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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 dna polymerase iiic: basis for activity of antibacterial compounds.based on the finding that aerobic gram-positive antibacterials that inhibit dna polymerase iiic (pol iiic) were potent inhibitors of the growth of anaerobic clostridium difficile (cd) strains, we chose to clone and express the gene for pol iiic from this organism. the properties of the recombinant enzyme are similar to those of related pol iiics from gram-positive aerobes, e.g. b. subtilis. inhibitors of the cd enzyme also inhibited b. subtilis pol iiic, and were competitive with respect to the ...201122844265
clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains.clostridium difficile has long been considered to be a nosocomial pathogen but has emerged in the community in recent years. during infancy, asymptomatic c. difficile colonization is common. however, knowledge of colonization determinants and strain characteristics is limited. we studied the dynamics of c. difficile colonization in healthy infants from the community. determinants of colonization and strain genotypes were also determined in a cohort of infants attending day nurseries.201222843784
[cleaning and disinfection in nursing homes. data on quality of structure, process and outcome in nursing homes in frankfurt am main, germany, 2011].due to the infectious disease prevention act, public health services in germany are obliged to check the infection prevention in hospitals and other medical facilities as well as in nursing homes. in frankfurt/main, germany, standardized control visits have been performed for many years. in 2011 focus was laid on cleaning and disinfection of surfaces. all 41 nursing homes were checked according to a standardized checklist covering quality of structure (i.e. staffing, hygiene concept), quality of ...201222842890
laboratory diagnosis of clostridium difficile associated diarrhoea and molecular characterization of clinical isolates.we evaluated a three-step algorithm for laboratory diagnosis of clostridium difficile-associated diarrhoea (cdad). first, stool specimens were screened using an eia test for glutamate dehydrogenase detection. screen-positive specimens were tested by a rapid cytotoxintoxin a/b assay and subjected to stool culture. all cultures positive for c. difficile underwent toxigenic culture. the results showed that toxigenic culture allowed us to recover 37/156 (24.4%) stool samples harbouring toxigenic c. ...201222842600
epidemic clostridium difficile ribotype 027 in chile. 201222840230
utilizing rapid multiple-locus variable-number tandem-repeat analysis typing to aid control of hospital-acquired clostridium difficile infection: a multicenter study.the early identification of outbreaks is crucial for the control of clostridium difficile infection. this study aimed to determine if the number of hospital-acquired c. difficile infections could be reduced by rapidly typing c. difficile strains using multiple-locus variable-number tandem-repeat analysis (mlva) compared to typing using pcr ribotyping. a total of 16 hospitals were recruited to the study, and all periods of increased incidence (piis) of c. difficile infection were identified. the ...201222837319
refractory clostridium difficile infection successfully treated with tigecycline, rifaximin, and vancomycin.the occurrence of clostridium difficile colitis is on the rise and has become more difficult to manage with standard therapy. thus, the need for alternative treatments is essential. tigecycline is a glycylcycline antibiotic that has been shown to be effective against c. difficile through several published case reports and in in vitro studies. we present a case of c. difficile colitis that failed to respond to metronidazole and oral vancomycin therapy, but improved on a combination of rifaximin, ...201222829841
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
soluble plantain fibre blocks adhesion and m-cell translocation of intestinal pathogens.dietary fibres may have prebiotic effects mediated by promotion of beneficial bacteria. this study explores the possibility that soluble plant fibre may also improve health by inhibiting epithelial adhesion and translocation by pathogenic bacteria. we have focussed on soluble non-starch polysaccharide (nsp) from plantain bananas (musa spp.) which previous studies showed to be particularly effective at blocking escherichia coli epithelial adherence. in vitro and ex vivo studies assessed the abili ...201322818716
reduction in clostridium difficile infection rates after mandatory hospital public reporting: findings from a longitudinal cohort study in canada.the role of public reporting in improving hospital quality of care is controversial. reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of clostridium difficile infection.201222815656
role of fecal clostridium difficile load in discrepancies between toxin tests and pcr: is quantitation the next step in c. difficile testing?direct tests for clostridium difficile are 30-50 % more sensitive than tests for c. difficile toxins but the reasons for this discrepancy are incompletely understood. in addition to toxin degradation and strain differences, we hypothesized that c. difficile concentration could be important in determining whether toxins are detected in fecal samples. we performed standard curves on an fda-approved real-time pcr test for the c. difficile tcdb gene (xpert c. difficile/epi, cepheid) during a prospec ...201222814877
a superior test for diagnosis of clostridium difficile-associated diarrhea in resource-limited settings.in this prospective cohort study, we investigated the prevalence of clostridium difficile-associated diarrhea (cdad) in adult patients with nosocomial diarrhea by performing enzyme immunoassay (eia) for detecting toxins a and b and polymerase chain reaction (pcr) for detecting the presence of the tcdb gene in stool samples. we determined the factors associated with cdad, and the treatment outcome of cdad from may 2010 to january 2011. a total of 175 stool samples were tested by eia and pcr. in t ...201222814157
clostridium difficile infection in the pediatric surgery population.the incidence of clostridium difficile-associated disease (cdad) in the adult population doubled in the past decade, with increasing morbidity and mortality; however, little research has been performed in the pediatric population. we characterized c difficile infection in the pediatric population, with emphasis on the surgical population.201222813801
evaluation of the diagnostic algorithm consisting of enzyme immunoassay for toxins and polymerase chain reaction, for the diagnosis of clostridium difficile-associated diarrhoea.a total of 1631 stool specimens were tested for clostridium difficile toxins a and b using an enzyme immunoassay (eia). c. difficile toxin was detected in 191 (11.7%, 191/1631) cases by eia. among the remaining 1440 cases, 102 cases in patients with either antibiotic-associated diarrhoea or hospitalized patients with unexplained leukocytosis (> 15,000/mm³) and fever (≥ 38°c) even though they did not meet the criteria for diarrhoea, were further assessed using a polymerase chain reaction (pcr) fo ...201222813084
clinical update on nursing home medicine: 2012.this article is the sixth in the series of clinical updates on nursing home care. the topics covered are management of hypertension, antidepressant medications in people with dementia, peripheral arterial disease, probiotics in prevention, and treatment of clostridium difficile-associated diarrhea, frailty, and falls.201222809554
[antimicrobial susceptibility of clinical isolates of aerobic gram-positive cocci and anaerobic bacteria in 2008].the activity of antibacterial agents against aerobic gram-positive cocci (25 genus or species, 1029 strains) and anaerobic bacteria (21 genus or species, 187 strains) isolated from clinical specimens in 2008 at 16 clinical facilities in japan were studied using either broth microdilution or agar dilution method. the ratio of methicillin-resistant strains among staphylococcus aureus and staphylococcus epidermidis was 59.6% and 81.2%, suggesting that resistant strains were isolated at high frequen ...201222808693
second infections independently increase mortality in hospitalized patients with cirrhosis: the north american consortium for the study of end-stage liver disease (nacseld) experience.bacterial infections are an important cause of mortality in cirrhosis, but there is a paucity of multicenter studies. the aim was to define factors predisposing to infection-related mortality in hospitalized patients with cirrhosis. a prospective, cohort study of patients with cirrhosis with infections was performed at eight north american tertiary-care hepatology centers. data were collected on admission vitals, disease severity (model for endstage liver disease [meld] and sequential organ fail ...201222806618
long-term medical management of gastro-esophageal reflux disease: how long and when to consider surgery?gastro-esophageal reflux disease is a chronic, long standing disease. spontaneous remission of gerd is rare and conservative management including life style modification measures is unlikely to relieve symptoms. majority of patients with reflux disease require long-term acid suppressants. proton pump inhibitors are the choice of drugs in management of these patients. the end point of treatment is not clear. duration of treatment is individual based. the symptoms may be intermittent or on most da ...201222803292
a canadian working group report on fecal microbial therapy: microbial ecosystems therapeutics.a working group from across canada comprised of clinician and basic scientists, epidemiologists, ethicists, health canada regulatory authorities and representatives of major funding agencies (canadian institutes of health research and the crohn's and colitis foundation of canada) met to review the current experience with fecal microbial therapy and to identify the key areas of study required to move this field forward. the report highlights the promise of fecal microbial therapy and related synt ...201222803022
in vitro and in vivo characterization of cb-183,315, a novel lipopeptide antibiotic for treatment of clostridium difficile.cb-183,315 is a novel lipopeptide antibiotic structurally related to daptomycin currently in phase 3 clinical development for clostridium difficile-associated diarrhea (cdad). we report here the in vitro mechanism of action, spontaneous resistance incidence, resistance by serial passage, time-kill kinetics, postantibiotic effect, and efficacy of cb-183,315 in a hamster model of lethal infection. in vitro data showed that cb-183,315 dissipated the membrane potential of staphylococcus aureus witho ...201222802252
epidemiological features of clostridium difficile infection among inpatients at hamad general hospital in the state of qatar, 2006-2009.the aim of this retrospective study was to evaluate the epidemiology, clinical course and outcome of clostridium difficile infection among inpatients at hamad general hospital in qatar, from 2006 to 2009. during this period, 123 patients were diagnosed with c. difficile infection and the overall incidence was 1.6/10,000 patient days. the mean age (±sd) of patients was 50.9 ± 21.2 years. the most frequent underlying disease was hypertension 51/123 (41.5%) and 133 prescriptions of antimicrobials w ...201222800937
toxigenic clostridium difficile pcr ribotypes from wastewater treatment plants in southern switzerland.the occurrence of clostridium difficile in nine wastewater treatment plants in the ticino canton (southern switzerland) was investigated. the samples were collected from raw sewage influents and from treated effluents. forty-seven out of 55 characterized c. difficile strains belonged to 13 different reference pcr ribotypes (009, 010, 014, 015, 039, 052, 053, 066, 070, 078, 101, 106, and 117), whereas 8 strains did not match any of those available in our libraries. the most frequently isolated ri ...201222798376
the use of ceftaroline fosamil in methicillin-resistant staphylococcus aureus endocarditis and deep-seated mrsa infections: a retrospective case series of 10 patients.there are many limitations to the current antibiotics used for the treatment of severe methicillin-resistant staphylococcus aureus (mrsa) infections. ceftaroline is a new fifth-generation cephalosporin approved for the treatment of skin and soft tissue infections caused by mrsa and community-acquired pneumonia. we propose that ceftaroline can also be used successfully in more severe mrsa infections, including endocarditis. we conducted a retrospective chart review in a university-affiliated depa ...201322797874
association between antibiotic treatment and outcomes in patients hospitalized with acute exacerbation of copd treated with systemic steroids.antibiotics are widely used in acute exacerbations of copd (ae-copd), but their additional benefit to a therapeutic regimen that already includes steroids is uncertain. we evaluated the association between antibiotic therapy and outcomes among a large cohort of patients treated with steroids who were hospitalized with ae-copd and compared the effectiveness of three commonly used antibiotic regimens.201322797691
lack of enhanced effect of a chlorine dioxide-based cleaning regimen on environmental contamination with clostridium difficile spores.spores of clostridium difficile may play a significant role in transmission of disease within the healthcare environment and are resistant to a variety of detergents and cleaning fluids. a range of environmental cleaning agents has recently become available, many of which claim to be sporicidal. we investigated the effect of changing to a chlorine dioxide-based cleaning regimen on c. difficile environmental contamination and patient infection rates. the prevalence of environmental contamination ...201222795136
the evolution of clostridium difficile infection in cancer patients: epidemiology, pathophysiology, and guidelines for prevention and management.clostridium difficile infection (cdi) has emerged as a significant challenge to the healthcare system. the availability of anti-cancer chemotherapeutic regimens has contemporaneously resulted in a larger population of patients who are susceptible to cdi. the outbreak of a novel, hypervirulent, resistant strain, nap-1/027 as well as resistance to antibiotic therapy have further contributed to an increase in prevalence as well as in disease severity. recent data show high fatality rates in cancer ...201222792862
risk factors for the development of clostridium difficile colitis in a surgical ward.clostridium difficile colitis (cdc) is a nosocomial infection. we attempted to discover the risk factors for the development of cdc in patients admitted to our surgical ward.201222792529
yersinia enterocolitica yopt and clostridium difficile toxin b induce expression of gilz in epithelial cells.glucocorticoid induced-leucine zipper (gilz) has been shown to be induced in cells by different stimuli such as glucocorticoids, il-10 or deprivation of il-2. gilz has anti-inflammatory properties and may be involved in signalling modulating apoptosis. herein we demonstrate that wildtype yersinia enterocolitica which carry the pyv plasmid upregulated gilz mrna levels and protein expression in epithelial cells. infection of hela cells with different yersinia mutant strains revealed that the prote ...201222792400
clostridium difficile infection in the absence of a colon.clostridium difficile (cd) infection is almost always confined to the colon causing a spectrum of illness ranging from diarrhoea to fulminant colitis. cd infection of the small intestine has been described but the identification of cd toxin in the stoma effluent of a patient with an end ileostomy is rare. we describe a 91-year-old woman, with a history of proctocolectomy for ulcerative colitis, presenting with profuse ileostomy diarrhoea after a course of antibiotics. ileostomy effluent was posi ...201022791474
igg antibody response to toxins a and b in patients with clostridium difficile infection.igg antibodies against clostridium difficile toxins a and b were followed in controls and in patients with an initial c. difficile infection (cdi). of the 50 cdi patients, 38 were cured and 12 developed recurrence. compared to controls, patients had significantly lower anti-toxin a and b iggs at inclusion, but the subsequent levels rose slightly regardless of clinical outcome. the results imply that the general serum reactivity against toxins a and b in the population reduces the risk of cdi, wh ...201222787196
changing epidemiology of clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in england.marked increases in clostridium difficile infection (cdi) incidence, driven by epidemic strain spread, is a global phenomenon.201222784871
clostridium difficile infection and proton pump inhibitors.clostridium difficile is an intestinal infection associated with antibiotic use, commonly seen in patients with chronic medical issues. the purpose of this review is to discuss the association of c. difficile-associated diarrhea with use of proton pump inhibitors.201222781139
antimicrobial-associated diarrhoea in three equine referral practices.although antimicrobial-associated diarrhoea (aad) is the most frequently observed adverse effect of antimicrobial therapy in horses, few multicentred studies on the prevalence of aad have been performed.201322779907
anti-tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients.ulcerative colitis (uc) and crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (olt) despite post-transplantation immunosuppressive therapy.201222779779
overutilization of proton-pump inhibitors: what the clinician needs to know.proton-pump inhibitors (ppis) remain the leading evidence-based therapy for upper gastrointestinal disorders, including gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease. the effectiveness of ppis has led to overutilization in multiple treatment arenas, exposing patients to an increasing number of potential risks. the overutilization of ppis in ambulatory care settings is often a result of failure to re-evaluate the need for continuation of therapy, or insufficient use of on-d ...201222778788
new horizons for host defense peptides and lantibiotics.antimicrobial peptides from either microbial sources, or based on host defense peptides (hdps) from higher organisms, show promising activity against human pathogens. lantibiotics have been extensively engineered by either molecular biology approaches or chemistry and both natural and modified entities have been shown to have good efficacy in animal models of infection. amongst hdps either truncated peptides or non-peptide mimetic molecules show substantial promise both for their direct antibiot ...201222776251
prevalence of opportunistic intestinal parasitic infections among hiv-infected patients with low cd4 cells counts in france in the combination antiretroviral therapy era.the use of combination antiretroviral therapy (cart) has dramatically reduced the prevalence of opportunistic infections, however data on the prevalence of intestinal parasitic infections in hiv-infected patients with low cd4 cell counts in the cart era are scarce.201222771183
molecular techniques for diagnosis of clostridium difficile infection: systematic review and meta-analysis.to assess the usefulness of 2 rapid molecular diagnostic techniques, polymerase chain reaction (pcr) and loop-mediated isothermal amplification (lamp), in clostridium difficile infection (cdi).201222766084
gastric acid suppression and outcomes in clostridium difficile infection: a population-based study.to evaluate the association of gastric acid suppression medications, including proton pump inhibitors and histamine type 2 blockers, with outcomes in patients with clostridium difficile infection (cdi) in a population-based cohort.201222766083
synthesis and antibacterial activity against clostridium difficile of novel demethylvancomycin derivatives.to explore the structure-activity relationships (sar) of demethylvancomycin (2) and find more effective new chemical entities than known glycopeptides for the treatment of clostridium difficile (c. difficile), 17 novel n-substituted (n-arylmethylene or -aliphatic substituents) demethylvancomycin derivatives were prepared. these analogues have been evaluated in vitro for their antibacterial activities against c. difficile and enterococcus faecium (e. faecium). compounds 5d, 5h, and 5i with n-aryl ...201222765891
how much do ppis contribute to c. difficile infections?two separate systematic reviews and meta-analyses published in this edition of the american journal of gastroenterology conclude that proton pump inhibitor (ppi) use is associated with an ~70% increase in the risk of clostridium difficile infection (cdi). the two reviews employed different methodology but reached very similar conclusions. however, since the quality of evidence from the individual studies that were included in these analyses is relatively weak, their conclusions must be interpret ...201222764024
fighting fire with fire: is it time to use probiotics to manage pathogenic bacterial diseases?probiotics, when considered in clinical practice, have traditionally been used for prophylaxis; however, there is growing data suggesting treatment benefits in numerous disease states. in this review, we focus on probiotics as treatment for and prevention of several acute and chronic infectious processes including helicobacter pylori, clostridium difficile, necrotizing enterocolitis, ventilator-associated pneumonia, vancomycin-resistant enterococci, and nonalcoholic fatty liver disease. it is in ...201222763792
constipation in clostridium difficile infection.a patient presented to our hospital with worsening shortness of breath, cough and respiratory distress that slowly worsened over 7-10 days. she had a viral-like illness with runny nose and cough for 1 week, which became productive of yellowish sputum. she was treated with antibiotic and steroid with clinical improvement. her leucocyte count continued to increase despite discontinuation of both antibiotic and steroid. all culture results returned negative. she did not have any abdominal pain or d ...201222761206
evaluation of a new molecular test, the bd max cdiff, for detection of toxigenic clostridium difficile in fecal samples.a new molecular assay detecting toxigenic clostridium difficile, the bd max cdiff (becton, dickinson), was evaluated with 360 diarrheal feces samples. it exhibited high sensitivity (97.7%) and specificity (99.7%). the positive (97.7%) and negative (99.7%) predictive values of this test allow an accurate answer within 2 h.201222760042
the antimicrobial peptide cathelicidin modulates clostridium difficile-associated colitis and toxin a-mediated enteritis in mice.clostridium difficile mediates intestinal inflammation by releasing toxin a (txa), a potent enterotoxin. cathelicidins (camp as gene name, ll-37 peptide in humans and mcramp peptide in mice) are antibacterial peptides that also posses anti-inflammatory properties.201322760006
in silico analysis of sequenced strains of clostridium difficile reveals a related set of conjugative transposons carrying a variety of accessory genes.the human gut pathogen clostridium difficile contains many conjugative transposons that have an array of accessory genes. in the current study, recently sequenced genomes were analyzed to identify new putative conjugative transposons. eleven new elements in 5 c. difficile strains were identified and all had a similar structure to the previously described elements ctn1, ctn5 and ctn7 in c. difficile strain 630. each element identified did however contain a new set of accessory genes compared with ...201222754747
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
burden of clostridium difficile on the healthcare system.there are few high-quality studies of the costs of clostridium difficile infection (cdi), and the majority of studies focus on the costs of cdi in acute-care facilities. analysis of the best available data, from 2008, indicates that cdi may have resulted in $4.8 billion in excess costs in us acute-care facilities. other areas of cdi-attributable excess costs that need to be investigated are costs of increased discharges to long-term care facilities, of cdi with onset in long-term care facilities ...201222752870
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
current state of clostridium difficile treatment options.recent reports of reduced response to standard therapies for clostridium difficile infection (cdi) and the risk for recurrent cdi that is common with all currently available treatment agents have posed a significant challenge to clinicians. current recommendations include metronidazole for treatment of mild to moderate cdi and vancomycin for severe cdi. results from small clinical trials suggest that nitazoxanide and teicoplanin may be alternative options to standard therapies, whereas rifaximin ...201222752868
current status of clostridium difficile infection epidemiology.the dramatic changes in the epidemiology of clostridium difficile infection (cdi) during recent years, with increases in incidence and severity of disease in several countries, have made cdi a global public health challenge. increases in cdi incidence have been largely attributed to the emergence of a previously rare and more virulent strain, bi/nap1/027. increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settin ...201222752867
fidaxomicin inhibits spore production in clostridium difficile.fidaxomicin (fdx) is a novel antimicrobial agent with narrow-spectrum and potent bactericidal activity against clostridium difficile. in recent clinical trials, fdx was superior to vancomycin in preventing recurrences of c. difficile infection. a possible mechanism of reducing recurrence may be through an inhibitory effect on sporulation. the effect of fdx and its major metabolite, op-1118, on c. difficile growth and sporulation kinetics was compared with that of vancomycin, metronidazole, and r ...201222752866
treatment of first recurrence of clostridium difficile infection: fidaxomicin versus vancomycin.recurrence of clostridium difficile infection (cdi) occurs in approximately 25% of successfully treated patients. two phase 3 randomized, double-blind trials were conducted at 154 sites in the united states, canada, and europe to compare fidaxomicin vs vancomycin in treating cdi. patients with cdi received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days. the primary end point was clinical cure of cdi at end of treatment, and a secondary end point was recurrence duri ...201222752865
renal failure and leukocytosis are predictors of a complicated course of clostridium difficile infection if measured on day of diagnosis.nonsevere clostridium difficile infection (cdi) and severe cdi, which carries a higher risk than nonsevere cdi for treatment failure and cdi recurrence, are difficult to distinguish at the time of diagnosis. to investigate the prognostic value of 3 markers of severe cdi suggested by recent guidelines (fever, leukocytosis, and renal failure), we used the database of 2 randomized controlled trials, which contained information for 1105 patients with cdi. leukocytosis (risk ratio [rr], 2.29; 95% con ...201222752864
antimicrobial activities of fidaxomicin.fidaxomicin is bactericidal against clostridium difficile. the combined results of 8 in vitro studies of 1323 c. difficile isolates showed the minimum inhibitory concentration (mic) range of fidaxomicin to be ≤ 0.001-1 μg/ml, with a maximum mic for inhibition of 90% of organisms (mic(90)) of 0.5 μg/ml. isolates from 2 phase iii clinical trials demonstrated that fidaxomicin mics of baseline isolates did not predict clinical cure, failure, or recurrence of c. difficile infections. no resistance to ...201222752863
fidaxomicin preserves the intestinal microbiome during and after treatment of clostridium difficile infection (cdi) and reduces both toxin reexpression and recurrence of cdi.the microflora-sparing properties of fidaxomicin were examined during the conduct of a randomized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of clostridium difficile infection (cdi). fecal samples were obtained from 89 patients (45 received fidaxomicin, and 44 received vancomycin) at study entry and on days 4, 10, 14, 21, 28, and 38 for quantitative cultures for c. difficile and cytotoxin b fecal filtrate concentrat ...201222752862
fidaxomicin is an inhibitor of the initiation of bacterial rna synthesis.fidaxomicin was recently approved for the treatment of clostridium difficile infection. it inhibits transcription by bacterial rna polymerase. because transcription is a multistep process, experiments were conducted in which fidaxomicin was added at different stages of transcriptional initiation to identify the blocked step. dna footprinting experiments were also conducted to further elucidate the stage inhibited. fidaxomicin blocks initiation only if added before the formation of the "open prom ...201222752861
reduced acquisition and overgrowth of vancomycin-resistant enterococci and candida species in patients treated with fidaxomicin versus vancomycin for clostridium difficile infection.fidaxomicin causes less disruption of anaerobic microbiota during treatment of clostridium difficile infection (cdi) than vancomycin and has activity against many vancomycin-resistant enterococci (vre). in conjunction with a multicenter randomized trial of fidaxomicin versus vancomycin for cdi treatment, we tested the hypothesis that fidaxomicin promotes vre and candida species colonization less than vancomycin. stool was cultured for vre and candida species before and after therapy. for patient ...201222752860
fidaxomicin attains high fecal concentrations with minimal plasma concentrations following oral administration in patients with clostridium difficile infection.fidaxomicin has recently been approved for the treatment of clostridium difficile infection (cdi). as part of phase iii studies, plasma and fecal samples were analyzed for concentrations of fidaxomicin and its metabolite, op-1118. plasma samples were collected before and after dose receipt on the first and last days of therapy, and fecal samples were collected on the last day of therapy. samples were analyzed for fidaxomicin and op-1118 (metabolite), using validated liquid chromatography/tandem ...201222752859
safety analysis of fidaxomicin in comparison with oral vancomycin for clostridium difficile infections.fidaxomicin is a novel macrocyclic antibiotic recently approved by the us food and drug administration for the treatment of clostridium difficile-associated diarrhea in adults. we reviewed safety data from nonclinical studies and clinical trials (phases 1, 2a, and 3) with fidaxomicin. in nonclinical studies, fidaxomicin was administered orally at approximately 1 g/kg/d to dogs for up to 3 months with no significant target-organ toxicities observed. a total of 728 adults have received oral fidaxo ...201222752858
relapse versus reinfection: recurrent clostridium difficile infection following treatment with fidaxomicin or vancomycin.our study sought to compare the strain types of clostridium difficile causing initial and recurrent episodes of c. difficile infection (cdi) in adult patients with a first episode of cdi or 1 prior episode of cdi within the previous 90 days. strains originated from patients who had been entered into two phase 3 randomized clinical trials of fidaxomicin versus vancomycin. isolates of c. difficile from the initial and recurrent episodes within 28 (± 2) days of cure of cdi were compared using restr ...201222752857
the potential economic value of screening hospital admissions for clostridium difficile.asymptomatic clostridium difficile carriage has a prevalence reported as high as 51-85 %; with up to 84 % of incident hospital-acquired infections linked to carriers. accurately identifying carriers may limit the spread of clostridium difficile. since new technology adoption depends heavily on its economic value, we developed an analytic simulation model to determine the cost-effectiveness screening hospital admissions for clostridium difficile from the hospital and third party payer perspective ...201222752150
clostridium difficile infection in a patient with crohn disease.crohn disease is a chronic inflammatory disorder, which is rare in pediatric patients. the definite etiology and mechanism to induce an acute exacerbation of crohn disease remains mostly unknown. the authors report on a 14-year-old girl with crohn disease who has acute gastrointestinal symptoms caused by toxin a-producing clostridium difficile, which mimicked a flare-up of crohn disease. there was no preceding antibiotic prescription before the episode. the disease activity did not improve after ...201222748626
presence and molecular characterization of clostridium difficile and clostridium perfringens in intestinal compartments of healthy horses.clostridium difficile and clostridium perfringens are commonly associated with colitis in equids, but healthy carriers exist. scarce information is available on the prevalence of clostridium spp. in gastrointestinal compartments other than faeces in healthy horses, and it is unknown whether faecal samples are representative of proximal compartments. the objectives were to investigate the prevalence of c. difficile and c. perfringens in different intestinal compartments of healthy adult horses an ...201222748233
analysis of a clostridium difficile pcr ribotype 078 100 kilobase island reveals the presence of a novel transposon, tn6164.clostridium difficile is the main cause of antibiotic associated diarrhea. in the past decade, the number of c. difficile patients has increased dramatically, coinciding with the emergence of two pcr ribotypes 027 and 078. pcr ribotype 078 is also frequently found during c. difficile outbreaks in pigfarms. previously, the genome of the pcr ribotype 078 strain m120, a human isolate, was described to contain a unique insert of 100 kilobases.201222747711
the structure of clostridium difficile toxin a glucosyltransferase domain bound to mn2+ and udp provides insights into glucosyltransferase activity and product release.clostridiumdifficile toxin a (tcda) is a member of the large clostridial toxin family, and is responsible, together with c. difficile toxin b (tcdb), for many clinical symptoms d ring human infections. like other large clostridial toxins, tcda catalyzes the glucosylation of gtpases, and is able to inactivate small gtpases within the host cell. here, we report the crystal structures of the tcda glucosyltransferase domain (tcda-gt) in the apo form and in the presence of mn(2+) and hydrolyzed udp-g ...201222747490
application of copper to prevent and control infection. where are we now?the antimicrobial effect of copper has long been recognized and has a potential application in the healthcare setting as a mechanism to reduce environmental contamination and thus prevent healthcare-associated infection (hcai).201222738611
mbx-500, a hybrid antibiotic with in vitro and in vivo efficacy against toxigenic clostridium difficile.clostridium difficile infection (cdi) causes moderate to severe disease, resulting in diarrhea and pseudomembranous colitis. cdi is difficult to treat due to production of inflammation-inducing toxins, resistance development, and high probability of recurrence. only two antibiotics are approved for the treatment of cdi, and the pipeline for therapeutic agents contains few new drugs. mbx-500 is a hybrid antibacterial, composed of an anilinouracil dna polymerase inhibitor linked to a fluoroquinolo ...201222733075
protection against clostridium difficile infection with broadly neutralizing antitoxin monoclonal antibodies.the spore-forming bacterium clostridium difficile represents the principal cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. c. difficile infection (cdi) is mediated by 2 bacterial toxins, a and b; neutralizing these toxins with monoclonal antibodies (mabs) provides a potential nonantibiotic strategy for combating the rising prevalence, severity, and recurrence of cdi. novel antitoxin mabs were generated in mice and were humanized. the humanized antitoxin a mab pa-50 an ...201222732923
clinical risk factors for clostridium difficile-associated diseases.many factors appear to influence the chance of acquiring clostridium difficile (c. difficile) infection, and an accurate identification of risk factors could be beneficial in many ways. thus, in the present study, clinical risk factors for c. difficile-associated disease (cdad) in korea were identified. a total of 93 patients who met the inclusion criteria and 186 age/gender/ward/admission period-matched control patients were included in this study. statistically significant associations were fo ...201722729193
risk factors for mortality in clostridium difficile infection in the general hospital population: a systematic review.clostridium difficile infection (cdi) is one of the most important healthcare-associated infections, causing considerable mortality. numerous severity scores have been proposed to identify patients with cdi at risk of mortality, but a systematic review of the evidence upon which these are based has never been published. such a review could permit future development of scores that better predict mortality.201222727824
association of clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 nationwide inpatient sample database.diarrhea is a frequent and potentially severe complication in solid organ transplant (sot) recipients. one of the most common infectious etiologies of diarrhea in these patients is clostridium difficile. our objective was to investigate the association of c. difficile infection (cdi) with the outcomes of hospitalized sot patients.201222726461
conservative surgical treatment for toxic megacolon due to clostridium difficile infection in a transplanted pediatric patient.severe disease caused by clostridium difficile is frequently encountered in transplant recipients and carries a high mortality. numerous studies have been published on this subject in the adult population, but few in the pediatric setting. a 4-year-old boy who had undergone heart transplant 20 months earlier was admitted to the pediatric intensive care unit after humoral rejection. seven days after admission, he developed septic shock, abdominal distension, and paralytic ileus without diarrhea. ...201222726419
effectiveness of a short (4 day) course of oritavancin in the treatment of simulated clostridium difficile infection using a human gut model.we previously demonstrated that 7 days of oritavancin instillation effectively treats clostridium difficile infection (cdi) in a human gut model. oritavancin may be more effective than vancomycin due to apparently increased activity against spores. we compared the efficacy of shortened dosing duration (4 days) of oritavancin and vancomycin for cdi treatment using the gut model.201222723601
implementation of an antimicrobial stewardship program in a rural hospital.the implementation of a pharmacy-directed antimicrobial stewardship (ams) program involving the use of telemedicine technology is described.201222722593
prediction and prevention of upper gastrointestinal bleeding after cardiac surgery: a case control study.gastrointestinal (gi) complications of cardiovascular surgery, particularly bleeding, occur frequently.201222720275
evolution of testing algorithms at a university hospital for detection of clostridium difficile infections.we present the evolution of testing algorithms at our institution in which the c. diff quik chek complete immunochromatographic cartridge assay determines the presence of both glutamate dehydrogenase and clostridium difficile toxins a and b as a primary screen for c. difficile infection and indeterminate results (glutamate dehydrogenase positive, toxin a and b negative) are confirmed by the genexpert c. difficile pcr assay. this two-step algorithm is a cost-effective method for highly sensitive ...201222718938
probiotics for the prevention and treatment of clostridium difficile in older patients.clostridium difficile infection (cdi) is the leading cause of nosocomial diarrhoea in older people, causing substantial morbidity and mortality. the fact that cdi is almost exclusively a disease of older people and the debilitated indicates that patient susceptibility is a major determinant of who gets cdi. it would help efforts to combat this disease if we better understood and could reduce patient susceptibility. in this regard, several strategies are currently under investigation. the use of ...201222718155
recurrent clostridium difficile colitis in cystic fibrosis: an emerging problem.to examine the incidence of recurrent clostridium difficile infection in patients with cystic fibrosis (cf), including patients who had undergone lung transplantation, and review clinical findings in hospitalized patients with c. difficile colitis.201322717532
incidence and clinical features of clostridium difficile infection in korea: a nationwide study.the incidence and severity of clostridium difficile infections (cdi) have increased in western countries. however, there are limited data regarding the epidemiology of cdi in eastern countries. this nationwide study was conducted in 17 hospitals to determine temporal trends in cdi incidence (from 2004 to 2008) in south korea. the total incidence of cdi in korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (p = 0·028). when analysing the clinical features of 1367 cdi pa ...201322717061
moxifloxacin safety: an analysis of 14 years of clinical data.moxifloxacin, a fluoroquinolone antibiotic, is used for the treatment of respiratory tract, pelvic inflammatory disease, skin, and intra-abdominal infections. its safety profile is considered favorable in most reviews but has been challenged with respect to rare but potentially fatal toxicities (e.g. hepatic, cardiac, or skin reactions).201222715866
epidemiology of clostridium difficile infections in a tertiary-care hospital in korea.to survey healthcare-associated clostridium difficile infection (ha-cdi) in a 900-bed tertiary-care hospital, we prospectively investigated the epidemiology of cdi and distribution of pcr-ribotypes. from february 2009 through january 2010, all patients with ha-cdi were enrolled. epidemiological information and prescription records for antibiotics were collected. the c. difficile isolates were characterized using reference strains and were tested for antibiotic susceptibility. during the survey, ...201322712697
clostridium difficile infection: managing the risks. 201222712142
clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis.clostridium difficile-associated diarrhea (cdad) is a major cause of morbidity and increasing health-care costs among hospitalized patients. although exposure to antibiotics remains the most documented risk factor for cdad, attention has recently been directed toward a plausible link with proton pump inhibitors (ppis). however, the results of studies on the association between cdad and ppis remain controversial. we have conducted a meta-analysis to summarize the association between ppis and cdad ...201222710578
high prevalence and resistance rates to antibiotics in anaerobic bacteria in specimens from patients with chronic balanitis.aim of the study was to assess both prevalence and antibiotic resistance in anaerobic bacteria from glans penis skin of 70 adults. strain susceptibility was determined by breakpoint susceptibility test or e test. in 9 asymptomatic, 48 untreated and 13 treated symptomatic patients, anaerobes were found in 22.2%, 70.8% and 53.3%, respectively. gram-positive strains (gpas) were 2.2-fold more common than gram-negative ones. prevalent gram-negative (gnas) and gpas were prevotella spp. and anaerobic c ...201222710106
changing antibiotic prophylaxis for primary joint arthroplasty affects postoperative complication rates and bacterial spectrum.the reduction of clostridium difficile associated diarrhoea (cdad) is a national priority. as part of the c. difficile improvement plan in our trust, antibiotic prophylaxis for primary arthroplasty was changed from cefuroxime to gentamicin. gentamicin was chosen following a review of the sensitivity profiles of all the organisms isolated from infected primary arthoplasties.201322709532
fidaxomicin for clostridium difficile-associated diarrhoea: epidemiological method for estimation of warranted price.fidaxomicin is a macrocyclic antibiotic approved in 2011 by the us food and drug administration for treatment of clostridium difficile-associated diarrhoea (cdad).201222708825
[clostridium difficile infection in children--experience of clinical centre in bydgoszcz].clostridium difficile (cd) is one of the main factors of nosocomial infections both in children and adults and the number these infections is still growing. there is an increasing number of community-associated cdad and cdis with no exposure to antibiotics. tests for cd among children are not routinely conducted because of high rate of carrying (from 13 to 70% infants). the objective of a study was to assess the frequency cdi among children with diarrhea, analysis of the risk factors of cdi and ...201222708301
[clostridium difficile as etiological agent of pseudomembranous colitis]. 201222708300
evaluation of three enzyme immunoassays and a loop-mediated isothermal amplification test for the laboratory diagnosis of clostridium difficile infection.the laboratory diagnosis of clostridium difficile infection (cdi) consists of the detection of toxigenic clostridium difficile, and/or its toxins a or b in stool preferably in a two-step algorithm. in a prospective study, we compared the performance of three toxin enzyme immunoassays (eias)-immunocard toxins a & b, premier toxins a & b and c. diff quik chek complete, which combines a toxins test and a glutamate dehydrogenase (gdh) antigen eia in one device -and the loop-mediated isothermal ampli ...201222706512
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