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efficacy of lff571 in a hamster model of clostridium difficile infection.lff571 is a novel semisynthetic thiopeptide antibiotic with potent activity against a variety of gram-positive pathogens, including clostridium difficile. in vivo efficacy of lff571 was compared to vancomycin in a hamster model of c. difficile infection (cdi). infection was induced in golden syrian hamsters using a toxigenic strain of c. difficile. treatment started 24 h postinfection and consisted of saline, vancomycin, or lff571. cox regression was used to analyze survival data from a cohort o ...201222644020
mechanism of action of and mechanism of reduced susceptibility to the novel anti-clostridium difficile compound lff571.lff571 is a novel semisynthetic thiopeptide and potent inhibitor of gram-positive bacteria. we report that the antibacterial activity of lff571 against clostridium difficile is due to inhibition of translation. single-step mutants of c. difficile with reduced susceptibility to lff571 were selected at frequencies of <4.5 × 10(-11) to 1.2 × 10(-9). sequencing revealed a g260e substitution in the thiopeptide-binding pocket of elongation factor tu. importantly, this mutation did not confer cross-res ...201222644023
identification of ligand analogues that control c-di-gmp riboswitches.riboswitches for the bacterial second messenger c-di-gmp control the expression of genes involved in numerous cellular processes such as virulence, competence, biofilm formation, and flagella synthesis. therefore, the two known c-di-gmp riboswitch classes represent promising targets for developing novel modulators of bacterial physiology. here, we examine the binding characteristics of circular and linear c-di-gmp analogues for representatives of both class i and ii c-di-gmp riboswitches derived ...201222646696
clostridium difficile. a super serious bug. 201222649818
the value of repeat clostridium difficile toxin testing during and after an outbreak of c difficile-associated diarrhea.the recent increase in clostridium difficile-associated diarrhea (cdad) has led to questions about the reproducibility and sensitivity of c difficile toxin testing (cdtt). while there have been recommendations to repeat cdtt following a negative result, previous studies have failed to show a benefit. however, no studies were performed during an outbreak of cdad. the value of repeat cdtt after an initial negative result in patients tested during and after an outbreak of cdad is reported in the pr ...201122654928
clostridium difficile and entamoeba histolytica infections in patients with colitis in the philippines.amoebiasis is a common cause of non-specific colitis in the philippines. the prevalence of clostridium difficile infection with colitis is unknown. empiric use of metronidazole for colitis treatment is widely practiced. we investigated the association of c. difficile or entamoeba histolytica infection with endoscopically/histopathologically proven colitis among adults in the philippines. two hundred and ten patients undergoing colonoscopy were enrolled. demographic and clinical data were reviewe ...201222657531
clinical negligence, litigation and healthcare-associated infections.litigation costs resulting from clinical negligence claims involving healthcare-associated infections are a significant but underappreciated cost to healthcare organizations. in england these claims are handled on behalf of the national health service (nhs) organizations by the nhs litigation authority (nhsla). the total number of claims and the amounts awarded have increased significantly in recent years.201222658237
antimicrobial susceptibility testing of clostridium difficile using eucast epidemiological cut-off values and disk diffusion correlates.with the emergence of reduced susceptibility of clostridium difficile to metronidazole and vancomycin the value of antimicrobial susceptibility testing has increased. the aim of our study was to evaluate disk diffusion for susceptibility testing of c. difficile by comparing disk diffusion results with mics from gradient tests and to propose zone diameter breakpoint correlates for the eucast epidemiological cut-off values (ecoffs) recently published. we tested 211 clinical isolates of c. difficil ...201222672504
[intrahospital mortality in patients with clostridium difficile-associated diarrhea infection].clostridium difficile (c. difficile) is a gram-positive anaerobic bacillus capable of producing diarrhea or colitis in the hospitalized patient, particularly in those exposed to the use of antibiotics, and 6% to 38% mortality in patients with c. difficile-associated diarrhea (cdad) has been described.201222672850
[clostridium difficile-associated diarrhea infection: is it time for us to start worrying in mexico?]. 201222672852
successful use of nitazoxanide in the treatment of recurrent clostridium difficile infection.a 78-year-old, retired caucasian male presented in emergency room with 3 days history of progressive watery diarrhoea. two weeks earlier, he received intravenous levofloxacin for community acquired pneumonia. the patient was diagnosed as severe clostridium difficile infection based on clinical presentation, labs and imaging studies. the patient was initially treated with intravenous metronidazole and oral vancomycin. while awaiting subacute rehabilitation placement, the patient relapsed twice. a ...201122674696
a pilot study of rapid benchtop sequencing of staphylococcus aureus and clostridium difficile for outbreak detection and surveillance.to investigate the prospects of newly available benchtop sequencers to provide rapid whole-genome data in routine clinical practice. next-generation sequencing has the potential to resolve uncertainties surrounding the route and timing of person-to-person transmission of healthcare-associated infection, which has been a major impediment to optimal management.201222674929
automated detection of toxigenic clostridium difficile in clinical samples: isothermal tcdb amplification coupled to array-based detection.clostridium difficile can carry a genetically variable pathogenicity locus (paloc), which encodes clostridial toxins a and b. in hospitals and in the community at large, this organism is increasingly identified as a pathogen. to develop a diagnostic test that combines the strengths of immunoassays (cost) and dna amplification assays (sensitivity/specificity), we targeted a genetically stable paloc region, amplifying tcdb sequences and detecting them by hybridization capture. the assay employs a ...201222675134
fecal transplantation for the treatment of clostridium difficile infection. 201222675283
in vitro evaluation of single- and multi-strain probiotics: inter-species inhibition between probiotic strains, and inhibition of pathogens.many studies comparing the effects of single- and multi-strain probiotics on pathogen inhibition compare treatments with different concentrations. they also do not examine the possibility of inhibition between probiotic strains with a mixture. we tested the ability of 14 single-species probiotics to inhibit each other using a cross-streak assay, and agar spot test. we then tested the ability of 15 single-species probiotics and 5 probiotic mixtures to inhibit clostridium difficile, escherichia co ...201222677262
vermin on pig farms are vectors for clostridium difficile pcr ribotypes 078 and 045.clostridium difficile is a gram positive, spore forming, toxin producing, anaerobic bacteria and an opportunistic pathogen for man and many animal species, causing diarrhea in young piglets. piglets probably become colonized from the environment. to investigate the possible spread and transmission of c. difficile by vermin, vermin samples were collected on a pig farm in the netherlands and investigated for the presence of c. difficile. samples of house mice (n=53), drain flies (n=39), lesser hou ...201222682200
clostridium difficile: development of a novel candidate vaccine.clostridium difficile has become the most frequent hospital-acquired infection in north america and the eu. c. difficile infection (cdi) is present worldwide and disease awareness is increasing. in the us, eu, and canada, in addition to hospital diagnosed disease, cdi has also been reported with increasing frequency in the community. hypervirulent strains have increased the morbidity and mortality associated with cdi. current treatment options are suboptimal. of all patients treated for cdi, 20% ...201222682287
a year in review: new drugs for older adults in 2011.new drugs approved by the food and drug administration (fda) may offer tremendous clinical advances by providing health care providers with new treatment strategies. however, additional care must be taken for safe and effective use of these new agents by older adults.201222682643
fda drug safety communications: a narrative review and clinical considerations for older adults.the us food and drug administration (fda) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. this has resulted in an increase in communication from the fda in recent years about the safety profile of certain drugs. it is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public.201222683398
secretion of clostridium difficile toxins a and b requires the holin-like protein tcde.the pathogenesis of clostridium difficile, the major cause of antibiotic-associated diarrhea, is mainly associated with the production and activities of two major toxins. in many bacteria, toxins are released into the extracellular environment via the general secretion pathways. c. difficile toxins a and b have no export signature and their secretion is not explainable by cell lysis, suggesting that they might be secreted by an unusual mechanism. the tcde protein encoded within the c. difficile ...201222685398
incidence of clostridium difficile infection in children with inflammatory bowel disease compared to oncology and immunocompetent patients.the aim of this study was to determine the incidence of clostridium difficile infection in hospitalized children with inflammatory bowel disease (ibd) and to compare it to other immunosuppressed patients at risk (oncology patients) as well as to immunocompetent patients.201222688504
critical role for myd88-mediated neutrophil recruitment during clostridium difficile colitis.clostridium difficile can infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. little is known about the innate immune signaling pathways that marshal inflammatory responses to c. difficile infection and whether protective and pathogenic inflammatory responses can be dissociated. toll-like receptors predominantly signal via the myd88 adaptor protein and are important mediators of innate immune signaling in the intestinal muco ...201222689818
chemotherapy patients with c. difficile colitis have outcomes similar to immunocompetent c. difficile patients.clostridium difficile colitis (cdc) patients receiving chemotherapy for hematologic malignancies are anticipated to have worse outcomes than immunocompetent cdc patients.201222692587
comparison of two capillary gel electrophoresis systems for clostridium difficile ribotyping, using a panel of ribotype 027 isolates and whole-genome sequences as a reference standard.pcr ribotyping is the most commonly used clostridium difficile genotyping method, but its utility is limited by lack of standardization. in this study, we analyzed four published whole genomes and tested an international collection of 21 well-characterized c. difficile ribotype 027 isolates as the basis for comparison of two capillary gel electrophoresis (cge)-based ribotyping methods. there were unexpected differences between the 16s-23s rrna intergenic spacer region (isr) allelic profiles of t ...201222692737
how a bowel tumour led to meningitis.this report summarises a case history in which a 75-year-old man was admitted with bacterial meningitis caused by streptococcus bovis. a subsequent abdominal investigation in the light of the known association between invasive s bovis infection and colonic cancer confirmed the suspicion of a cancer located to the rectum. the patient died from clostridium difficile enterocolitis with sepsis and multi-organ failure. this is a highly relevant and interesting case presentation, which besides providi ...201122692778
clostridium difficile infection in humans and piglets: a 'one health' opportunity.clostridium difficile causes infectious diarrhoea in humans and animals. it has been found in both diarrhoeal and non-diarrhoeal pigs, horses and cattle, suggesting a potential reservoir for human insection, and in 20-40 % of meat products in canada and the usa, suggesting the possibility, albeit not proven, of food-borne transmission. although it is not yet completely clear, it is likely that excessive antimicrobial exposure is driving the establishment of c. difficile in animals, in a manner a ...201322695920
implementation of standardised surveillance for clostridium difficile infections in australia: initial report from the victorian healthcare associated infection surveillance system.detection of a hypervirulent strain of clostridium difficile in victoria led to commencement of targeted surveillance for c. difficile infection in 2010. cases were reported through the victorian healthcare associated infection surveillance system. between 1 october 2010 and 31 march 2011, 477 cases of c. difficile infection were identified; 11 (2.3%) secondary to a hypervirulent strain. three hundred and seventy (1.7 per 10,000 occupied bed days) were healthcare associated. data reflect success ...201222697155
nosocomial diarrhea: evaluation and treatment of causes other than clostridium difficile.diarrhea is common among hospitalized patients but the causes are distinct from those of diarrhea in the community. we review existing data about the epidemiology of nosocomial diarrhea and summarize recent progress in understanding the mechanisms of diarrhea. clinicians should recognize that most cases of nosocomial diarrhea have a noninfectious etiology, including medications, underlying illness, and enteral feeding. apart from clostridium difficile, the frequency of infectious causes such as ...201222700831
diarrhea etiology in a pediatric emergency department: a case control study.the etiology of childhood diarrhea is frequently unknown.201222700832
inappropriate use of gastric acid suppression therapy in hospitalized patients with clostridium difficile-associated diarrhea: a ten-year retrospective analysis.purpose. the incidence of clostridium difficile-associated diarrhea (cdad) has steadily increased over the past decade. a multitude of factors for this rise in incidence of cdad have been postulated, including the increased use of gastric acid suppression therapy (gast). despite the presence of practice guidelines for use of gast, studies have demonstrated widespread inappropriate use of gast in hospitalized patients. we performed a retrospective analysis of inpatients with cdad, with special em ...201222701180
efficacy and safety of fidaxomicin compared with oral vancomycin for the treatment of adults with clostridium difficile-associated diarrhea: data from the opt-80-003 and opt-80-004 studies.clostridium difficile is emerging as one of the most important and devastating pathogens affecting hospitalized populations around the world. the incidence of c. difficile infection is increasing and disease severity is worsening. thus, an effective alternative to metronidazole and oral vancomycin is urgently needed. two phase iii trials, opt-80-003 and opt-80-004, showed that oral fidaxomicin for 10 days was noninferior compared with treatment with oral vancomycin among adult patients with toxi ...201222702523
you can teach old pathogens new tricks: the zoonotic potential of escherichia coli, clostridium difficile, staphylococcus aureus, and enterococci, or from noah's ark to pandora's box. 201222703445
comparative analysis of an expanded clostridium difficile reference strain collection reveals genetic diversity and evolution through six lineages.clostridium difficile is an anaerobic bacillus that resides in the gut and has rapidly emerged as a leading cause of antibiotic associated diarrheal disease in humans. the genetic basis of the pathogenicity of c. difficile remains poorly understood. in this study we aimed at characterizing the genetic diversity of c. difficile strains by three different methods (pcr ribotyping, multilocus sequence typing and genetic markers) to improve the typing of c. difficile. our study was performed on a ref ...201222705462
prophage carriage and diversity within clinically relevant strains of clostridium difficile.prophages are encoded in most genomes of sequenced clostridium difficile strains. they are key components of the mobile genetic elements and, as such, are likely to influence the biology of their host strains. the majority of these phages are not amenable to propagation, and therefore the development of a molecular marker is a useful tool with which to establish the extent and diversity of c. difficile prophage carriage within clinical strains. to design markers, several candidate genes were ana ...201222706062
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
[clostridium difficile as etiological agent of pseudomembranous colitis]. 201222708300
[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
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
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
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
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
clostridium difficile infection: managing the risks. 201222712142
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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