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[steroid-resistant nephrotic syndrome complicated with severe streptococcus pneumonlae peritonitis in a 10-year-old girl--case report].primary bacterial peritonitis is a rare complication of idiopathic nephrotic syndrome (ins) in children, found in 1.5-3.7% cases. the 10-year-old girl was admitted with ins relapse: generalized edema, proteinuria 630 mg/kg/24 h, hypoalbuminemia 1.8 g/dl, hypogammaglobulinemia 74.0 mg/dl (n: 618-1537 mg/dl), gfr 71.6 ml/min/1.73 m2. she was treated with prednisone 60 mg/24 h. on 5th day severe pain, fever, crp (15.5 mg/dl) and leukocytosis (19.5 tys/mm3) rise occurred. on 6th day due to suspicion ...201324490466
recurrence of clostridium difficile infection among veterans with spinal cord injury and disorder.recurrent clostridium difficile (cdi) infection is a growing concern; however, there are little data on impact of recurrent cdi on those with spinal cord injury and disorder (sci/d). therefore, the objective of this study was to identify risk factors associated with recurrence of cdi among veterans with sci/d.201424485372
severe clinical outcome is uncommon in clostridium difficile infection in children: a retrospective cohort study.clostridium difficile infection (cdi) is the most common cause of health care-associated diarrhea in children and adults. although serious complications of cdi have been reported to be increasing in adults, this trend has not yet been demonstrated in children. the purpose of this study was to examine the features of cdi in a pediatric population, with special attention to the occurrence of cdi-related severe outcomes.201424485120
biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) by recombinant escherichia coli expressing leucine metabolism-related enzymes derived from clostridium difficile.an obligate anaerobic bacterium clostridium difficile has a unique metabolic pathway to convert leucine to 4-methylvalerate, in which 4-methyl-2-pentenoyl-coa (4m2pe-coa) is an intermediate of this pathway. 4m2pe-coa is also able to be converted to 3-hydroxy-4-methylvalerate (3h4mv), a branched side chain monomer unit, for synthesis of polyhydroxyalkanoate (pha) copolymer. in this study, to synthesize 3h4mv-containing pha copolymer from leucine, the leucine metabolism-related enzymes (ldha and h ...201424484910
sequence similarity of clostridium difficile strains by analysis of conserved genes and genome content is reflected by their ribotype affiliation.pcr-ribotyping is a broadly used method for the classification of isolates of clostridium difficile, an emerging intestinal pathogen, causing infections with increased disease severity and incidence in several european and north american countries. we have now carried out clustering analysis with selected genes of numerous c. difficile strains as well as gene content comparisons of their genomes in order to broaden our view of the relatedness of strains assigned to different ribotypes. we analyz ...201424482682
lipoprotein cd0873 is a novel adhesin of clostridium difficile.clostridium difficile is a cause of antibiotic-associated diarrhea and colitis, a healthcare-associated intestinal disease. colonization of the gut is a critical step in the course of infection. the c. difficile lipoprotein cd0873 was identified as a putative adhesin through a bioinformatics approach. surface exposure of cd0873 was confirmed and a cd0873 mutant was generated. the cd0873 mutant showed a significant reduction in adherence to caco-2 cells and wild-type bacteria preincubated with an ...201424482399
a study in transfer learning: leveraging data from multiple hospitals to enhance hospital-specific predictions.data-driven risk stratification models built using data from a single hospital often have a paucity of training data. however, leveraging data from other hospitals can be challenging owing to institutional differences with patients and with data coding and capture.201524481703
[successful home-made fecal transplant for an elderly woman].recurrent clostridium difficile infection (cdi) is a challenge for infectious disease specialists. a third of first recurrences will fail antibiotic therapy. several mechanisms have been proposed to explain this, such as persistence of spores, inadequate antibody response, and altered gut microbiota. standard recommendations for cdi treatment include metronidazole and vancomycin. fecal transplant has proven to be an effective therapy for recurrent cdi. infusion of stools can be administered to t ...201424481438
prospects for flavonoid and related phytochemicals as nature-inspired treatments for clostridium difficile infection.there is a need for novel treatments for clostridium difficile infection(cdi). antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against cl. difficile. we explored their anti-difficile properties.201424479135
a cost-effective approach for detection of toxigenic clostridium difficile: toxigenic culture using chromid clostridium difficile agar.we evaluated the performance and the cost of toxigenic culture using a commercial chromogenic medium (cdif) for 538 stool specimens. compared with real-time pcr, this method was found to detect an additional 9% of positive specimens and result in 61% reduction in material costs, with a trade-off increase in turnaround time of 1 day.201424478510
impact of changes in clostridium difficile testing practices on stool rejection policies and c. difficile positivity rates across multiple laboratories in the united states.we describe the adoption of nucleic acid amplification tests (naat) for clostridium difficile diagnosis and their impact on stool rejection policies and c. difficile positivity rates. of the laboratories with complete surveys, 51 (43%) reported using naat in 2011. laboratories using naat had stricter rejection policies and increased positivity rates.201424478500
economic evaluation of laboratory testing strategies for hospital-associated clostridium difficile infection.clostridium difficile infection (cdi) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have cdi, their isolation while awaiting laboratory results is costly. newer rapid tests for cdi may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. we used decision analysis from the hospital perspective to compare multiple cdi testing algorithms for adult inpatients with suspected cdi, assuming patient m ...201424478478
protection from clostridium difficile infection in cd4 t cell- and polymeric immunoglobulin receptor-deficient mice.clostridium difficile rivals methicillin-resistant staphylococcus aureus as the primary hospital-acquired infection. c. difficile infection (cdi) caused by toxins a and/or b can manifest as mild diarrhea to life-threatening pseudomembranous colitis. although most patients recover fully from cdi, ~20% undergo recurrent disease. several studies have demonstrated a correlation between anti-toxin antibody (ab) and decreased recurrence; however, the contributions of the systemic and mucosal ab respon ...201424478068
colonic immunopathogenesis of clostridium difficile infections.there are major gaps in our understanding of the immunopathogenesis of clostridium difficile infections (cdis). in this study, 36 different biomarkers were examined in the stools of cdi and non-cdi patients using the proteome profiler human cytokine array assay and quantitative enzyme-linked immunosorbent assay. diarrheal stools from patients with cdi (cdi-positive diarrheal stools) showed higher relative amounts of the following inflammatory markers than the diarrheal stools from cdi-negative p ...201424477852
outcomes of clostridium difficile infection in recipients of solid abdominal organ transplants.knowledge of outcomes of clostridium difficile infection (cdi) in solid organ transplant (sot) recipients is limited. to evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with cdi at a single center over 14 yr. data pertaining to all episodes of cdi were collected. multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. overall, 170 patients developed 215 epis ...201424476412
transmission of clostridium difficile spores in isolation room environments and through hospital beds.the aim of this study was to determine the dissemination of clostridium difficile (cd) spores in a hospital setting where the potassium monopersulfate-based disinfectant virkon™ was used for cleaning. in the initial part of the study, we sampled 16 areas of frequent patient contact in 10 patient rooms where a patient with cd infection (cdi) had been accommodated. in the second part of the study, we obtained samples from 10 patient beds after discharge of cdi patients, both before and after the b ...201424475890
what does the talking?: quorum sensing signalling genes discovered in a bacteriophage genome.the transfer of novel genetic material into the genomes of bacterial viruses (phages) has been widely documented in several host-phage systems. bacterial genes are incorporated into the phage genome and, if retained, subsequently evolve within them. the expression of these phage genes can subvert or bolster bacterial processes, including altering bacterial pathogenicity. the phage phicdhm1 infects clostridium difficile, a pathogenic bacterium that causes nosocomial infections and is associated w ...201424475037
an interprofessional approach to reducing the overutilization of stress ulcer prophylaxis in adult medical and surgical intensive care units.overutilization of stress ulcer prophylaxis (sup) in the intensive care unit (icu) is common. acid-suppressive therapies routinely used for sup are best reserved for patients with greatest risk of clinically important bleeding as they have been associated with nosocomial pneumonia, clostridium difficile infection and increased hospital cost.201424473490
[screening for opportunistic infections and vaccination before introduction of biologic therapy].patients on anti-tnfalpha medications carry a higher risk for developing opportunistic infections. in order to introduce anti-tnfalpha therapy, screening for hepatitis viruses b and c, hiv, ebv, hpv, tbc, bacterial, fungal and parasitic infections should be performed. screening involves patient's history of earlier infectious diseases, vaccinations and traveling to parts of the world with endemic diseases. clinical examination should be supplemented with stomatologic and gynecologic exams. labor ...201324471299
fecal microbiota transplantation: the state of the art.clostridium difficile infection (cdi) is an emerging problem in terms of incidence, morbidity and mortality. currently available treatment options are not always effective, especially in cases of recurrent/refractory or complicated cdi. the gut microbiota transplantation is a technique that has been sporadically practiced since the '50s, but its clinical efficacy has only recently been supported by scientific evidence. in the present article, we report the pathophysiological basis and the clinic ...201324470963
diagnosis of clostridium difficile infection: comparison of four methods on specimens collected in cary-blair transport medium and tcdb pcr on fresh versus frozen samples.clostridium difficile infection (cdi) caused by toxigenic strains of c. difficile is primarily a nosocomial infection with increasing prevalence. stool specimens are typically collected in cary-blair transport medium to maximize culture-based detection of common stool pathogens. the goal of this study was to establish an analytically accurate and efficient algorithm for the detection of cdi in our patient population using samples collected in cary-blair transport medium. in addition, we wished t ...201124470904
mortality in hospitalized older adults associated with clostridium difficile infection at a district hospital.clostridium difficile is the most common cause of hospital acquired infectious diarrhea in the developed world and has re-emerged in recent years with apparent greater morbidity and mortality. despite this, there is little recent published data from the uk concerning associated mortality. we performed a case control study at a uk district general hospital of 66 hospitalized patients over the age of 65 years with c. difficile infection compared to 3-5 controls matched for age, sex and minimum len ...201024470889
clostridium difficile toxin cdt hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence.clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by the actions of rho-glucosylating toxins a and b. recently identified hypervirulent strains, which are associated with increased morbidity and mortality, additionally produce the actin-adp-ribosylating toxin c. difficile transferase (cdt). cdt depolymerizes actin, causes formation of microtubule-based protrusions, and increases pathogen adherence. here we show that cdt-induced protrusions allow vesicle tra ...201424469807
stool substitute transplant therapy for the eradication of clostridium difficile infection: 'repoopulating' the gut.fecal bacteriotherapy ('stool transplant') can be effective in treating recurrent clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent c. difficile infection that had failed repeated standard antibiotics. thirty-three isolates were recovered from a healthy donor stool sam ...201324467987
shedding of clostridium difficile pcr ribotype 078 by zoo animals, and report of an unstable metronidazole-resistant isolate from a zebra foal (equus quagga burchellii).clostridium difficile is an emerging and potentially zoonotic pathogen, but its prevalence in most animal species, including exhibition animals, is currently unknown. in this study we assessed the prevalence of faecal shedding of c. difficile by zoo animals, and determined the ribotype, toxin profile and antimicrobial susceptibility of recovered isolates. a total of 200 samples from 40 animal species (36.5% of which came from plains zebra, equus quagga burchellii) were analysed. c. difficile was ...201424467928
is there any value in measuring faecal calprotectin in clostridium difficile positive faecal samples?markers of intestinal inflammation have been proposed for inclusion in clostridium difficile diagnostic algorithms. faecal calprotectin (f-cp), a sensitive marker of intestinal inflammation, was evaluated for utility in c. difficile diagnosis in the hospital setting. one hundred and twenty c. difficile positive and 99 c. difficile negative faecal samples of hospital-acquired diarrhoea were analysed for f-cp using a quantitative elisa. c. difficile positivity was confirmed using elisas for either ...201424464697
clostridium difficile and cytomegalovirus colitis coinfection after bariatric surgery: case report. 201324463907
[cloudy peritoneal effluent and diarrhoea due to clostridium difficile]. 201424463873
severity assessment scores to guide empirical use of antibiotics in community acquired pneumonia.severity assessment scores were first developed to predict the 30 day mortality in community acquired pneumonia; however, several guidelines have extended their use to guide empirical antibiotic prescription decisions. this approach has theoretical advantages because a decrease in broad-spectrum antibiotic treatment in low-risk patients might reduce antibiotic-related side-effects, and to give broad-spectrum therapy to patients at higher risk of death is intuitive. however, evidence in support o ...201324461668
fulminant clostridium difficile colitis: prospective development of a risk scoring system.of the patients with a clostridium difficile infection, 2% to 8% will progress to fulminant c. difficile colitis (fcdc), which carries high morbidity and mortality. no system exists to rapidly identify patients at risk for developing fcdc and possibly in need of surgical intervention. our aim was to design a simple and accurate risk scoring system (rss) for daily clinical practice.201424458048
faecal transplantation for clostridium difficile infection. three cases treated in italy. 201424457126
a case of an acquired factor viii inhibitor complicated by multiple treatment-related opportunistic infections and review of the literature.this case report describes a patient with an idiopathic acquired factor viii inhibitor and severe bleeding. she was treated with rituximab after failing first-line treatment with steroids and cyclophosphamide. two months following rituximab treatment, our patient developed a succession of severe opportunistic infections requiring intensive care unit admission. over a period of 12 weeks she required treatment for pseudomonas aeruginosa septicaemia, herpes simplex gingivostomatitis and pharyngoton ...201324455336
metronidazole induced liver injury: a rare immune mediated drug reaction.drug induced liver injury (dili) can result either from dose-dependent direct hepatotoxicity or from an unpredictable dose-independent idiosyncratic reaction. incidence of idiosyncratic dili is estimated to be approximately 10-15 per 100,000 patient years. here we report an extremely rare case of metronidazole induced delayed immune-allergic hepatocellular liver injury masquerading as autoimmune hepatitis. a previously healthy 54-year-old caucasian male, who was treated with metronidazole for cl ...201324455335
real-time cellular analysis coupled with a specimen enrichment accurately detects and quantifies clostridium difficile toxins in stool.we describe here the use of an immunomagnetic separation enrichment process coupled with a modified real-time cellular analysis (rtca) system (rtca version 2) for the detection of c. difficile toxin (cdt) in stool. the limit of cdt detection by rtca version 2 was 0.12 ng/ml. among the consecutively collected 401 diarrheal stool specimens, 53 (13.2%) were toxin-producing c. difficile strains by quantitative toxigenic culture (qtc); bacterial loads ranged from 3.00 × 10(1) to 3.69 × 10(6) cfu/ml. ...201424452160
reductions in intestinal clostridiales precede the development of nosocomial clostridium difficile infection.antimicrobial use is thought to suppress the intestinal microbiota, thereby impairing colonization resistance and allowing clostridium difficile to infect the gut. additional risk factors such as proton-pump inhibitors may also alter the intestinal microbiota and predispose patients to clostridium difficile infection (cdi). this comparative metagenomic study investigates the relationship between epidemiologic exposures, intestinal bacterial populations and subsequent development of cdi in hospit ...201324450844
detection of nosocomial clostridium difficile infections with toxigenic strains despite negative toxin a and b testing on stool samples.a two-step diagnostic algorithm is recommended to detect clostridium difficile infections; however, samples are regularly found that are glutamate dehydrogenase (gdh) positive but stool toxin negative. in the present single-centre prospective study we focused on these 'difficult-to-interpret' samples and characterized them by anaerobic culture, toxigenic culture, slpa sequence typing and multiplex pcr (genotype cdiff). the majority of stool toxin a and b-negative samples have been caused by toxi ...201424450741
ribotype 027 clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality.we evaluated clinical and diagnostic indicators of severe c. difficile infection (cdi) and their association with poor clinical outcome. a total of 210 patients positive according to pcr (toxin b: tcdb) were included, with patients having a median age of 62 years and a charlson co-morbidity index (ci) score of 5. ninety-one percent (n = 191) were positive by toxigenic culture and 61% (n = 129) had stool toxin. toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g vers ...201424449345
a case study of a real-time evaluation of the risk of disease transmission associated with a failure to follow recommended sterilization procedures.failures to follow recommendations for reprocessing of surgical instruments may place patients at risk for exposure to pathogenic microorganisms. when such failures occur, medical facilities often face considerable uncertainty and challenges in assessing the actual risks of disease transmission.201424447336
comparative proteomic analysis of clostridium difficile isolates of varying virulence.the soluble proteome of three clostridium difficile strains of varying pathogenic potential, designated b-1, tra 5/5 and 027 sm, were compared using differential in-gel electrophoresis in which the proteins of each strain were labelled with cydyes. this enabled visual inspection of the 2d profiles of strains and identification of differentially expressed proteins using image analysis software. unlabelled protein reference maps of the predominant proteins were then generated for each strain using ...201424445512
antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to clostridium difficile infection.antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including clostridium difficile. here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to c. difficile infection. levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, r ...201424445449
a randomized trial of soap and water hand wash versus alcohol hand rub for removal of clostridium difficile spores from hands of patients. 201424442089
comparison of 3 severity criteria for clostridium difficile infection.effective severity criteria are needed to guide management of clostridium difficile infection (cdi). in this retrospective study, outcomes were compared between patients with mild-moderate versus severe cdi according to 3 different severity criteria: those included in the 2010 society for healthcare epidemiology of america/infectious diseases society of america guidelines, those from a recent clinical trial, and our hospital-specific guidelines.201424442086
fecal microbiota transplantation for the treatment of clostridium difficile infection: a systematic review.by systematic review, we assessed the impact of fecal microbiota transplantation (fmt) for the treatment of clostridium difficile (cd)-associated diarrhea.201424440934
acidified nitrite: a host defence against colonization with c. difficile spores?proton pump inhibitor (ppi) use increases the risk of clostridium difficile infection (cdi) despite c. difficile spores being acid resistant. swallowed saliva contains nitrite which reacts with gastric acid, producing bactericidal nitrogen oxides. with 5mm nitrite at ph 2 (reflecting normal gastric conditions) all c. difficile spores were killed within 15 min. no reduction in count was seen with the same nitrite concentration at ph 5, representing gastric conditions in patients taking ppis, even ...201424440371
efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent clostridium difficile infection.the prevalence of recurrent clostridium difficile infection (rcdi) is increasing; fecal microbiota transplantation (fmt) is an effective therapy. however, there have been no studies of the efficacy of a single session of combined enteral and colonic fmt or characterizations of changes in the microbiota between donors and recipients. we performed a study of 27 patients with rcdi who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. patients ...201424440222
a novel subtyping assay for detection of clostridium difficile virulence genes.this proof-of-concept study demonstrates the application of a novel nucleic acid detection platform to detect clostridium difficile in subjects presenting with acute diarrheal symptoms. this method amplifies three genes associated with c. difficile infection, including genes and deletions (cdtb and tcdc) associated with hypervirulence attributed to the nap1/027/bi strain. amplification of dna from the tcdb, tcdc, and cdtb genes was performed using a droplet-based sandwich platform with quantitat ...201424434086
fecal microbiota transplantation for refractory clostridium difficile colitis in solid organ transplant recipients.fecal microbiota transplantation (fmt) has been shown to be safe and efficacious in individuals with refractory clostridium difficile. it has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. we describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by c. difficile after fmt. both recipients required two fmts to achieve resolution of their symptoms an ...201424433460
an examination of longitudinal cauti, ssi, and cdi rates from key hhs data systems.in response to the growing concern about healthcare-associated infections (hais), us department of health and human services (hhs) developed the national action plan to prevent healthcare-associated infections. a key focus of the action plan is the setting of hai metrics and targets and the enhancement and development of data systems to support hai surveillance.201424430270
colonization with clostridium difficile in children with cancer.clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus. usually it does not cause disease unless a patient who is colonized with toxin-producing strains has been treated with antibiotics, particularly those that change the anaerobic flora of the large intestine.201324427503
prevention of clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam.sporulation of clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. however, the influence of antibiotics on sporulation is unclear. the objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on c. difficile sporulation in vitro.201424422950
comparison of chromid agar and clostridium difficile selective agar for effective isolation of c. difficile from stool specimens.chromid clostridium difficile agar (idcd; biomérieux sa, france) is a recently developed chromogenic medium for rapid and specific isolation of c. difficile. we compared the performance of idcd with that of clostridium difficile selective agar (cdsa).201424422190
combination of culture, antigen and toxin detection, and cytotoxin neutralization assay for optimal clostridium difficile diagnostic testing.there has been a growing interest in developing an appropriate laboratory diagnostic algorithm for clostridium difficile, mainly as a result of increases in both the number and severity of cases of c difficile infection in the past decade. a c difficile diagnostic algorithm is necessary because diagnostic kits, mostly for the detection of toxins a and b or glutamate dehydrogenase (gdh) antigen, are not sufficient as stand-alone assays for optimal diagnosis of c difficile infection. in addition, ...201324421808
treatment of relapsing clostridium difficile infection using fecal microbiota transplantation.clostridium difficile infection (cdi) has become a global concern over the last decade. in the united states, cdi escalated in incidence from 1996 to 2005 from 31 to 64/100,000. in 2010, there were 500,000 cases of cdi with an estimated mortality up to 20,000 cases a year. the significance of this problem is evident from the hospital costs of over 3 billion dollars annually. fecal microbiota transplant (fmt) was first described in 1958 and since then about 500 cases have been published in litera ...201324421645
a low complexity rapid molecular method for detection of clostridium difficile in stool.here we describe a method for the detection of clostridium difficile from stool using a novel low-complexity and rapid extraction process called heat elution (he). the he method is two-step and takes just 10 minutes, no specialist instruments are required and there is minimal hands-on time. a test method using he was developed in conjunction with loop-mediated isothermal amplification (lamp) combined with the real-time bioluminescent reporter system known as bart targeting the toxin b gene (tcdb ...201424416173
antimicrobial stewardship program implementation in a medical intensive care unit at a tertiary care hospital in saudi arabia.antimicrobial stewardship programs (asps) have shown to prevent the emergence of antimicrobial resistance associated with an inappropriate antimicrobial use. the primary objective of this study was to compare the prescribing appropriateness rate of the empirical antibiotic therapy before and after the asp implementation in a tertiary care hospital. secondary objectives include the rate of clostridium difficile-associated diarrhea (cdad), physicians' acceptance rate, patient's intensive care unit ...201524413857
from stool transplants to next-generation microbiota therapeutics.the epidemic of clostridium difficile infection fueled by new virulent strains of the organism has led to increased use of fecal microbiota transplantation (fmt). the procedure is effective for even the most desperate cases after failure of multiple courses of antibiotics. the approach recognizes microbiota to be integral to normal human physiology, and microbiota being used in fmt represents a new class of therapeutics. imbalance in the composition and altered activity of the microbiota are ass ...201424412527
antibiotic resistance: the challenge from an industry perspective.trained in medical microbiology and infectious diseases in the uk, glenn tillotson has over 20 years pharmaceutical experience in various areas, including clinical research, marketing, scientific communications, strategic development and global launch programs. mainly in the field of anti-infectives, tillotson has been instrumental in the development of ciprofloxacin and moxifloxacin, as well as other drugs in the bayer portfolio. after leaving bayer, he worked as a consultant microbiologist and ...200924410641
clostridium difficile infection: molecular pathogenesis and novel therapeutics.the gram-positive anaerobic bacterium clostridium difficile produces toxins a and b, which can cause a spectrum of diseases from pseudomembranous colitis to c. difficile-associated diarrhea. a limited number of c. difficile strains also produce a binary toxin that exhibits adp ribosyltransferase activity. here, the structure and the mechanism of action of these toxins as well as their role in disease are reviewed. nosocomial c. difficile infection is often contracted in hospital when patients tr ...201424410618
vitamin d status and severity of clostridium difficile infections: a prospective cohort study in hospitalized adults.clostridium difficile is the most common cause of nosocomial diarrhea, affecting up to 10% of hospitalized patients. preliminary studies suggest an association between vitamin d status and c difficile infections (cdis). our goal was to investigate whether serum 25-hydroxyvitamin d (25(oh)d) levels are associated with cdi severity.201524408036
prevention of clostridium difficile infection in rural hospitals.prevention of clostridium difficile infection (cdi) remains challenging across the spectrum of health care. there are limited data on prevention practices for cdi in the rural health care setting.201424406257
patients' experience and perception of hospital-treated clostridium difficile infections: a qualitative study.clostridium difficile is the leading cause of antibiotic-associated diarrhea and an important source of nosocomial infection. clinical manifestations can range from mild diarrhea to lethal pseudomembranous colitis. little is known about the burden of c. difficile infections (cdi) in patients.201424403096
proteomic analysis of a nap1 clostridium difficile clinical isolate resistant to metronidazole.clostridium difficile is an anaerobic, gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. metronidazole is currently the first-line treatment for mild to moderate c. difficile infections. our laboratory isolated a strain of c. difficile with a stable resistance phenotype to metronidazole. a shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates.201424400070
use of fidaxomicin through a nasogastric tube for the treatment of septic shock caused by clostridium difficile infection in a patient with oral cancer admitted to the surgical critical care unit. 201324399354
fecal microbiota transplantation: effectiveness, complexities, and lingering concerns.the mammalian colon is home to a microbial ecosystem that enhances resistance to infection, stimulates mucosal immune defenses, synthesizes essential vitamins, and promotes caloric uptake by hydrolyzing complex carbohydrates. the bacterial populations inhabiting the gut are complex and vary between different individuals. clinical and experimental studies reveal that the colonic microbiota can enhance or ameliorate intestinal and systemic inflammatory diseases. because of its potential to enhance ...201424399149
characterization of clostridium perfringens in the feces of adult horses and foals with acute enterocolitis.up to 60% of cases of equine colitis have no known cause. to improve understanding of the causes of acute colitis in horses, we hypothesized that clostridium perfringens producing enterotoxin (cpe) and/or beta2 toxin (cpb2) are common and important causes of severe colitis in horses and/or that c. perfringens producing an as-yet-undescribed cytotoxin may also cause colitis in horses. fecal samples from 55 horses (43 adults, 12 foals) with clinical evidence of colitis were evaluated by culture fo ...201424396174
evaluation of the diagnostic performance of the xpert clostridium difficile assay and its comparison with the toxin a/b enzyme-linked fluorescent assay and in-house real-time pcr assay used for the detection of toxigenic c. difficile.clostridium difficile genes or toxin can be detected using several laboratory techniques. in this study, we compared the performance of the xpert c. difficile assay with that of a toxin a/b enzyme-linked fluorescent immunoassay (elfa) and an in-house real-time pcr assay for the tcdb gene.201424395702
the roles of toxin a and toxin b in clostridium difficile infection: insights from the gnotobiotic piglet model.we recently published our findings indicating that anti-tcdb antibodies were effective as treatment for c. difficile infection, but that anti-tcda actually worsened prognosis in the gnotobiotic piglet model. to further investigate the roles of the two toxins, we administered purified toxins separately or together, systemically, to piglets and found that both toxins, either alone or together, are able to elicit severe lesions systemically and are also able to cross into the gut lumen and cause la ...201624394234
clostridium difficile: deleterious impact on hematopoietic stem cell transplantation.c. difficile infection (cdi), the most common cause of hospital-acquired diarrhea, is very frequent after hematopoietic stem cell transplantation (hsct). recent publications suggest it affects between 6 % and 20 % of hsct recipients during the first year and is more common following allogeneic transplant (allo-hsct). the best diagnostic strategy remains to be defined, but molecular testing for the toxin genes by polymerase chain reaction (pcr) seems to be replacing the traditional enzyme immunoa ...201424390550
a clinician's primer on the role of the microbiome in human health and disease.the importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome. although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. as such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human mic ...201424388028
new routes towards reutericyclin analogues.a range of n-acylpyrrolo[3,4-c]isoxazoles and derived n-acyltetramides has been prepared via a nitrile oxide dipolar cycloaddition approach, as analogues of the acyltetramic acid metabolite reutericyclin, of interest for its antibiotic potential against gram-positive bacteria including hospital-acquired infections of resistant clostridium difficile.201424382380
low vitamin d level is an independent predictor of poor outcomes in clostridium difficile-associated diarrhea.the incidence, recurrence, and all-cause mortality rate for clostridium difficile-associated diarrhea (cdad) has increased markedly over the past 10 years despite treatment. low vitamin d levels are known to impair immune responses to infection and are associated with increased mortality. we compared the role of patient comorbidity measured by the charlson comorbidity index (cci) with vitamin d levels to ascertain whether vitamin d levels were an independent variable affecting the outcome of cda ...201424381644
clostridium difficile-associated disease: adherence with current guidelines at a tertiary medical center.to assess adherence with the the society for healthcare epidemiology of america (shea)/ the infectious diseases society of america (idsa) guidelines for management of clostridium difficile (c. difficile)-associated disease (cdad) at a tertiary medical center.201324379582
parameters for the mathematical modelling of clostridium difficile acquisition and transmission: a systematic review.mathematical modelling of clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. the objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of clostridium difficile transmission.201324376797
comparison of oral vancomycin capsule and solution for treatment of initial episode of severe clostridium difficile infection.vancomycin is recommended as a first-line therapy for severe clostridium difficile infection (cdi). due to the high cost of commercially available vancomycin capsules, hospitals frequently compound oral solution despite a lack of data comparing outcomes. this study was conducted to determine treatment outcome differences based on oral vancomycin formulation.201524375999
single nucleotide polymorphisms of the tcdc gene and presence of the binary toxin gene predict recurrent episodes of clostridium difficile infection.to identify clostridium difficile genotypes, which are associated with recurrent c difficile infection (rcdi).201424374512
epidemiology of clostridium difficile infection among active duty united states military personnel (1998-2010).clostridium difficile associated disease (cdad) has risen in incidence and the experience in the us military has not been described.201324373384
faecal microbiota transplantation for clostridium difficile infection.to review the current clinical literature regarding the use of fecal microbiota transplantation (fmt) for severe and recurrent clostridium difficile disease (cdad).201424372725
small animal models for the study of clostridium difficile disease pathogenesis.clostridium difficile is the leading cause of bacterial antibiotic-associated diarrhoea in hospitals in the developed world. despite this notoriety, the complex mechanisms employed by this pathogen to overcome innate host defences and induce fulminant disease are poorly understood. various animal models have been used extensively for c. difficile research to study disease pathogenesis. until recently, the most commonly used c. difficile disease model has utilised hamsters; however, mouse and pig ...201424372713
predictors of first recurrence in clostridium difficile-associated disease. a study of 306 patients hospitalized in a romanian tertiary referral center.clostridium difficile is recognized as the major cause of nosocomial gastroenteritis usually related to antibiotic treatment. although treatable, c. difficile--associated disease (cdad) tends to recur in many patients. the purpose of the study was to analyze the risk factors for recurrence in patients with cdad after the first treatment with vancomycin, metronidazole or both.201324369321
fecal microbiota transplantation: a practical update for the infectious disease specialist.fecal microbiota transplantation (fmt) has been shown to be a superior therapeutic modality for the treatment of recurrent clostridium difficile infection (rcdi). recently the us food and drug administration (fda) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. consequently, the fda determined that prescribers of fmt must possess an approved investigational new drug (ind) permit to administer fmt for the purpose of ...201424368622
antibiotic prophylaxis for hip fracture surgery: three-dose cefuroxime versus single-dose gentamicin and amoxicillin.to compare a 3-dose cefuroxime regimen with a single-dose gentamicin and amoxicillin regimen as antibiotic prophylaxis for hip hemiarthroplasty in terms of microbiological outcome.201324366793
cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.to examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis.201424365863
rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (he) and he-related hospitalizations in a 6-month, randomized, controlled trial (rct). we performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use.201424365449
mitogen-activated protein kinase/iκb kinase/nf-κb-dependent and ap-1-independent cx3cl1 expression in intestinal epithelial cells stimulated with clostridium difficile toxin a.clostridium difficile toxin a causes acute colitis associated with inflammatory cell infiltration and increased production of proinflammatory mediators. although cx3cl1 (fractalkine) plays a role in chemoattracting monocytes/macrophages, nk cells, and t cells, little information is available on the regulated expression of cx3cl1 in response to toxin a stimulation. in this study, we investigated the role of c. difficile toxin a on cx3cl1 induction in intestinal epithelial cells. stimulation of mu ...201424362517
structure of clostridium difficile pilj exhibits unprecedented divergence from known type iv pilins.type iv pili are produced by many pathogenic gram-negative bacteria and are important for processes as diverse as twitching motility, cellular adhesion, and colonization. recently, there has been an increased appreciation of the ability of gram-positive species, including clostridium difficile, to produce type iv pili. here we report the first three-dimensional structure of a gram-positive type iv pilin, pilj, demonstrate its incorporation into type iv pili, and offer insights into how the type ...201324362261
[outbreak of clostridium difficile infection in a hematopoietic stem cell transplantation unit]. 201424361148
diarylacylhydrazones: clostridium-selective antibacterials with activity against stationary-phase cells.current antibiotics for treating clostridium difficile infections (cdi), that is, metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. the shortcomings of these agents are attributed to their low selectivity for c. difficile over normal gut microflora and their ineffectiveness against c. difficile spores. this letter reports that certain diarylacylhydrazones identified during a high-throug ...201424360560
characterization of the sigd regulon of c. difficile and its positive control of toxin production through the regulation of tcdr.clostridium difficile intestinal disease is mediated largely by the actions of toxins a (tcda) and b (tcdb), whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. in b. subtilis, the sigma factor sigd controls flagellar synthesis, motility, and vegetative autolysins. a homolog of sigd encoding gene is present in the c.difficile 630 genome. we constructed a sigd mutant in c. difficile 630 ∆erm to analyze the regulon of sigd using a glob ...201324358307
treatment strategies for recurrent clostridium difficile infection.recurrent clostridium difficile infection represents a major clinical challenge. treatment is often based on empiric selection from relatively few options supported by limited clinical evidence.201324357868
the relationship of bedside nurses' emotional intelligence with quality of care.emotional intelligence, a predictor of productivity and success, may impact behaviors responsible for quality of care. this study examined if emotional intelligence of units' bedside nurses is related to the quality of care delivered to the patients. in this study, emotional intelligence was found to be correlated to the number of clostridium difficile infections, mrsa infections, patient falls with injury, and pressure ulcer screenings (p < .001) in the inpatient acute care setting.201524356579
faecal microbiota transplantation and bacteriotherapy for recurrent clostridium difficile infection: a retrospective evaluation of 31 patients.recurrent clostridium difficile infection (cdi) is a significant problem due to its increased incidence and severity. failure rates for standard antibiotic therapies are high. in our hospital, faecal microbiota transplantation (fmt), or instillation of a culture mixture of known enteric bacteria in saline as rectal bacteriotherapy (rbt), has long been used as 'rescue therapy' in patients with recurrent disease, in whom repeated courses of standard antibiotic treatment have failed. we wanted to e ...201424354958
comparison of illumigene, simplexa, and amplivue clostridium difficile molecular assays for diagnosis of c. difficile infection.we compared the performance of the simplexa universal direct (focus diagnostics) and amplivue (quidel corporation) assays to that of the illumigene assay (meridian bioscience, inc.) for the diagnosis of clostridium difficile infection. two hundred deidentified remnant diarrheal stool specimens were tested by the simplexa, amplivue, and illumigene methods. specimens with discrepant results among the three assays and a representative number of concordant specimens were further evaluated by toxigen ...201424352999
the incidence and clinical symptomatology of clostridium difficile infections in a community setting in a cohort of danish patients attending general practice.clostridium difficile infection (cdi) is gradually being recognised as a cause of morbidity in the community. we investigated the incidence and clinical characteristics of cdi in a community setting and characterised the c. difficile strains by toxin gene profiling and polymerase chain reaction (pcr) ribotyping. patients included in the study had attended general practice, primarily because of diarrhoea; cdi patients (259 patients; 121 <2 years of age) had positive cultures for toxigenic c. diff ...201424352841
probiotics for the prevention of antibiotic-associated diarrhea and clostridium difficile infection among hospitalized patients: systematic review and meta-analysis.antibiotic-associated diarrhea (aad) and clostridium difficile infection (cdi) are associated with high morbidity, mortality, and health care costs. probiotics may mitigate the existing disease burden. we performed a systematic review and meta-analysis to evaluate the efficacy of co-administration of probiotics with antibiotics in preventing these adverse outcomes in adult inpatients.201324348885
ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota.the intestinal microbiota is a microbial ecosystem of crucial importance to human health. understanding how the microbiota confers resistance against enteric pathogens and how antibiotics disrupt that resistance is key to the prevention and cure of intestinal infections. we present a novel method to infer microbial community ecology directly from time-resolved metagenomics. this method extends generalized lotka-volterra dynamics to account for external perturbations. data from recent experiments ...201324348232
molecular epidemiology of clostridium difficile in a tertiary hospital of china.clostridium difficile infection (cdi) is caused by toxin-producing strains. it accounts for 20-30 % of antibiotic-associated diarrhoea and particularly accounts for 90 % of pseudomembranous colitis. the epidemiological study of c. difficile is thus important. in this study, we report the molecular epidemiology and ward distribution of c. difficile in a tertiary hospital of china. a total of 161 toxigenic strains were isolated from 1845 patients originating from different wards and the strains we ...201424344206
treating clostridium difficile infection. 201424344151
predictors of clostridium difficile infections in hospitalized children.recent studies report an increasing incidence of clostridium difficile infections (cdis) in children and suggest that cdis may occur outside known populations at risk.201424343932
[survival advantage for colectomy in fulminant clostridium difficile colitis: results of a systematic review of the literature]. 201424342951
recombinant antigens based on toxins a and b of clostridium difficile that evoke a potent toxin-neutralising immune response.infection with the bacterium clostridium difficile causes symptoms ranging from mild to severe diarrhoea with life-threatening complications and remains a significant burden to healthcare systems throughout the developed world. two potent cytotoxins, tcda and tcdb are the prime mediators of the syndrome and rapid neutralisation of these would afford significant benefits in disease management. in the present study, a broad range of non-toxic, recombinant fragments derived from tcda and tcdb were ...201424342251
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