coa compounds is achieved by the reductive generation of ketyl radicals on the substrate, which is initiated by the transfer of an electron at low redox potentials. the highly energetic electron needed on the dehydratase is donated by a [4fe-4s] cluster containing atpase, termed a ...201222827463
clostridium difficile outbreaks: prevention and treatment strategies.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 n ...201222826646
a woman with community-acquired clostridium difficile infection. 201222826000
impact of a hospital-wide hand hygiene initiative on healthcare-associated infections: results of an interrupted time series.evidence that hand hygiene (hh) reduces healthcare-associated infections has been available for almost two centuries. yet hh compliance among healthcare professionals continues to be low, and most efforts to improve it have failed.201222822243
reactive arthritis: developments and challenges in diagnosis and treatment.reactive arthritis (rea) has traditionally been described as a nonseptic arthritis occurring in the joint following an extra-articular bacterial infection. this concept became clinically associated with antecedent infections of either the gastrointestinal or genitourinary tract. yet this operational definition of rea has led to diagnostic uncertainty in different clinical settings. there are several scenarios in which the rea has been complex. one is in the sapho syndrome, which shares many feat ...201222821199
clostridium difficile ribotype does not predict severe infection.studies of clostridium difficile outbreaks suggested that certain ribotypes (eg, 027 and 078) cause more severe disease than other ribotypes. a growing number of studies challenge the validity of this hypothesis.201222972866
systematic review and meta-analysis of outcomes following emergency surgery for clostridium difficile colitis.only a small proportion of patients with severe clostridium difficile infection (cdi) undergo emergency surgery, the timing and nature of which is unclear. the aim of this study was to describe the operations performed and to identify factors predictive of death following emergency surgery for cdi.201222972525
in vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy.histiocytes have a pivotal role in wound repair and intestinal epithelial recovery - the most important goal to sustain gut functionality. yet, an in vivo description of colonic histiocytes by confocal laser endomicroscopy (cle) is missing. here, we report the case of a 45-years-old male patient who was referred to our clinic with weight loss and a history of two consecutive clostridium difficile colitis episodes, the latter cured 3 wk before present admission. stool microbiology was negative. c ...201222969212
comparison of bacterial quantities in left and right colon biopsies and faeces.to compare quantities of predominant and pathogenic bacteria in mucosal and faecal samples.201222969206
proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis.there is increasing evidence that proton pump inhibitors (ppis) increase the rate of infections in patients with decompensated cirrhosis.201222966967
a first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study to assess the safety and tolerability of lff571 in healthy volunteers.clostridium difficile is the leading cause of hospital-acquired infectious diarrhea. lff571 is a novel inhibitor of the prokaryotic translation elongation factor tu and is active against a range of bacterial species, including c. difficile. this first-in-human study investigated the safety and pharmacokinetics of single and multiple ascending oral doses of lff571 in healthy subjects. this was a randomized, double-blind, placebo-controlled study. except for one cohort, lff571 was given with a hig ...201222964250
reducing adverse effects of proton pump inhibitors.proton pump inhibitors effectively treat gastroesophageal reflux disease, erosive esophagitis, duodenal ulcers, and pathologic hypersecretory conditions. proton pump inhibitors cause few adverse effects with short-term use; however, long-term use has been scrutinized for appropriateness, drug-drug interactions, and the potential for adverse effects (e.g., hip fractures, cardiac events, iron deficiency, clostridium difficile infection, pneumonia). adults 65 years and older are more vulnerable to ...201222962914
daily disinfection of high-touch surfaces in isolation rooms to reduce contamination of healthcare workers' hands.in a randomized nonblinded trial, we demonstrated that daily disinfection of high-touch surfaces in rooms of patients with clostridium difficile infection and methicillin-resistant staphylococcus aureus colonization reduced acquisition of the pathogens on hands after contacting high-touch surfaces and reduced contamination of hands of healthcare workers caring for the patients.201222961024
epidemiology and healthcare costs of incident clostridium difficile infections identified in the outpatient healthcare setting.to describe the epidemiology and healthcare costs of clostridium difficile infection (cdi) identified in the outpatient setting.201222961023
in vitro evaluation of the antimicrobial activity of a range of probiotics against pathogens: evidence for the effects of organic acids.the aim of this study was to investigate the antimicrobial properties of fifteen selected strains belonging to the lactobacillus, bifidobacterium, lactococcus, streptococcus and bacillus genera against gram-positive and gram-negative pathogenic bacteria. in vitro antibacterial activity was initially investigated by an agar spot method. results from the agar spot test showed that most of the selected strains were able to produce active compounds on solid media with antagonistic properties against ...201222959627
mortality and clostridium difficile infection: a review. 201222958425
antimicrobial stewardship in scotland: impact of a national programme.the scottish antimicrobial prescribing group (sapg) was established by the scottish government in 2008 to lead the first national initiative to actively address antimicrobial stewardship. healthcare associated infection (hai) is a priority in scotland and the work of sapg contributes to the national hai delivery plan. sapg's early work has focused on restricting the use of antibiotics associated with a high risk of clostridium difficile infection (cdi) and development of national prescribing ind ...201222958296
prolongation of length of stay and clostridium difficile infection: a review of the methods used to examine length of stay due to healthcare associated infections. 201222958238
clostridium difficile spore-macrophage interactions: spore survival.clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. during the course of clostridium difficile infections (cdi), c. difficile undergoes sporulation and releases spores to the colonic environment. the elevated relapse rates of cdi suggest that c. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment.201222952726
comparison of bd geneohm cdiff and seegene seeplex ace pcr assays using toxigenic clostridium difficile culture for direct detection of tcdb from stool specimens.we evaluated the performances of 2 pcr assays (bd geneohm and seegene ace) for direct detection of tcdb from stool specimens. the concordance rate between bd and seegene was 96.3%. the sensitivities, specificities, positive predictive values (ppvs), and negative predictive values (npvs) of bd and seegene were 95.7%, 96.5%, 91.8%, and 98.2% and 90.0%, 97.1%, 92.6%, and 96.0%, respectively.201222952270
a novel use of rectal swab to test for clostridium difficile infection by real-time pcr. 201222951884
clostridium difficile detection: identification of colonization, subclinical and overt disease. 201222951306
prevalence and distribution of clostridium difficile pcr ribotypes in cats and dogs from animal shelters in thuringia, germany.clostridium difficile is an important cause of nosocomial diarrhoea in humans. pet animals and livestock are discussed as potential natural reservoirs and sources of infection. in this study faecal samples from dogs and cats were collected at 10 animal shelters in thuringia, germany. c. difficile was isolated from 9 out of 165 (5.5%) canine and 5 out of 135 (3.7%) feline samples. five pcr ribotypes (010, 014/020, 039, 045, slo 066) were identified. pcr ribotypes 010 and 014/020 were detected in ...201222951303
evaluation of the xpert clostridium difficile assay for the diagnosis of clostridium difficile infection.infection with clostridium difficile is a growing concern because of the increasing prevalence and spread of nosocomial infections. emergence of the hypervirulent 027/nap1/bi strain is also notable. existing diagnostic methods have low sensitivity or are time-consuming. therefore, establishing a rapid and accurate microbiological diagnostic assay is needed. we evaluated the xpert c. difficile assay (xpert cd assay; cepheid, usa) to detect toxigenic c. difficile. this assay is a real-time multipl ...201222950071
clostridium difficile colitis and neutropenic fever associated with docetaxel chemotherapy in a patient with advanced extramammary paget's disease.extramammary paget's disease is a rare cutaneous malignant neoplasm. previous studies indicated the efficacy of docetaxel in advanced cases. the common side effects of docetaxel are usually tolerable and seldom life-threatening. we experienced a case of severe pseudomembranous colitis and neutropenic fever that developed just after the first cycle of docetaxel chemotherapy. to the best of our knowledge, there are few reports of pseudomembranous colitis associated with docetaxel administration fo ...201222949901
morbidity and mortality associated with clostridium difficile ribotype 078: a case-case study.the morbidity and mortality associated with clostridium difficile ribotype 078 were examined by comparison with other known outbreak strains. a healthcare interaction within eight weeks of a positive specimen significantly increased the likelihood of ribotype 078 compared with ribotype 027. individuals with ribotype 078 also tended to come from community sources, have a hospital stay post specimen similar to ribotype 027 and a lower 30-day mortality, but these differences were not statistically ...201222947650
[risk factors of clostridium difficile-associated diarrhea in children].to explore the risk factors of clostridium difficile-associated diarrhea (cdad) in children.201222944235
fidaxomicin versus vancomycin for clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing clostridium difficile infection (cdi) and superior for reducing cdi recurrences. in both studies, adults with active cdi were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. post hoc exploratory intent-to-treat (itt) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-anal ...201222752871
predictors of first recurrence of clostridium difficile infection: implications for initial management.symptomatic recurrence of clostridium difficile infection (cdi) occurs in approximately 20% of patients and is challenging to treat. identifying those at high risk could allow targeted initial management and improve outcomes. adult toxin enzyme immunoassay-positive cdi cases in a population of approximately 600,000 persons from september 2006 through december 2010 were combined with epidemiological/clinical data. the cumulative incidence of recurrence ≥ 14 days after the diagnosis and/or onset o ...201222752869
electrospray ionization-induced protein unfolding.electrospray ionization mass spectrometry (esi-ms) measurements were performed under a variety of solution conditions on a highly acidic sub-fragment (b3c) of the c-terminal carbohydrate-binding repeat region of clostridium difficile toxin b, and two mutants (b4a and b4b) containing fewer acidic residues. esi-ms measurements performed in negative ion mode on aqueous ammonium acetate solutions of b3c at low ionic strength (i < 80 mm) revealed evidence, based on the measured charge state distribut ...201222993046
patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent clostridium difficile infection.fecal microbiota transplantation (fmt), a safe, effective alternative therapy for recurrent clostridium difficile infection (cdi), is infrequently used, in part because of an assumption that patients are unwilling to consider fmt because of its unappealing nature.201222990849
improving the quality of antibiotic prescribing in the nhs by developing a new antimicrobial stewardship programme: start smart--then focus.there has been dramatic change in antibiotic use in english hospitals. data from 2004 and 2009 show that the focus on reducing fluoroquinolone and second- and third-generation cephalosporin use seems to have been heeded in nhs secondary care, and has been associated with a substantial decline in hospital clostridium difficile rates. however, there has been a substantial increase in use of co-amoxiclav, carbapenems and piperacillin/tazobactam. in primary care, antibiotic prescribing fell markedly ...201222855879
corticosteroids in the treatment of pseudomembranous colitis: a report of 3 cases.clostridium difficile associated diarrhoea has been an increasing problem in the last decade in the uk and is a cause of significant morbidity. at the most severe end of the spectrum it causes pseudomembranous colitis which has a significant associated mortality rate and can be refractory to standard treatments. here we present three cases of proven pseudomembranous colitis in which systemic corticosteroids were used as an adjunct to treatment, raising the possibility of a new treatment option f ...201227785209
clostridium difficile clinical isolates exhibit variable susceptibility and proteome alterations upon exposure to mammalian cationic antimicrobial peptides.clostridium difficile is a leading cause of hospital-acquired bacterial infections in the united states, and the increased incidence of recurrent c. difficile infections is particularly problematic. the molecular mechanisms of c. difficile colonization, including its ability to evade host innate immune responses, is poorly understood. we hypothesized that epidemic-associated c. difficile clinical isolates would exhibit increased resistance to mammalian, gut-associated, cationic antimicrobial pep ...201223017940
attributing cause of death for patients with clostridium difficile infection. 201223017180
multicenter clinical evaluation of the portrait toxigenic c. difficile assay for detection of toxigenic clostridium difficile strains in clinical stool specimens.we compared the portrait toxigenic c. difficile assay, a new semiautomated sample-to-result molecular test, to a toxigenic bacterial culture/cell cytotoxin neutralization assay (tbc/ccna) for the detection of toxigenic clostridium difficile in 549 stool specimens. stool specimens were also tested by one of three alternative fda-cleared molecular tests for toxigenic c. difficile (xpert c. difficile, illumigene c. difficile, or geneohm cdiff). the sensitivities and specificities of the molecular t ...201223015667
proton pump inhibitors: potential adverse effects.this review summarizes adverse effects of potential proton pump inhibitors (ppis), including nutritional deficiencies (b12 and magnesium), rebound acid hypersecretion, acute interstitial nephritis, gastric carcinoid tumor, cardiovascular risk with clopidogrel and ppi coprescription, bone fractures, enteric infections and pneumonia. an epidemiologic framework is applied to assess clinical relevance and reinforce best practice recommendations.201223010681
a pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin.management of cardiac intensive care unit (icu) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. this pilot randomised trial investigated whether or not, in the icu, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis.201223010339
outcomes in patients tested for clostridium difficile toxins.clostridium difficile testing is shifting from toxin detection to c. difficile detection. yet, up to 60% of patients with c. difficile by culture test negative for toxins and it is unclear whether they are infected or carriers. we reviewed medical records for 7046 inpatients with a c. difficile toxin test from 2005 to 2009 to determine the duration of diarrhea and rate of complications and mortality among toxin-positive (toxin+) and toxin- patients. overall, toxin- patients had less severe diarr ...201223009731
ppi therapy and albumin are better predictors of recurrent clostridium difficile colitis than choice of antibiotics.recurrent clostridium difficile colitis (rcdc) is common, but data regarding recurrence rates and predisposing factors are sparse.201223007285
[adverse events associated with long-term use of proton pump inhibitors].proton pump inhibitors (ppi) remain the leading therapy for acid-related disorders. long-term ppi use increases the risk of pneumonia and enteric bacterial infections and of nosocomial clostridium difficile-associated diarrhoea. ppis do not lead to vitamin b12 or iron deficiencies and do not induce malignancies or increase the risk of major birth defects. prolonged ppi use may be a weak risk factor for certain fractures and results in hypergastrinaemia and parietal cell hyperplasia leading to re ...201223006222
different antibiotic resistance and sporulation properties within multiclonal clostridium difficile pcr ribotypes 078, 126, and 033 in a single calf farm.clostridium difficile strains were sampled periodically from 50 animals at a single veal calf farm over a period of 6 months. at arrival, 10% of animals were c. difficile positive, and the peak incidence was determined to occur at the age of 18 days (16%). the prevalence then decreased, and at slaughter, c. difficile could not be isolated. six different pcr ribotypes were detected, and strains within a single pcr ribotype could be differentiated further by pulsed-field gel electrophoresis (pfge) ...201223001653
the impact of mechanical bowel preparation on postoperative complications for patients undergoing cystectomy and urinary diversion.the benefit of routine mechanical bowel preparation for patients undergoing radical cystectomy is not well established. we compared postoperative complications in patients who did or did not undergo mechanical bowel preparation before radical cystectomy.201222999697
toxic megacolon from fulminant clostridium difficile infection induced by topical silver sulphadiazine.pseudomembranous colitis and toxic megacolon (tm) are well-known complications of clostridium difficile infections. systemic antibiotic is considered as the major risk factor for the development of c difficile colitis. however, topical antibiotics are rarely associated with the infection. as previously thought, the use of topical antibiotic is capable of systemic absorption in damaged and denuded skin; sufficient enough to suppress the normal bowel flora. here, we present an unusual case of tm f ...201222878997
sensitivity of pathogenic and commensal bacteria from the human colon to essential oils.the microbiota of the intestinal tract plays an important role in colonic health, mediating many effects of dietary components on colonic health and during enteric infections. in the context of the increasing incidence of antibiotic resistance in gut bacteria, complementary therapies are required for the prevention and treatment of enteric infections. here we report the potential application of essential oils (eo) and pure eo compounds to improve human gut health. nerolidol, thymol, eugenol and ...201222878397
impact of toxigenic clostridium difficile colonization and infection among hospitalized adults at a district hospital in southern taiwan.the impact of toxigenic clostridium difficile colonization (tcdc) in hospitalized patients is not clear.201222876321
fidaxomicin (dificid), a novel oral macrocyclic antibacterial agent for the treatment of clostridium difficile-associated diarrhea in adults. 201222876085
novel management strategies in the treatment of severe clostridium difficile infection.cdi is increasing in incidence and severity. clinicians must have a low threshold to consider the diagnosis and to treat patients with the clinical syndrome and risk factors before laboratory confirmation of the diagnosis. in patients who have signs of advanced disease, escalation of care with antimicrobial strategies and multidisciplinary care including surgical consultation is necessary. furthermore, lowering the threshold for surgery compared with traditional approaches likely results in impr ...201222873036
in vitro and in vivo activities of the novel ketolide rbx 14255 against clostridium difficile.the mic(90) of rbx 14255, a novel ketolide, against clostridium difficile was 4 μg/ml (mic range, 0.125 to 8 μg/ml), and this drug was found to be more potent than comparator drugs. an in vitro time-kill kinetics study of rbx 14255 showed time-dependent bacterial killing for c. difficile. furthermore, in the hamster model of c. difficile infection, rbx 14255 demonstrated greater efficacy than metronidazole and vancomycin, making it a promising candidate for c. difficile treatment.201222869573
current challenges in antimicrobial resistance and healthcare-associated infections: role and organization of arhai.the uk government specialist advisory committee on antimicrobial resistance and healthcare-associated infections (arhai) was established in 2007. it has responsibility for providing practical and scientific advice to government on healthcare-associated infections (hcais) and to maintain the effectiveness of antimicrobial agents in the treatment and prevention of infection in man and animals. the manner in which this has been approached by arhai is described. in essence, key themes have been defi ...201222855877
recommendations for surveillance priorities for healthcare-associated infections and criteria for their conduct.surveillance and feedback of results to clinical teams is central to performance improvement in managing healthcare-acquired infections. a major role of the advisory committee on antimicrobial resistance and healthcare-associated infections (arhai) is to advise on surveillance priorities. a sub-committee was set up to systematically review existing uk surveillance schemes. the following three systems were examined in detail: mandatory reporting of methicillin-resistant staphylococcus aureus (mrs ...201222855875
policy development for clostridium difficile.the advisory committee on antimicrobial resistance and healthcare associated infection (arhai) was created at the height of the incidence of clostridium difficile infection (cdi). this article describes the role of arhai in the evaluation of laboratory testing for cdi, a related consultation on the legal requirements for manufacturers of in vitro diagnostic medical devices, a cdi healthcare bundle and surveillance of cdi in children.201222855874
fidaxomicin: a new option for the treatment of clostridium difficile infection.the two drugs currently recommended for the treatment of clostridium difficile infection (cdi), namely vancomycin and metronidazole, are both associated with high rates of recurrence of infection. hence there is a need for new treatment options. the novel oral macrocyclic antibiotic fidaxomicin (previously known as par-101, opt-80 and difimicin) was recently approved in the usa and in europe for the treatment of cdi. clinical trials have shown non-inferiority with regard to clinical cure when co ...201222865382
is primary prevention of clostridium difficile infection possible with specific probiotics?the efficacy of probiotics for the prevention of clostridium difficile infection (cdi) is highly controversial, particularly with regard to the prevention of recurrent cdi. we hypothesize that primary prevention of cdi among patients receiving antibiotics might be a more achievable goal for probiotics than prevention in patients with previous cdi where the host flora is markedly altered.201222863358
comparative transcriptional analysis of clinically relevant heat stress response in clostridium difficile strain 630.clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. in order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41 °c versus 37 °c) in c. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. while the transcriptome was relatively resi ...201222860125
surveillance of infection severity: a registry study of laboratory diagnosed clostridium difficile.changing clinical impact, as virulent clones replace less virulent ones, is a feature of many pathogenic bacterial species and can be difficult to detect. consequently, innovative techniques monitoring infection severity are of potential clinical value.201222859914
knowledge of clostridium difficile infection among uk health-care workers: development of a knowledge assessment tool.doctors' knowledge provides the basis to support good practice in infection prevention and control. however, there exists a paucity of validated knowledge assessment tools that can be reliably employed to identify poor knowledge levels of clostridium difficile infection (cdi) within populations of doctors, preventing the effective identification of knowledge deficiencies and focused targeting of educational interventions. here, we describe a development process to validate a novel cdi knowledge ...201222859801
probiotics for infectious diseases: more drugs, less dietary supplementation.according to current definitions, probiotics are live microorganisms that, when ingested in adequate quantities, exert a health benefit to the host. the action of probiotics in the host is exerted by three mechanisms: modulation of the content of gut microbiota; maintenance of the integrity of the gut barrier and prevention of bacterial translocation; and modulation of the local immune response by the gut-associated immune system. regarding their role for the prevention and treatment of infectio ...201222858373
pediatric physicians' knowledge, attitudes, and beliefs regarding clostridium difficile-associated disease prevention, testing, and treatment. 201222854381
repeat stool testing for clostridium difficile using enzyme immunoassay in patients with inflammatory bowel disease increases diagnostic yield.the incidence and severity of clostridium difficile infection (cdi) in patients with inflammatory bowel disease (ibd) is increasing. cdi is diagnosed by toxin enzyme immunoassay (eia) or real-time polymerase chain reaction (pcr) performed on stool samples. an earlier study evaluating eia in ibd patients with cdi suggested that more than one stool sample be tested to increase diagnostic yield. we investigated whether repeat stool testing improves diagnostic accuracy for cdi in hospitalized ibd pa ...201222852871
evaluation of an oral suspension of vp20621, spores of nontoxigenic clostridium difficile strain m3, in healthy subjects.vp20621, spores of nontoxigenic clostridium difficile (ntcd) strain m3, is protective against challenge with toxigenic strains in hamsters. human administration and colonization may prevent primary c. difficile infection (cdi) or recurrent cdi. healthy adult subjects 18 to 45 years old or ≥60 years old received single or multiple doses of an oral suspension of vp20621 (10(4), 10(6), or 10(8) spores) or placebo. group 4 (≥60 years old) received oral vancomycin for 5 days, followed by 14 days of v ...201222850511
impact of hospital-acquired clostridium difficile.to investigate the impact of hospital-acquired clostridium difficile infection (cdi) on hospital costs and patient length of stay.201222849881
higher rates of clostridium difficile infection among smokers.cigarette smoking has been shown to be related to inflammatory bowel disease. we investigated whether smoking affected the probability of developing clostridium difficile infection (cdi).201222848714
colonoscopic versus nasogastric fecal transplantation for the treatment of clostridium difficile infection: a review and pooled analysis.fecal microbiota transplantation (fmt) has been demonstrated to be highly effective for the treatment of recurrent clostridium difficile infection (cdi). however, the best route of administration has not been established. we present a pooled analysis of the reported cases of cdi treated with fmt via colonoscopy or nasogastric tube (ngt) to evaluate treatment efficacy.201222847629
conformational analysis of clostridium difficile toxin b and its implications for substrate recognition.clostridium difficile (c. difficile) is an opportunistic pathogen that can cause potentially lethal hospital-acquired infections. the cellular damage that it causes is the result of two large clostridial cytotoxins: tcda and tcdb which act by glucosylating cytosolic g-proteins, mis-regulation of which induces apoptosis. tcdb is a large flexible protein that appears to undergo significant structural rearrangement upon accommodation of its substrates: udp-glucose and a rho-family gtpase. to charac ...201222844485
irinotecan (cpt-11) chemotherapy alters intestinal microbiota in tumour bearing rats.intestinal microbiota mediate toxicity of irinotecan (cpt-11) cancer therapies and cause systemic infection after cpt-11-induced loss of barrier function. the intestinal microbiota and their functions are thus potential targets for treatment to mitigate cpt-11 toxicity. however, microbiota changes during cpt-11 therapy remain poorly described. this study analysed changes in intestinal microbiota induced by cpt-11 chemotherapy. qualitative and quantitative taxonomic analyses, and functional analy ...201222844397
clostridium difficile: an emerging pathogen in children.clostridium difficile is emerging as an important enteric pathogen in children. historically considered as an asymptomatic colonizer of the gastrointestinal tract, c. difficile infection (cdi) has not been well-studied in pediatric populations. while asymptomatic carriage remains high among infants, recent epidemiological surveillance has demonstrated a rise in the prevalence of cdi in both healthcare and community settings, particularly in children 1-5 years of age. the pathogenesis of pediatri ...201222935207
determination of serum antibodies to clostridium difficile toxin b in patients with inflammatory bowel disease.clostridium difficile infection has increased in prevalence among patients with inflammatory bowel disease (ibd). serum antibodies against c. difficile toxins have been detected in susceptible populations and may be protective; however, such antibodies have not been previously characterized in ibd patients. this study measured immunoglobulin g antibody levels to c. difficile toxin b in serum from ibd patients in remission and ibd patients in relapse. ibd patients demonstrated significantly highe ...201222933861
[treatment of refractory or recurrent clostridium difficile infection].the incidence and severity of clostridium difficile infection (cdi) has increased over the past decades. it is related to the emergence of hypervirulent strains and increased use of antibiotics. the incidence of refractory cdi to standard therapies and the risk for recurrent cdi are also increasing. current guidelines recommend the first recurrence to be treated with the same agent used for the initial episode. however, data are lacking to support any particular treatment strategy for severe ref ...201222926117
prevalence and genotypic characterization of clostridium difficile from ruminants in switzerland.clostridium difficile is an emerging enteric pathogen of humans and animals with a known main reservoir in the intestinal tract of various warm-blooded animals. this study was carried out to evaluate the prevalence of c. difficile in 150 rectal swab samples collected from cattle and goats in switzerland. the overall prevalence of c. difficile was 6.6%. the isolates belonged to the pcr ribotypes 033, 066, 070, 003, 001 and 137. in addition, the occurrence of c. difficile in faecal samples collect ...201222925279
contribution of spores to the ability of clostridium difficile to adhere to surfaces.clostridium difficile is the commonest cause of hospital-acquired infection in the united kingdom. we characterized the abilities of 21 clinical isolates to form spores; to adhere to inorganic and organic surfaces, including stainless steel and human adenocarcinoma cells; and to germinate. the composition of culture media had a significant effect on spore formation, as significantly more spores were produced in brain heart infusion broth (student's t test; p = 0.018). the spore surface relative ...201222923404
evidence of in vivo prophage induction during clostridium difficile infection.prophages contribute to the evolution and virulence of most bacterial pathogens, but their role in clostridium difficile is unclear. here we describe the isolation of four myoviridae phages, φmmp01, φmmp02, φmmp03, and φmmp04, that were recovered as free viral particles in the filter-sterilized stool supernatants of patients suffering from c. difficile infection (cdi). furthermore, identical prophages were found in the chromosomes of c. difficile isolated from the corresponding fecal samples. we ...201222923402
risk factors for development of clostridium difficile infection due to bi/nap1/027 strain: a meta-analysis.to identify risk factors for the development of clostridium difficile infection (cdi) due to c. difficile bi/nap1/027 strain.201222921930
toward a structural understanding of clostridium difficile toxins a and b.clostridium difficile is a toxin-producing bacterium that is a frequent cause of hospital-acquired and antibiotic-associated diarrhea. the incidence, severity, and costs associated with c. difficile associated disease are substantial and increasing, making c. difficile a significant public health concern. the two primary toxins, tcda and tcdb, disrupt host cell function by inactivating small gtpases that regulate the actin cytoskeleton. this review will discuss the role of these two toxins in pa ...201222919620
"community-acquired clostridium difficile infection: an emerging entity". 201222918999
the continually evolving clostridium difficile species.clostridium difficile is a spore-forming gram-positive bacterium that causes chronic diarrhea and sometimes life-threatening disease mainly in elderly and hospitalized patients. the reported incidence of c. difficile infection has changed dramatically over the last decade and has been related to the emergence of distinct clonal lineages that appear more transmissible and cause more severe infection. these include pcr ribotypes 027, 017 and more recently 078. population biology studies using mult ...201222913354
molecular basis of early stages of clostridium difficile infection: germination and colonization.clostridium difficile infections (cdis) occur when antibiotic therapy disrupts the gastrointestinal flora, favoring infected c. difficile spores to germinate, outgrow, colonize and produce toxins. during cdi, c. difficile vegetative cells initiate the process of sporulation allowing a fraction of the spores to remain adhered to the intestinal surfaces. these spores, which are unaffected by antibiotic therapy commonly used for cdis, then germinate, outgrow and recolonize the host's gi tract causi ...201222913353
tcdc does not significantly repress toxin expression in clostridium difficile 630δerm.in the past decade, clostridium difficile has emerged as an important gut pathogen. symptoms of c. difficile infection range from mild diarrhea to pseudomembranous colitis, sometimes resulting in colectomy or death. the main virulence factors of c. difficile are toxin a and toxin b. besides the genes encoding these toxins (tcda and tcdb), the pathogenicity locus (paloc) also contains genes encoding a sigma factor (tcdr) and a putative anti-sigma factor (tcdc). the important role of tcdr as a sig ...201222912837
utility of perirectal swab specimens for diagnosis of clostridium difficile infection.for 139 patients tested for clostridium difficile infection by polymerase chain reaction, the sensitivity, specificity, positive predictive value, and negative predictive value of testing perirectal swabs vs stool specimens were 95.7%, 100%, 100%, and 99.1%, respectively. for selected patients, perirectal swabs provide an accurate toxigenic c. difficile detection strategy.201222911648
acp journal club: review: proton-pump inhibitors are associated with increased risk for clostridium difficile infection. 201222910967
in vivo selection of rifamycin-resistant clostridium difficile during rifaximin therapy.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.201222908175
fecal microbiota transplantation for fulminant clostridium difficile infection in an allogeneic stem cell transplant patient.we present a case of severe clostridium difficile infection (cdi) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. bowel resection was averted. this is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocomp ...201223121625
a prospective study to examine the epidemiology of methicillin-resistant staphylococcus aureus and clostridium difficile contamination in the general environment of three community hospitals in southern ontario, canada.the hospital environment has been suggested as playing an important role in the transmission of hospital-associated (ha) pathogens. however, studies investigating the contamination of the hospital environment with methicillin-resistant staphylococcus aureus (mrsa) or clostridium difficile have generally focused on point prevalence studies of only a single pathogen. research evaluating the roles of these two pathogens, concurrently, in the general hospital environment has not been conducted. the ...201223136936
efficacy of different cleaning and disinfection methods against clostridium difficile spores: importance of physical removal versus sporicidal inactivation.we tested the effectiveness of disinfectants and wipe methods against clostridium difficile spores. wiping with nonsporicidal agents (physical removal) was effective in removing more than 2.9 log(10) c. difficile spores. wiping with sporicidal agents eliminated more than 3.90 log(10) c. difficile spores (physical removal and/or inactivation). spraying with a sporicide eliminated more than 3.44 log(10) c. difficile spores but would not remove debris.201223143366
effective antimicrobial stewardship in a long-term care facility through an infectious disease consultation service: keeping a lid on antibiotic use.we introduced a long-term care facility (ltcf) infectious disease (id) consultation service (lid service) that provides on-site consultations to residents of a veterans affairs (va) ltcf. we determined the impact of the lid service on antimicrobial use and clostridium difficile infections at the ltcf.201223143354
targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing clostridium difficile disease in mice.relapsing c. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. we show that mice infected with epidemic c. difficile (genotype 027/bi) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. chronic c. difficile 027/bi infection was refractory to vancomyc ...201223133377
evaluation of commercial kits for extraction of dna and rna from clostridium difficile.commercial nucleic acid extraction kits are a cost effective, efficient and convenient way to isolate dna and rna from bacteria. despite the increasing importance of the gastrointestinal pathogen, clostridium difficile, and the increased use of nucleic acids in its identification, characterization, and investigation of virulence factors, no standardized or recommended methods for nucleic acid isolation exist. here, we sought to evaluate 4 commercial dna extraction kits and 3 commercial rna extra ...201223128271
clostridium difficile infection: new insights into management.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 emergin ...201223127735
clostridium difficile infection in patients with chronic kidney disease.to examine the rate of clostridium difficile infection (cdi) and hospital-associated outcomes in a national cohort of hospitalized patients with chronic kidney disease (ckd) and assess the impact of long-term dialysis on outcome in these patients.201223127731
clostridium difficile: the emerging epidemic. 201223127729
outcome of icu patients with clostridium difficile infection.as data from clostridium difficile infection (cdi) in intensive care unit (icu) are still scarce, our objectives were to assess the morbidity and mortality of icu-acquired cdi.201223127327
fidaxomicin for the treatment of clostridium difficile infections.clostridium difficile infection (cdi), also known as c. difficile-associated disease or diarrhoea (cdad), is an important cause of hospital-acquired diarrhoea with disease severity ranging from mild diarrhoea to fulminant colitis. in addition, over 40% of new cases of cdi occur outside hospital. ▾ fidaxomicin (dificlir - astellas), the first antibiotic in a new class called macrocyclics, has recently been licensed for the treatment of c. difficile infection in adults. here we provide a brief ove ...201223154594
[clostridium difficile: is it time to start worrying?]. 201223153414
safety and efficacy of fidaxomicin in the treatment of clostridium difficile-associated diarrhea.clostridium difficile-associated diarrhea (cdad) is the most common cause of healthcare-associated diarrhea. the current recommended treatment regimens of metronidazole and vancomycin have not changed in nearly 25 years. fidaxomicin, an exceedingly narrow spectrum macrolide antibiotic, was recently approved for the treatment of cdad. in phase iii clinical trials, fidaxomicin was noninferior to vancomycin in achieving clinical cure of cdad. furthermore, fidaxomicin was associated with fewer recur ...201223152733
[preliminary investigation of intestinal microflora in patients with hepatic cirrhosis].to examine the differential levels of fecal bifidobacterium, bacteroides, eubacterium rectale-clostridium, escherichia coli, enterococcus, and clostridium difficile between patients with hepatic cirrhosis and healthy controls. fecal samples were collected from 29 patients with hepatic cirrhosis treated in the department of digestive diseases at zunyi hospital between march and december of 2010.201223206299
[recommendations for diagnosis and therapy of colitis caused by clostridium difficile].clostridium difficile infection (cdi) is a disease of varying severity. its manifestations range from mild diarrhea to life-threatening paralytic ileus, painful distension of the large bowel and sepsis. another possible manifestation of the disease is recurrent colitis that can exhaust the patient. for establishing the diagnosis, the patient's stool should be examined with two or three different microbiological methods. immunochemical testing for the presence of clostridial toxins a and b shows ...201223208871
isolation of clostridium difficile from peritoneal fluid. 201223163311
current and emerging management options for clostridium difficile infection: what is the role of fidaxomicin?until recently, treatment of clostridium difficile infection (cdi) was mainly limited to oral metronidazole and vancomycin, neither of which is optimal. up to 25% of patients with cdi experience recurrence of infection within 30 days following treatment with these agents, while c. 45-65% of these patients experience further (and sometimes multiple) recurrences. recurrent cdi represents a major treatment challenge for which new therapeutic options are sorely needed. fidaxomicin is a first-in-clas ...201223121552
can we identify patients at high risk of recurrent clostridium difficile infection?although most patients with clostridium difficile infection (cdi) can be managed effectively with discontinuation of prescribed antibiotics and additional treatment with oral metronidazole or vancomycin, up to 25% experience disease recurrence, usually within 30 days of treatment. failure to mount a systemic anti-toxin antibody response differentiates patients with cdi and recurrent cdi from symptomless carriers of toxinogenic c. difficile. the immunological senescence that accompanies ageing ma ...201223121551
overcoming barriers to effective recognition and diagnosis of clostridium difficile infection.with the frequency of cases of clostridium difficile infection (cdi) increasing in many developed countries, accurate and reliable laboratory diagnosis of cdi is more important than ever. however, the diagnosis of cdi has been handicapped by the existence of two reference standards, one of which detects c. difficile toxin (cytotoxin assay) and the other only toxigenic strains (cytotoxigenic culture). being relatively slow and laborious to perform, these reference methods were largely abandoned a ...201223121550
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