Publications

microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in clostridium difficile infection.	faecal microbiome transplantation (fmt) has generated huge recent interest as it presents a potential solution to a significant clinical problem--the increasing incidence of clostridium difficile infection (cdi). in the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. in the longer term, enhanced understanding of the mechanisms of action of fmt may potentiate novel therapie ...	2015	25193538
smt19969 as a treatment for clostridium difficile infection: an assessment of antimicrobial activity using conventional susceptibility testing and an in vitro gut model.	we investigated the efficacy of the novel antimicrobial agent smt19969 in treating simulated clostridium difficile infection using an in vitro human gut model.	2015	25190720
fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.	fecal microbiota transplantation (fmt) is a safe and effective therapy for adults with recurrent clostridium difficile colitis, but data regarding fmt in children are limited and focus on colonoscopic administration of fmt. we present 10 consecutive children who received fmt via nasogastric tube for treatment of recurrent c difficile infection. median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. median follow-up was 44 days, and 90% of patients resolved their c diffi ...	2015	25162365
epidemiology of clostridium difficile: a hospital-based descriptive study in argentina and mexico.	a prospective study was conducted in four tertiary hospitals in argentina and mexico in order to describe the occurrence of clostridium difficile infection (cdi) in these settings. the objective was to evaluate the incidence of cdi in at-risk populations in argentina (one center) and mexico (three centers) and to further explore potential study sites for vaccine development in this region. a prospective, descriptive, cdi surveillance study was conducted among hospitalized patients aged ≥40 years ...	2015	25179510
isolation and characterization of a new clostridium difficile ribotype during a prospective study in a hospital in italy.		2015	25240292
antimicrobial susceptibility patterns of clostridium difficile strains belonging to different polymerase chain reaction ribotypes isolated in poland in 2012.	in the beginning of 2012, a study was conducted to obtain an overview of clostridium difficile infections (cdis) in polish hospitals. the collection of 83 toxigenic c. difficile isolates obtained from this hospital-based survey was used to identify antimicrobial susceptibility patterns. among the c. difficile isolates analyzed, 48 (57.8%) belonged to pcr ribotype 027, 21 (25.3%) to its closely related pcr ribotype 176, and 14 (16.9%) to different pcr ribotypes. seventy one (85.5%) isolates were ...	2015	25242196
the roles of host and pathogen factors and the innate immune response in the pathogenesis of clostridium difficile infection.	clostridium difficile (c. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. the clinical manifestation of c. difficile infection (cdi) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. c. difficile ...	2015	25242213
β-lactam/β-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis of randomized controlled trials.	data on the relative efficacy of β-lactam/β-lactamase inhibitors (bl/blis) versus carbapenems are scant.	2015	25261419
fecal microbiota transplantation for treatment of clostridium difficile infection.		2015	25036411
cyclophilin-facilitated membrane translocation as pharmacological target to prevent intoxication of mammalian cells by binary clostridial actin adp-ribosylated toxins.	clostridium botulinum c2 toxin, clostridium perfringens iota toxin and clostridium difficile cdt belong to the family of binary actin adp-ribosylating toxins and are composed of a binding/translocation component and a separate enzyme component. the enzyme components adp-ribosylate g-actin in the cytosol of target cells resulting in depolymerization of f-actin, cell rounding and cell death. the binding/translocation components bind to their cell receptors and form complexes with the respective en ...	2015	25058685
ambulatory-treated clostridium difficile infection: a comparison of community-acquired vs. nosocomial infection.	the purpose of this study was to identify the clinical outcomes of ambulatory-treated clostridium difficile infection (cdi) and risk factors associated with community-associated cdi (ca-cdi). adult patients diagnosed with cdi in the institutional or ambulatory-care setting between 1 april 2005 and 30 april 2011, with no other cdi diagnosis in the previous 180 days, and who purchased an ambulatory, anti-cdi agent within 7 days of cdi diagnosis were included. a total of 1201 patients were included ...	2015	25058469
intestinal microbiota transplantation, a simple and effective treatment for severe and refractory clostridium difficile infection.	restoring normal fecal flora through intestinal microbiota transplantation (imt) was successful in curing recurrent clostridium difficile infection (cdi). however, only a few cases have been reported of imt being utilized for the treatment of severe or fulminant cdi.	2015	25052150
recent evolution of antibiotic resistance in the anaerobes as compared to previous decades.	evolution of antibiotic resistance in the anaerobes was reviewed using recent data covering 2000-2013 as compared to previous years. all studies reported growing moxifloxacin resistance in bacteroides/parabacteroides spp. in europe and usa and in clostridium difficile in europe. in half or more studies, the resistance rates in bacteroides/parabacteroides spp. to amoxicillin-clavulanate or ampicillin-sulbactam and clindamycin rose. in some studies, an increase in resistance was found in bacteroid ...	2015	24875330
clinical impact of clostridium difficile colonization.	clostridium difﬁcile can cause antibiotic-associated diarrhea in hospitalized patients. asymptomatic colonization by c. difficile is common during the neonatal period and early infancy, ranging from 21% to 48%, and in childhood. the colonization rate of c. difficile in adult hospitalized patients shows geographic variation, ranging from 4.4% to 23.2%. asymptomatic carriage in neonates caused no further disease in many studies, whereas adult patients colonized with toxigenic c. difficile were pro ...	2015	24890755
transplant related outcomes in patients with hematopoietic stem cell transplant with clostridium difficile associated diarrhea.		2015	24766526
clostridium difficile binary toxin cdt: mechanism, epidemiology, and potential clinical importance.	binary toxin (cdt) is frequently observed in clostridium difficile strains associated with increased severity of c. difficile infection (cdi). cdt belongs to the family of binary adp-ribosylating toxins consisting of two separate toxin components: cdta, the enzymatic adp-ribosyltransferase which modifies actin, and cdtb which binds to host cells and translocates cdta into the cytosol. cdtb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. adp-ribosylation i ...	2015	24253566
validation of a clinical prediction scale for hospital-onset clostridium difficile infection.	the aim of this study was to validate a clinical prediction scale for hospital-onset clostridium difficile infection (cdi).	2015	24172178
risk factors for clostridium difficile-associated diarrhea among hospitalized adults with fecal toxigenic c. difficile colonization.	patients with toxigenic clostridium difficile colonization (tcdc) are at risk of developing c. difficile-associated diarrhea (cdad). however, the risk factors of hospitalized patients with tcdc developing cdad are not clear.	2015	24064285
biofilm formation by clostridium difficile.	clostridium difficile infection (cdi) is a major healthcare-associated disease worldwide. recurring infections and increasing antibiotic resistance have complicated treatment of cdi. while c. difficile spores are important for transmission and persistence of cdi, other factors such as gut colonization and formation of bacterial communities in the gut may also contribute to pathogenesis and persistence, but have not been well investigated. recently, we reported that important clinical c. difficil ...	2015	23892245
horizontal gene transfer in human pathogens.	horizontal gene transfer has a tremendous impact on the genome plasticity, adaptation and evolution of bacteria. horizontally transferred mobile genetic elements are involved in the dissemination of antibiotic resistance and virulence genes, thus contributing to the emergence of novel "superbugs". this review provides update on various mechanisms of horizontal gene transfer and examines how horizontal gene transfer contributes to the evolution of pathogenic bacteria. special focus is paid to the ...	2015	23862575
[multiresistant organisms].	infections caused by multidrug resistant (mdr) organisms are becoming more frequently in daily practice and are associated with an increase in duration of treatment and mortality. during the past decades, particular attention in the field of mdr pathogens was paid to methicillin-resistant staphylococcus aureus (mrsa). for the last years, mdr gram-negative organisms, with e.g., "extended-spectrum beta-lactamases" (esbl), have been gaining a growing significance. currently, treatment of infections ...	2015	23824619
new drugs and strategies for management of clostridium difficile colitis.	approaches for management of clostridium difficile infection continually evolve as research reveals shifts in epidemiology, microbial pathogenesis, disease severity states, and response to therapy. these new discoveries significantly impact diagnostic and therapeutic strategies, given the high morbidity associated with this common nosocomial infectious diarrhea. critically ill patients are at an increased risk of developing diarrheal illness like c. difficile and succumbing to potentially fatal ...	2015	23753229
[anaerobic bacteria 150 years after their discovery by pasteur].	in 2011 we celebrated the 150th anniversary of the discovery of anaerobic bacteria by louis pasteur. the interest of the biomedical community on such bacteria is still maintained, and is particularly focused on clostridium difficile. in the past few years important advances in taxonomy have been made due to the genetic, technological and computing developments. thus, a significant number of new species related to human infections have been characterised, and some already known have been reclassi ...	2015	23648369
molecular typing and epidemiology of clostridium difficile in respiratory care wards of central taiwan.	in industrialized countries, clostridium difficile is the major cause of nosocomial diarrhea. this study involved a broad overview of baseline epidemiology for c. difficile in taiwan.	2015	23726464
cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of clostridium difficile infection in the united states.	fidaxomicin is a novel treatment for clostridium difficile infections (cdis). this new treatment, however, is associated with a higher acquisition cost compared with alternatives. the objective of this study was to evaluate the cost-effectiveness of fidaxomicin or oral vancomycin for the treatment of cdis.	2015	23538181
[dificid: fewer recurrences of clostridium difficile].		2015	23379054
donor recruitment for fecal microbiota transplantation.	increasing demand for fecal microbiota transplantation (fmt) has created a need for stool banks sourced from long-term healthy donors. here, we describe our experience in recruiting and screening fecal donors.	2015	26070003
profiling humoral immune responses to clostridium difficile-specific antigens by protein microarray analysis.	clostridium difficile is an anaerobic, gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. several studies have reported associations between humoral immunity and the clinical course of c. difficile infection (cdi). host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (elisa) techniques. herein, we report the first use of a novel protein microarray assay to d ...	2015	26178385
production of biologically active scfv and vhh antibody fragments in bifidobacterium longum.	bifidobacteria constitute a significant part of healthy intestinal microbiota in adults and infants and present a promising platform for construction of genetically modified probiotic agents for treatment of gastrointestinal disorders. in this study, three strains of bifidobacterium longum were constructed that express and secrete biologically active single-chain antibodies against human tnf-α and clostridium difficile exotoxin a. anti-tnf-α scfv antibody d2e7 was produced at the level of 25 μg ...	2015	25994292
probiotics for the primary and secondary prevention of c. difficile infections: a meta-analysis and systematic review.	clostridium difficile infections are a global clinical concern and are one of the leading causes of nosocomial outbreaks. preventing these infections has benefited from multidisciplinary infection control strategies and new antibiotics, but the problem persists. probiotics are effective in preventing antibiotic-associated diarrhea and may also be a beneficial strategy for c. difficile infections, but randomized controlled trials are scarce. this meta-analysis pools 21 randomized, controlled tria ...	2015	27025619
prebiotic preferences of human lactobacilli strains in co-culture with bifidobacteria and antimicrobial activity against clostridium difficile.	to evaluate robustness, prebiotic utilization of lactobacillus paracasei f8 and lactobacillus plantarum f44 in mono- and co-cultures with bifidobacterium breve 46 and bifidobacterium animalis sub sp. lactis 8 : 8 and antimicrobial activity of co-culture against clostridium difficile.	2015	26381324
the intestinal microbiota composition and weight development in children: the koala birth cohort study.	to investigate whether the intestinal microbiota composition in early infancy is associated with subsequent weight development in children.	2015	25298274
regulation of clostridium difficile spore formation by the spoiiq and spoiiia proteins.	sporulation is an ancient developmental process that involves the formation of a highly resistant endospore within a larger mother cell. in the model organism bacillus subtilis, sporulation-specific sigma factors activate compartment-specific transcriptional programs that drive spore morphogenesis. σg activity in the forespore depends on the formation of a secretion complex, known as the "feeding tube," that bridges the mother cell and forespore and maintains forespore integrity. even though the ...	2015	26465937
spore cortex hydrolysis precedes dipicolinic acid release during clostridium difficile spore germination.	bacterial spore germination is a process whereby a dormant spore returns to active, vegetative growth, and this process has largely been studied in the model organism bacillus subtilis. in b. subtilis, the initiation of germinant receptor-mediated spore germination is divided into two genetically separable stages. stage i is characterized by the release of dipicolinic acid (dpa) from the spore core. stage ii is characterized by cortex degradation, and stage ii is activated by the dpa released du ...	2015	25917906
morphological and genetic characterization of group i clostridium botulinum type b strain 111 and the transcriptional regulator spoiiid gene knockout mutant in sporulation.	clostridium botulinum is a heat-resistant spore-forming bacterium that causes the serious paralytic illness botulism. heat-resistant spores may cause food sanitation hazards and sporulation plays a central role in the survival of c. botulinum. we observed morphological changes and investigated the role of the transcriptional regulator spoiiid in the sporulation of c. botulinum type b strain 111 in order to elucidate the molecular mechanism in c. botulinum. c. botulinum type b formed heat-resista ...	2015	25652599
diverse mechanisms regulate sporulation sigma factor activity in the firmicutes.	sporulation allows bacteria to survive adverse conditions and is essential to the lifecycle of some obligate anaerobes. in bacillus subtilis, the sporulation-specific sigma factors, σ(f), σ(e), σ(g), and σ(k), activate compartment-specific transcriptional programs that drive sporulation through its morphological stages. the regulation of these sigma factors was predicted to be conserved across the firmicutes, since the regulatory proteins controlling their activation are largely conserved. howev ...	2015	25646759
spoiiid-mediated regulation of σk function during clostridium difficile sporulation.	the spore-forming bacterial pathogen clostridium difficile is a leading cause of health-care-associated diarrhea worldwide. although c. difficile spore formation is essential for disease transmission, the regulatory pathways that control this developmental process have only been partially characterized. in the well-studied spore-former bacillus subtilis, the highly conserved σ(e) , spoiiid and σ(k) regulatory proteins control gene expression in the mother cell to ensure proper spore formation. t ...	2015	25393584
prevalence of gastrointestinal pathogenic bacteria in patients with diarrhoea attending groote schuur hospital, cape town, south africa.	diarrhoea due to gastrointestinal infections is a significant problem facing the south african (sa) healthcare system. infections can be acquired both from the community and from the hospital environment itself, the latter acting as a reservoir for potential pathogenic bacteria.	2015	26242530
conventional and molecular methods in the diagnosis of community-acquired diarrhoea in children under 5 years of age from the north-eastern region of poland.	the purpose of this study was to determine the main causative agents of community-acquired acute diarrhoea in children using conventional methods and pcr.	2015	26159845
predictors of monomicrobial necrotizing soft tissue infections.	broad-spectrum antibiotic therapy is critical in the management of necrotizing soft tissue infections (nsti) in the emergency setting. clindamycin often is included empirically to cover monomicrobial gram-positive pathogens but probably is of little value for polymicrobial infections and is associated with significant side effects, including the induction of clostridium difficile colitis. however, there have been no studies predicting monomicrobial infections prior to obtaining cultures. the pur ...	2015	26110633
probiotics for the prevention of antibiotic-associated diarrhoea in older patients: a systematic review.	here, we evaluated the efficacy of probiotic interventions in prevention of antibiotic-associated diarrhoea (aad) and clostridium difficile diarrhoea (cdd) in older patients.	2015	25805164
glucosyltransferase activity of clostridium difficile toxin b is essential for disease pathogenesis.	clostridium difficile tcdb harbors a glucosyltransferase that targets host rho gtpases. however, the role of the enzyme activity in the induction of host intestinal disease has not been demonstrated. in this study, we established a mouse acute intestinal disease model by cecum injection of wild type and glucosyltransferase-deficient tcdb and a chronic model by delivering toxin intraluminally via engineered surrogate host bacillus megaterium. we demonstrated, for the first time, that the glucosyl ...	2015	26091306
a chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin b and the receptor binding domain of toxin a induces protective immunity against clostridium difficile infection in mice and hamsters.	clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. the pathogenicity of c. difficile is mainly mediated by the release of 2 large potent exotoxins, toxin a (tcda) and toxin b (tcdb), both of which require neutralization to prevent disease occurrence. we have generated a novel chimeric protein, designated mtcd138, comprised of the glucosyltransferase and cysteine proteinase domains of tcdb and the receptor binding domain of tcda a ...	2015	26036797
mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies.	novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (vhhs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against shiga, botulinum, clostridium difficile, anthrax, and ricin toxins. however, the mechanisms by which these so-called bispecific vhh heterodimers promote toxin neutralization remain poorly understood. in the current study we produced a new collection of ricin-specific vhh heterodimers, as well as ...	2015	26396190
structural basis of proline-proline peptide bond specificity of the metalloprotease zmp1 implicated in motility of clostridium difficile.	clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. in common with other pathogenic bacteria, c. difficile secretes proteins involved in adhesion, colonization, and dissemination. the recently identified zmp1 is an extracellular metalloprotease showing a unique specificity for pro-pro peptide bonds. the endogenous substrates of zmp1 are two surface proteins implicated in adhesion of c. difficile to surface proteins of human cel ...	2015	26211609
unlocking the sporicidal potential of ethanol: induced sporicidal activity of ethanol against clostridium difficile and bacillus spores under altered physical and chemical conditions.	due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. however, alcohols lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats.	2015	26177038
diverse supramolecular structures formed by self-assembling proteins of the bacillus subtilis spore coat.	bacterial spores (endospores), such as those of the pathogens clostridium difficile and bacillus anthracis, are uniquely stable cell forms, highly resistant to harsh environmental insults. bacillus subtilis is the best studied spore-former and we have used it to address the question of how the spore coat is assembled from multiple components to form a robust, protective superstructure. b. subtilis coat proteins (coty, cote, cotv and cotw) expressed in escherichia coli can arrange intracellularly ...	2015	25872412
protein composition of the outermost exosporium-like layer of clostridium difficile 630 spores.	clostridium difficile spores are considered the morphotype of infection, transmission and persistence of c. difficile infections. there is a lack of information on the composition of the outermost exosporium layer of c. difficile spores. using recently developed exosporium removal methods combined with ms/ms, we have established a gel-free approach to analyze the proteome of the exosporium of c. difficile spores of strain 630. a total of 184 proteins were found in the exosporium layer of c. diff ...	2015	25849250
bacillus amyloliquefaciens as prophylactic treatment for clostridium difficile-associated disease in a mouse model.	probiotics might offer an attractive alternative for standard antibiotic therapy to treat clostridium difficile infections (cdi). we specifically selected a bacillus amyloliquefaciens strain for its high in vitro antibacterial activity against c. difficile and tested its efficacy to prevent cdi in a mouse model.	2015	25800047
safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an esbl-endemic setting.	to evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (asp) in a setting where esbl-producing enterobacteriaceae are endemic.	2015	25473028
prevalence of clostridium difficile among paediatric patients in a tertiary care hospital, coastal karnataka, south india.	the study was intended to analyse the burden of clostridium difficile (c. difficile) and associated intestinal pathogens from children with diarrhoea who were hospitalized in a tertiary care teaching hospital of south india.	2015	25859452
the analysis of the occurrence of nosocomial infections in the neurosurgical ward in the district hospital from 2003-2012.	the patients in the neurosurgical ward are exposed to many risk factors causing nosocomial infections. these factors are related to operations, invasive diagnosing and monitoring of the nervous system and mechanical support of vital functions. therefore, the objective of the undertaken studies was to assess the prevalence and structure of the healthcare-associated infections (hai) in patients hospitalized in the neurosurgical ward in the st. lukas district hospital in tarnów.	2015	26519848
antibacterial discovery and development: from gene to product and back.	concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. infections caused by enterococcus faecium, staphylococcus aureus, klebsiella species, clostridium difficile, acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, and other enterobacteriaceae species represent a major public health b ...	2015	26339625
pathogen transfer and high variability in pathogen removal by detergent wipes.	the rise in health care-associated infections has placed a greater emphasis on cleaning and disinfection practices. the majority of policies advocate using detergent-based products for routine cleaning, with detergent wipes increasingly being used; however, there is no information about their ability to remove and subsequently transfer pathogens in practice.	2015	25997876
kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent.	bacterial resistance to antibiotics continues to grow and pose serious challenges, while the discovery rate for new antibiotics declines. kibdelomycin is a recently discovered natural-product antibiotic that inhibits bacterial growth by inhibiting the bacterial dna replication enzymes dna gyrase and topoisomerase iv. it was reported to be a broad-spectrum aerobic gram-positive agent with selective inhibition of the anaerobic bacterium clostridium difficile. we have extended the profiling of kibd ...	2015	25845866
bloodstream infections among carriers of carbapenem-resistant klebsiella pneumoniae: etiology, incidence and predictors.	carriers of carbapenem-resistant klebsiella pneumoniae (crkp) are increasingly recognised through active surveillance in much of the world. we studied incidence, aetiology and predictors of bloodstream infections (bsi) among such carriers. via a retrospective cohort study conducted in a tertiary care teaching hospital, we examined occurrence of bsi within 45 days of crkp carrier detection. three nested case-control studies were conducted to analyse parameters associated with all-cause (all), gra ...	2015	25636924
evaluation of hydrogen peroxide vapor for the inactivation of nosocomial pathogens on porous and nonporous surfaces.	clostridium difficile spores and multidrug-resistant (mdr) organisms, such as methicillin-resistant staphylococcus aureus (mrsa), vancomycin-resistant enterococcus (vre), and mdr acinetobacter baumannii, are important nosocomial pathogens that are difficult to eliminate from the hospital environment. we evaluated the efficacy of hydrogen peroxide vapor (hpv), a no-touch automated room decontamination system, for the inactivation of a range of pathogens dried onto hard nonporous and porous surfac ...	2015	25564129
disruption of the gut microbiome: clostridium difficile infection and the threat of antibiotic resistance.	clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. central to predisposition to c. difficile infection is disruption of the gut microbiome by antibiotics. being a gram-positive anaerobe, c. difficile is intrinsically resistant to a number of antibiotics. mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. while resistance to ...	2015	26703737
development of gut inflammation in mice colonized with mucosa-associated bacteria from patients with ulcerative colitis.	disturbances in the intestinal microbial community (i.e. dysbiosis) or presence of the microbes with deleterious effects on colonic mucosa has been linked to the pathogenesis of inflammatory bowel diseases. however the role of microbiota in induction and progression of ulcerative colitis (uc) has not yet been fully elucidated.	2015	26697117
colonization resistance of the gut microbiota against clostridium difficile.	antibiotics strongly disrupt the human gut microbiota, which in consequence loses its colonization resistance capacity, allowing infection by opportunistic pathogens such as clostridium difficile. this bacterium is the main cause of antibiotic-associated diarrhea and a current problem in developed countries, since its incidence and severity have increased during the last years. furthermore, the emergence of antibiotic resistance strains has reduced the efficiency of the standard treatment with a ...	2015	27025628
loss of microbiota-mediated colonization resistance to clostridium difficile infection with oral vancomycin compared with metronidazole.	antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as clostridium difficile. metronidazole or oral vancomycin can cure c. difficile infection, and administration of these agents to prevent c. difficile infection in high-risk patients, although not sanctioned by infectious disease society of america guidelines, has been considered. the relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance ar ...	2015	25920320
interactions between the gastrointestinal microbiome and clostridium difficile.	antibiotics have significant and long-lasting effects on the intestinal microbiota and consequently reduce colonization resistance against pathogens, including clostridium difficile. by altering the community structure of the gut microbiome, antibiotics alter the intestinal metabolome, which includes both host- and microbe-derived metabolites. the mechanisms by which antibiotics reduce colonization resistance against c. difficile are unknown yet important for development of preventative and ther ...	2015	26488281
the potential role of nemonoxacin for treatment of common infections.	nemonoxacin , a novel non-ﬂuorinated quinolone, exhibits potent activity against gram-positive bacteria, including mrsa and fluoroquinolone-resistant mrsa, gram-negative and atypical pathogens. this agent also has a reduced propensity for resistance development in many kinds of pathogens.	2015	25529577
mortality, hospital costs, payments, and readmissions associated with clostridium difficile infection among medicare beneficiaries.	the management of clostridium difficile infection (cdi) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. to assess the impact of cdi on mortality, hospital costs, healthcare use, and medicare payments for beneficiaries who were discharged with cdi listed as a secondary international classification of diseases, ninth revision, clinical modification claim diagnosis.	2015	27885315
identification of a novel mutation at the primary dimer interface of gyra conferring fluoroquinolone resistance in clostridium difficile.	the aim of this study was to determine whether alternative resistance mechanisms, other than mutation in the quinolone resistance-determining region (qrdr) of dna gyrase, could confer fluoroquinolone resistance in clostridium difficile. an in vitro-generated c. difficile mutant exhibiting increased fluoroquinolone resistance was isolated through antibiotic selection on ciprofloxacin. the qrdr of this mutant was investigated by chain-termination sequencing and was found to be devoid of mutation. ...	2015	27842877
risk factors for recurrent clostridium difficile infections and strategies to decrease readmissions in a community hospital.	currently there are no universally accepted approaches for the prevention of recurrent clostridium difficile infections (cdi) following the initial infection. several studies have identified common risk factors for the emergence of recurrent cdi. identifying patients at high risk for recurrent cdi through the assessment of risk factors at initial diagnosis could enable health care providers to optimize available treatment options. a vancomycin hydrochloride-tapered regimen may be an effective tr ...	2015	27621508
evaluating the effectiveness of an antimicrobial stewardship intervention on reducing the incidence rate of healthcare-associated clostridium difficile infection.		2015	27437421
[recent epidemiology of clostridium difficile infection in japan].	clostridium difficile (c. difficile) is a major pathogen for diarrhea in hospitalized patients and because of outbreak of highly virulent strain in eu and us, increased length of hospital stay and increased numbers of severe patients and deaths have become major challenges. in recent years, transmissions through community-acquired or food-borne infections are reported. national surveillance has been already performed overseas. guidelines for preventing c. difficile infection (cdi) is available, ...	2015	27004398
[clostridium difficile are on the rise].		2015	26953476
the discovery of a novel antibiotic for the treatment of clostridium difficile infections: a story of an effective academic-industrial partnership.	academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. there is no one model that guarantees success. we describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of curren ...	2015	26949507
fever and cardiac arrest in a patient with a left ventricular assist device.	a 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (lvad) implantation for destination therapy two years ago. he was living an active lifestyle, tracking deer and fishing in a midwestern forest in november. his wife removed an engorged tick on his thorax. a few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. the lvad site had no signs of trauma, drainage, warmth, or tend ...	2015	26380334
multicenter evaluation of the biofire filmarray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis.	the appropriate treatment and control of infectious gastroenteritis depend on the ability to rapidly detect the wide range of etiologic agents associated with the disease. clinical laboratories currently utilize an array of different methodologies to test for bacterial, parasitic, and viral causes of gastroenteritis, a strategy that suffers from poor sensitivity, potentially long turnaround times, and complicated ordering practices and workflows. additionally, there are limited or no testing met ...	2015	25588652
ecological effect of ceftaroline-avibactam on the normal human intestinal microbiota.	ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. the purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. fecal samples were collected on day -1 (within 24 h of ...	2015	25987638
impact of prophylactic levofloxacin on rates of bloodstream infection and fever in neutropenic patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation.	few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (hsct). at our center, levofloxacin prophylaxis was initiated in june 2006 in patients with myeloma who were undergoing autologous hsct. we compared the incidence of bloodstream infection (bsi) and fever and neutropenia (fn) within 30 days of transplantation before (january 2003 to may 2006) and after (june 2006 to apr ...	2015	26150022
binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress.	this study aims to investigate if histo-blood group antigen (hbga) expressing bacteria have any protective role on human norovirus (nov) from acute heat stress. eleven bacterial strains were included, belonging to escherichia coli, enterobacter cloacae, enterobacter aerogenes, clostridium difficile, bifidobacterium adolescentis, and b. longum. hbga expression of the bacteria as well as binding of human nov virus-like particles (vlps, gi.1, and gii.4 strains) to the bacteria were detected by flow ...	2015	26191052
clostridium difficile drug pipeline: challenges in discovery and development of new agents.	in the past decade clostridium difficile has become a bacterial pathogen of global significance. epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. in response to the increasing medical burden, a new c. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of c. difficile-associated diarrhea. rudimentary fecal transplants are also being trialed as effective treatments ...	2015	25760275
coxiella burnetii phagocytosis is regulated by gtpases of the rho family and the rhoa effectors mdia1 and rock.	the gtpases belonging to the rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. rock and mdia1 are downstream effectors of rhoa, a gtpase involved in that process. coxiella burnetii, the etiologic agent of q fever, is internalized by the host´s cells in an actin-dependent manner. nevertheless, the molecular mechanism involved in this process has been poorly characterized. this work analyzes the role of different gtpases of the rho fa ...	2015	26674774
cyclic digmp regulates production of sortase substrates of clostridium difficile and their surface exposure through zmpi protease-mediated cleavage.	in gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. in contrast to other gram-positive bacteria, only one single sortase enzyme, srtb, is conserved between strains of clostridium difficile. sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. here, we demonstrate the functionality of sortase in c. difficile. we identify two sortase-ancho ...	2015	26283789
dna sequence signatures for rapid detection of six target bacterial pathogens using pcr assays.	using streptococcus pyogenes as a model, we previously established a stepwise computational workflow to effectively identify species-specific dna signatures that could be used as pcr primer sets to detect target bacteria with high specificity and sensitivity. in this study, we extended the workflow for the rapid development of pcr assays targeting enterococcus faecalis, enterococcus faecium, clostridium perfringens, clostridium difficile, clostridium tetani, and staphylococcus aureus, which are ...	2015	26279626
structural and evolutionary analyses show unique stabilization strategies in the type iv pili of clostridium difficile.	type iv pili are produced by many pathogenic gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion, and horizontal gene transfer. however, many gram-positive species, including clostridium difficile, also produce type iv pili. here, we identify the major subunit of the type iv pili of c. difficile, pila1, and describe multiple 3d structures of pila1, demonstrating the diversity found in three strains of c. difficile. we also ...	2015	25599642
a catalytic dna activated by a specific strain of bacterial pathogen.	pathogenic strains of bacteria are known to cause various infectious diseases and there is a growing demand for molecular probes that can selectively recognize them. here we report a special dnazyme (catalytic dna), rfd-cd1, that shows exquisite specificity for a pathogenic strain of clostridium difficile (c. difficile). rfd-cd1 was derived by an in vitro selection approach where a random-sequence dna library was allowed to react with an unpurified molecular mixture derived from this strain of c ...	2015	26676768
increased toxin expression in a clostridium difficile mfd mutant.	the symptoms of clostridium difficile infection are mediated primarily by two toxins, tcda and tcdb, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. several global regulators have been implicated in the regulation of toxin expression, such as ccpa and cody.	2015	26679502
meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance.	human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in copenhagen, denmark, from nine cities in three world regions. an average of 18.6 gb (14.8 to 25.7 gb) of raw illumina paire ...	2015	26161690
ferric uptake regulator fur control of putative iron acquisition systems in clostridium difficile.	clostridium difficile is an anaerobic, gram-positive, spore-forming opportunistic pathogen and is the most common cause of hospital-acquired infectious diarrhea. although iron acquisition in the host is a key to survival of bacterial pathogens, high levels of intracellular iron can increase oxidative damage. therefore, expression of iron acquisition mechanisms is tightly controlled by transcriptional regulators. we identified a c. difficile homologue of the master bacterial iron regulator fur. u ...	2015	26148711
diversity and evolution in the genome of clostridium difficile.	clostridium difficile infection (cdi) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. in the last 2 decades, pcr- and sequence-based techniques, particularly whole-genome sequencing (wgs), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. c. difficile is taxonomically distinct from many other well-known ...	2015	26085550
excretion of host dna in feces is associated with risk of clostridium difficile infection.	clostridium difficile infection (cdi) is intricately linked to the health of the gastrointestinal tract and its indigenous microbiota. in this study, we assessed whether fecal excretion of host dna is associated with cdi development. assuming that shedding of epithelial cell increases in the inflamed intestine, we used human dna excretion as a marker of intestinal insult. whole-genome shotgun sequencing was employed to quantify host dna excretion and evaluate bacterial content in fecal samples c ...	2015	26090486
multiplex real-time pcr method for simultaneous identification and toxigenic type characterization of clostridium difficile from stool samples.	the aim of this study was to develop and validate a multiplex real-time pcr assay for simultaneous identification and toxigenic type characterization of clostridium difficile.	2015	25932438
clonalframeml: efficient inference of recombination in whole bacterial genomes.	recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. here we present clonalframeml, which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. clonalframeml can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. we find evidence ...	2015	25675341
gastrointestinal dysbiosis and the use of fecal microbial transplantation in clostridium difficile infection.	the impact of antibiotics on the human gut microbiota is a significant concern. antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. clostridium difficile infections (cdi) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. studies show that variability in the innate host response may in part impact upon cdi severit ...	2015	26600975
experience with cultivated microbiota transplant: ongoing treatment of clostridium difficile patients in sweden.		2015	26031676
fecal microbiota transplantation as novel therapy in gastroenterology: a systematic review.	to study the clinical efficacy and safety of fecal microbiota transplantation (fmt). we systematically reviewed fmt used as clinical therapy.	2015	25954111
extensive identification of bacterial riboflavin transporters and their distribution across bacterial species.	riboflavin, the precursor for the cofactors flavin mononucleotide (fmn) and flavin adenine dinucleotide, is an essential metabolite in all organisms. while the functions for de novo riboflavin biosynthesis and riboflavin import may coexist in bacteria, the extent of this co-occurrence is undetermined. the ribm, ribn, rfuabcd and the energy-coupling factor-ribu bacterial riboflavin transporters have been experimentally characterized. in addition, impx, rfnt and ribxy are proposed as riboflavin tr ...	2015	25938806
an assessment of antimicrobial resistant disease threats in canada.	antimicrobial resistance (amr) of infectious agents is a growing concern for public health organizations. given the complexity of this issue and how widespread the problem has become, resources are often insufficient to address all concerns, thus prioritization of amr pathogens is essential for the optimal allocation of risk management attention. since the epidemiology of amr pathogens differs between countries, country-specific assessments are important for the determination of national priorit ...	2015	25905797
effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent clostridium difficile infection.	clostridium difficile infection (cdi), a complication of antibiotic-induced injury to the gut microbiome, is a prevalent and dangerous cause of infectious diarrhea. antimicrobial therapy for cdi is typically effective for acute symptoms, but up to one third of patients later experience recurrent cdi. fecal-derived microbiota transplantation (fmt) can ameliorate the underlying dysbiosis and is highly effective for recurrent cdi. traditional methods of fmt are limited by patient discomfort, risk a ...	2015	25885020
fecal microbiota transplantation and successful resolution of multidrug-resistant-organism colonization.	we report a case in which fecal microbiota transplantation (fmt) utilized for relapsing clostridium difficile colitis successfully eradicated colonization with several multidrug-resistant organisms (mdros). fmt may have an additive benefit of reducing mdro carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyond c. difficile.	2015	25878340
complicated fecal microbiota transplantation in a tetraplegic patient with severe clostridium difficile infection.	a 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent clostridium difficile (c. difficile) infection subsequent to antibiotic treatment for pneumonia. after a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. four days subsequent to th ...	2015	25834343
fecal microbiota transplant protocol for clostridium difficile infection.	fecal microbiota transplant has become more acceptable as a therapeutic for recurrent clostridium difficile infection. the fda has an enforcement discretion policy for practitioner's performing this therapy, which includes informed consent for this experimental treatment. this manuscript describes a typical procedure that can be followed that includes the important aspects of this preparation and treatment.	2015	25805532
targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against clostridium difficile-associated disease.	clostridium difficile is a leading cause of death from gastrointestinal infections in north america. antibiotic therapy is effective, but the high incidence of relapse and the rise in hypervirulent strains warrant the search for novel treatments. surface layer proteins (slps) cover the entire c. difficile bacterial surface, are composed of high-molecular-weight (hmw) and low-molecular-weight (lmw) subunits, and mediate adherence to host cells. passive and active immunization against slps has enh ...	2015	25936376
a new lab developed real time pcr assay for direct detection of c. difficle from stool sample without dna extraction.	clostridium difficile is a major cause of nosocomial antibiotic-associated infectious diarrhea and pseudomembranous colitis. detection of c. difficile by anaerobic bacterial culture and/or cytotoxicity assays has been largely replaced by rapid enzyme immunoassays (eia). however, due to the lack of sensitivity of stool eia, we developed a multiplex real-time pcr assay targeting the c. difficile toxin genes tcdb. stool samples from hospitalized pediatric patients suspected of having c. difficile-a ...	2016	27829823
evaluation of luminex xtag gastrointestinal pathogen panel assay for detection of multiple diarrheal pathogens in fecal samples in vietnam.	diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. the diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. we evaluated the luminex xtag gastrointestinal pathogen p ...	2016	26865681