Publications

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the bacterial interactions in the nasopharynx of children receiving adenoidectomy.staphylococcus aureus, streptococcus pneumoniae, and haemophilus influenzae are the common pathogens that colonize in the nasopharynx of children. polymicrobial interactions are thought to play an important role in different sites throughout the human body. however, there are currently very few studies that investigate the interactions between s. aureus, s. pneumoniae, and h. influenzae in the nasopharynx. we retrospectively analyzed the adenoid tissue culture from 269 children who received aden ...201525705586
multi-serotype pneumococcal nasopharyngeal carriage prevalence in vaccine naïve nepalese children, assessed using molecular serotyping.invasive pneumococcal disease is one of the major causes of death in young children in resource poor countries. nasopharyngeal carriage studies provide insight into the local prevalence of circulating pneumococcal serotypes. there are very few data on the concurrent carriage of multiple pneumococcal serotypes. this study aimed to identify the prevalence and serotype distribution of pneumococci carried in the nasopharynx of young healthy nepalese children prior to the introduction of a pneumococc ...201525643355
importance of viruses in acute otitis media.acute otitis media occurs as a complication of viral upper respiratory tract infection. bacterial otopathogens and respiratory viruses interact and play important roles in acute otitis media development. a better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease.201525514574
clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype.the relationship between clinical phenotype of childhood primary ciliary dyskinesia (pcd) and ultrastructural defects and genotype is poorly defined.201525493340
superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults.distinguishing between bacterial and viral lower respiratory tract infection (lrti) remains challenging. transcriptional profiling is a promising tool for improving diagnosis in lrti.201525637350
microbiome changes in healthy volunteers treated with gsk1322322, a novel antibiotic targeting bacterial peptide deformylase.gsk1322322 is a novel antibacterial agent under development, and it has known antibacterial activities against multidrug-resistant respiratory and skin pathogens through its inhibition of the bacterial peptide deformylase. here, we used next-generation sequencing (ngs) of the bacterial 16s rrna genes from stool samples collected from 61 healthy volunteers at the predosing and end-of-study time points to determine the effects of gsk1322322 on the gastrointestinal (gi) microbiota in a phase i, ran ...201525487798
the relationship of c-reactive protein levels and positive culture with quality of life in acute rhinosinusitis.acute rhinosinusitis (ars) has been shown to significantly reduce patient quality of life (qol). while the qol in patients with chronic rhinosinusitis has been the subject of intensive research over the last decade, studies measuring the impact of ars on patient qol have remained relatively scarce. the aim of this study was to determine the relationship between the qol and parameters suggestive of acute bacterial rhinosinusitis (c-reactive protein [crp] levels and positive culture) and to see if ...201525670887
mortality in healthcare-associated pneumonia in a low resistance setting: a prospective observational study.the classification of pneumonia as community-acquired pneumonia (cap) or healthcare-associated pneumonia (hcap) has implications for selection of initial antimicrobial therapy. hcap has been associated with an increased prevalence of multidrug-resistant (mdr) pathogens and with high mortality leading to recommendations for broad empiric therapy.201525664503
aetiology of acute lower respiratory infections among children under five years in accra, ghana.the study aimed to investigate the aetiological agents and clinical presentations associated with acute lower respiratory infections (alri) among children under five years old at the korle-bu teaching hospital in ghana. this was a cross-sectional study carried from february to december 2001. nasopharyngeal aspirates and venous blood specimens obtained from 108 children with features suggestive of alri, were cultured and the isolated bacterial organisms were identified biochemically. nasopharynge ...201525629622
diagnosis and management of primary ciliary dyskinesia.primary ciliary dyskinesia (pcd) is a rare autosomal recessive disorder with defective structure and/or function of motile cilia/flagella, causing chronic upper and lower respiratory tract infections, fertility problems, and disorders of organ laterality. diagnosing pcd requires a combined approach utilizing characteristic phenotypes and complementary methods for detection of defects of ciliary function and ultrastructure, measurement of nasal nitric oxide and genetic testing. currently, biallel ...201525610612
the extracellular rna complement of escherichia coli.the secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. in bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. to date, released products, such as small molecules, dna, peptides, and proteins, have been well studied in bacteria. however, the bacterial extracellular rna complement has so far not been comprehensively characterized. here, ...201525611733
oropharyngeal colonization with neisseria lactamica, other nonpathogenic neisseria species and moraxella catarrhalis among young healthy children in ahvaz, iran.neisseria lactamica as one of the main commensal in oropharynx during the childhood is related to the induction of a natural immunity against meningococcal meningitis. also moraxella catarrhalis in oropharynx of children is a predisposing factor for otitis media infection.201525964847
etiology and antimicrobial susceptibility of middle ear fluid pathogens in costa rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the national immunization program: acute otitis media microbiology in costa rican children.acute otitis media (aom) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (pcv7) introduction in costa rica (private sector, 2004; national immunization program, 2009). this was a combined prospective and retrospective study conducted in a routine clinical setting in san josé, costa rica. in the prospective part of the study, which was conducted post-pcv7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serot ...201525590837
bilateral conjunctivitis in a returned traveller. 201525590460
culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age.the upper respiratory tract (urt) is a crucial site for host defense, as it is home to bacterial communities that both modulate host immune defense and serve as a reservoir of potential pathogens. young children are at high risk of respiratory illness, yet the composition of their urt microbiota is not well understood. microbial profiling of the respiratory tract has traditionally focused on culturing common respiratory pathogens, whereas recent culture-independent microbiome profiling can only ...201525575312
endophthalmitis: state of the art.endophthalmitis is an uncommon diagnosis but can have devastating visual outcomes. endophthalmitis may be endogenous or exogenous. exogenous endophthalmitis is caused by introduction of pathogens through mechanisms such as ocular surgery, open-globe trauma, and intravitreal injections. endogenous endophthalmitis occurs as a result of hematogenous spread of bacteria or fungi into the eye. these categories of endophthalmitis have different risk factors and causative pathogens, and thus require dif ...201525609911
validation of a new aspergillus real-time pcr assay for direct detection of aspergillus and azole resistance of aspergillus fumigatus on bronchoalveolar lavage fluid.azole resistance in aspergillus fumigatus is increasingly reported. here, we describe the validation of the aspergenius, a new multiplex real-time pcr assay consisting of two multiplex real-time pcrs, one that identifies the clinically relevant aspergillus species, and one that detects the tr34, l98h, t289a, and y121f mutations in cyp51a and differentiates susceptible from resistant a. fumigatus strains. the diagnostic performance of the aspergenius assay was tested on 37 bronchoalveolar lavage ...201525568431
chronic obstructive pulmonary disease and asthma-associated proteobacteria, but not commensal prevotella spp., promote toll-like receptor 2-independent lung inflammation and pathology.recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing gram-negative prevotella spp. however, the immunological properties of these bacteria in the respiratory system remain unknown. here we compare the innate respiratory immune response to three gram-negative commensal prevotella strains (prevotella melaninogenica, prevotella nanceiensis and prevotella salivae) and three gram-negative pathogenic proteobacteria known to colonize ...201525179236
entericidin is required for a probiotic treatment (enterobacter sp. strain c6-6) to protect trout from cold-water disease challenge.flavobacterium psychrophilum causes bacterial cold-water disease in multiple fish species, including salmonids. an autochthonous enterobacter strain (c6-6) inhibits the in vitro growth of f. psychrophilum, and when ingested as a putative probiotic, it provides protection against injection challenge with f. psychrophilum in rainbow trout. in this study, low-molecular-mass (≤3 kda) fractions from both enterobacter c6-6 and escherichia coli k-12 culture supernatants inhibited the growth of f. psych ...201525381243
acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats.one would assume that the anti-inflammatory activity of α1-anti-trypsin (aat) is the result of inhibiting neutrophil enzymes. however, aat exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade aat, is over-emphasized. non-obvious developments in ...201525351931
mechanisms of bacterial colonization of the respiratory tract.respiratory tract infections are an important cause of morbidity and mortality worldwide. chief among these are infections involving the lower airways. the opportunistic bacterial pathogens responsible for most cases of pneumonia can cause a range of local and invasive infections. however, bacterial colonization (or carriage) in the upper airway is the prerequisite of all these infections. successful colonizers must attach to the epithelial lining, grow on the nutrient-limited mucosal surface, e ...201526488280
compendium of pseudo conditions in sexually transmitted diseases. 201526392668
influence of pseudomonas aeruginosa on exacerbation in patients with bronchiectasis.a majority of the studies done on the western population have shown that pseudomonas aeruginosa causes many severe infections in patients with bronchiectasis as compared to other pathogens. there is scarcity of similar data from the asian population.201525722615
toward primary prevention of asthma. reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma.a first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (rsv) and rhinovirus (rv) lower respiratory tract infections (lrtis) being strongl ...201525369458
the microbiome in asthma.the application of recently developed sensitive, specific, culture-independent tools for identification of microbes is transforming concepts of microbial ecology, including concepts of the relationships between the vast complex populations of microbes associated with ourselves and with states of health and disease. although most work initially focused on the community of microbes (microbiome) in the gastrointestinal tract and its relationship to gastrointestinal disease, interest has expanded to ...201525567040
effects of vaccination with 10-valent pneumococcal non-typeable haemophilus influenza protein d conjugate vaccine (phid-cv) on the nasopharyngeal microbiome of kenyan toddlers.pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable haemophilus influenzae protein-d conjugate vaccine (phid-cv).201526083474
kingella kingae: carriage, transmission, and disease.kingella kingae is a common etiology of pediatric bacteremia and the leading agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. this gram-negative bacterium is carried asymptomatically in the oropharynx and disseminates by close interpersonal contact. the colonized epithelium is the source of bloodstream invasion and dissemination to distant sites, and certain clones show significant association with bacteremia, osteoarthritis, or endocarditis. kingella kingae produces ...201525567222
real-time detection of a virus using detection dogs.viral infections are ubiquitous in humans, animals, and plants. real-time methods to identify viral infections are limited and do not exist for use in harsh or resource-constrained environments. previous research identified that tissues produce unique volatile organic compounds (voc) and demonstrated that voc concentrations change during pathologic states, including infection, neoplasia, or metabolic disease. patterns of voc expression may be pathogen specific and may be associated with an odor ...201526779494
real-time detection of a virus using detection dogs.viral infections are ubiquitous in humans, animals, and plants. real-time methods to identify viral infections are limited and do not exist for use in harsh or resource-constrained environments. previous research identified that tissues produce unique volatile organic compounds (voc) and demonstrated that voc concentrations change during pathologic states, including infection, neoplasia, or metabolic disease. patterns of voc expression may be pathogen specific and may be associated with an odor ...201526779494
polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome.microbial aetiology of intensive care unit (icu)-acquired pneumonia (icuap) determines antibiotic treatment and outcomes. the impact of polymicrobial icuap is not extensively known. we therefore investigated the characteristics and outcomes of polymicrobial aetiology of icuap.201526703094
full genomic characterization of a saffold virus isolated in peru.while studying respiratory infections of unknown etiology we detected saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. the full viral genome recovered by deep sequencing showed 98% identity to a previously described saffold strain isolated in japan. phylogenetic analysis confirmed the peruvian saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in asia. this is the first docum ...201526610576
spectrophotometric investigations of macrolide antibiotics: a brief review.macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by streptomyces species. they belong to the polyketide class of natural products. their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. they are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. different analytical techniques have been reported for the determination of macrolides such a ...201526609215
real life management of community-acquired pneumonia in adults in the gulf region and comparison with practice guidelines: a prospective study.very few data exist on the management of community-acquired pneumonia (cap) in patients admitted to hospitals in the gulf region. the objectives of this study were to describe treatment patterns for cap in 38 hospitals in five gulf countries (united arab emirates, kuwait, bahrain, oman, and qatar) and to compare the findings to the most recent infectious diseases society of america (idsa)/american thoracic society (ats) guidelines.201526424530
clinical characteristics of nursing home-acquired pneumonia in elderly patients admitted to a korean teaching hospital.nursing home-acquired pneumonia (nhap) is included under healthcare-associated pneumonia. however, the optimal treatment strategy for nhap has been controversial in several studies. we evaluated the clinical features of nhap compared to community-acquired pneumonia (cap) in elderly patients admitted with pneumonia.201526354058
differentiation of acute q fever from other infections in patients presenting to hospitals, the netherlands(1).differentiating acute q fever from infections caused by other pathogens is essential. we conducted a retrospective case-control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for q fever. patients with acute q fever were younger and had higher c-reactive protein levels but lower leukocyte coun ...201526196955
profile of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections.tedizolid phosphate is the first once-daily oxazolidinone approved by the united states food and drug administration for the treatment of acute bacterial skin and skin structure infections (absssi). it is more potent in vitro than linezolid against methicillin-resistant staphylococcus aureus (mrsa) and other gram-positive pathogens causing absssi, even retaining activity against some linezolid-resistant strains. tedizolid is approximately 90% protein bound, leading to lower free-drug concentrati ...201525960671
bacteriological assessment of healthcare-associated pneumonia using a clone library analysis.the causative pathogens of healthcare-associated pneumonia (hcap) remain controversial, and the use of conventional cultivation of sputum samples is occasionally inappropriate due to the potential for oral bacterial contamination. it is also sometimes difficult to determine whether methicillin-resistant staphylococcus aureus (mrsa) is a true causative pathogen of hcap.201525874715
the burden and etiology of community-onset pneumonia in the aging japanese population: a multicenter prospective study.the increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. this study was conducted to elucidate the burden of community-onset pneumonia (cop) and its etiologic fractions in japan, the world's most aged society.201525822890
etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in norway.despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (cap) is still not well described. we applied polymerase chain reaction (pcr) and conventional methods to describe etiology of cap in hospitalized adults and evaluated their respective diagnostic yields.201525887603
colistin for lung infection: an update.increasing incidence of resistance of gram-negative bacteria against even newer antibiotic including carbapenem has generated interest in the old antibiotic colistin, which are being used as salvage therapy in the treatment of multidrug resistant infection. colistin has excellent bactericidal activity against most gram-negative bacilli. it has shown persist level in the liver, kidney, heart, and muscle; while it is poorly distributed to the bones, cerebrospinal fluid, lung parenchyma, and pleura ...201525705428
abundant intergenic taactga direct repeats and putative alternate rna polymerase β' subunits in marine beggiatoaceae genomes: possible regulatory roles and origins.the genome sequences of several giant marine sulfur-oxidizing bacteria present evidence of a possible post-transcriptional regulatory network that may have been transmitted to or from two distantly related bacteria lineages. the draft genome of a cand. "maribeggiatoa" filament from the guaymas basin (gulf of california, mexico) seafloor contains 169 sets of taactga direct repeats and one indirect repeat, with two to six copies per set. related heptamers are rarely or never found as direct repeat ...201526733950
whole-genome sequencing targets drug-resistant bacterial infections.during the past two decades, the technological progress of whole-genome sequencing (wgs) had changed the fields of environmental microbiology and biotechnology, and, currently, is changing the underlying principles, approaches, and fundamentals of public health, epidemiology, health economics, and national productivity. today's wgs technologies are able to compete with conventional techniques in cost, speed, accuracy, and resolution for day-to-day control of infectious diseases and outbreaks in ...201526243131
procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream infections.procalcitonin (pct) can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. the aim of this study was to evaluate pct diagnostic accuracy in discriminating gram-positive, gram-negative, and fungal bloodstream infections. a total of 1,949 samples from patients with suspected bloodstream infections were included in the study. median pct value in gram-negative (13.8 ng/ml, interquartile range (iqr) 3.4-44.1) bacteremias was significantly highe ...201525852221
diagnostic value of bronchoalveolar lavage in leukemic and bone marrow transplant patients: the impact of antimicrobial therapy.there is significant morbidity and mortality from pneumonia in leukemic and bone marrow transplant patients. we sought to explore the diagnostic yield of bronchoalveolar lavage (bal) in these patients with new pulmonary infiltrates. a retrospective chart review of approximately 200 non- human immunodeficiency virus (hiv) leukemic and hematopoietic stem cell transplantation (hsct) patients who underwent bronchoscopy at a single academic cancer center was performed. antimicrobial use for less than ...201525574361
metagenomic human repiratory air in a hospital environment.hospital-acquired infection (hai) or nosocomial infection is an issue that frequent hospital environment. we believe conventional regulated petri dish method is insufficient to evaluate hai. to address this problem, metagenomic sequencing was applied to screen airborne microbes in four rooms of beijing hospital. with air-in amount of sampler being setup to one person's respiration quantity, metagenomic sequencing identified huge numbers of species in the rooms which had already qualified widely ...201526431488
contact-dependent growth inhibition (cdi) and cdib/cdia two-partner secretion proteins.bacteria have developed several strategies to communicate and compete with one another in complex environments. one important mechanism of inter-bacterial competition is contact-dependent growth inhibition (cdi), in which gram-negative bacteria use cdib/cdia two-partner secretion proteins to suppress the growth of neighboring target cells. cdib is an omp85 outer-membrane protein that exports and assembles cdia exoproteins onto the inhibitor cell surface. cdia binds to receptors on susceptible ba ...201526388411
antibacterial effects of cinnamon: from farm to food, cosmetic and pharmaceutical industries.herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. moreover, due to the growing d ...201526378575
development of two real-time multiplex pcr assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections.the frequent lack of a positive and timely microbiological diagnosis in patients with lower respiratory tract infection (lrti) is an important obstacle to antimicrobial stewardship. patients are typically prescribed broad-spectrum empirical antibiotics while microbiology results are awaited, but, because these are often slow, negative, or inconclusive, de-escalation to narrow-spectrum agents rarely occurs in clinical practice. the aim of this study was to develop and evaluate two multiplex real- ...201525980353
impact of the cftr-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a g551d mutation.airway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (cf), an autosomal genetic disorder caused by mutation in the cf transmembrane conductance regulator (cftr). recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the g551d-mutated cftr, allowing significant improvement in lung function.201525853698
mannose-binding lectin protein and its association to clinical outcomes in copd: a longitudinal study.functional deficiency of mannose-binding lectin (mbl) may contribute to the pathogenesis of chronic obstructive pulmonary disease. we hypothesized that specific mbl2 gene polymorphisms and circulating mbl protein levels are associated with clinically relevant outcomes in the predicting outcome using systemic markers in severe exacerbations of copd promise-copd cohort.201526684757
comparison of serum procalcitonin in respiratory infections and bloodstream infections.this study observed the relationship between procalcitonin (pct) and results of sputum culture, the relationship between pct and results of blood culture to evaluate and compare the value of pct in respiratory and bloodstream infections.201526885109
multicenter evaluation of the bruker maldi biotyper ca system for the identification of clinical aerobic gram-negative bacterial isolates.the prompt and accurate identification of bacterial pathogens is fundamental to patient health and outcome. recent advances in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) have revolutionized bacterial identification in the clinical laboratory, but uniform incorporation of this technology in the u.s. market has been delayed by a lack of fda-cleared systems. in this study, we conducted a multicenter evaluation of the maldi biotyper ca (mbt-ca) system ...201526529504
diagnosis, monitoring, and treatment of primary ciliary dyskinesia: pcd foundation consensus recommendations based on state of the art review.primary ciliary dyskinesia (pcd) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. many physicians incorrectly diagnose pcd or eliminate pcd from their differential diagnosis due to inexperience with diagnostic testing methods. thus far, all therapies used for pcd are unproven through large clinical trials. this review article outlines consensus recommendations from pcd physicians in north america who have been engaged ...201526418604
diagnosis, monitoring, and treatment of primary ciliary dyskinesia: pcd foundation consensus recommendations based on state of the art review.primary ciliary dyskinesia (pcd) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. many physicians incorrectly diagnose pcd or eliminate pcd from their differential diagnosis due to inexperience with diagnostic testing methods. thus far, all therapies used for pcd are unproven through large clinical trials. this review article outlines consensus recommendations from pcd physicians in north america who have been engaged ...201526418604
determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease.changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (aecopd), including patterns of bacteriological relapse and superinfection are not well understood. sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. bacterial eradicatio ...201526370552
determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease.changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (aecopd), including patterns of bacteriological relapse and superinfection are not well understood. sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. bacterial eradicatio ...201526370552
meropenem population pharmacokinetics in critically ill patients with septic shock and continuous renal replacement therapy: influence of residual diuresis on dose requirements.meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (crrt) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. this multicenter study aimed to describe the pharmacokinetics (pks) of meropenem in this population to identify the sources of pk variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. thirty patients with septic shock and crrt ...201526124172
infection control in the pulmonary function test laboratory.pulmonary function testing plays a crucial role in the diagnostic evaluation of patients with lung diseases. cases of cross infection acquired from the pulmonary function laboratory, although rare, have been reported from various countries. it is therefore imperative to identify the risks and potential organisms implicated in cross infections in a pulmonary function test (pft) laboratory and implement better and more effective infection control procedures, which will help in preventing cross inf ...201526180386
the microbiome of the human lower airways: a next generation sequencing perspective.for a long time, the human lower airways were considered a sterile environment where the presence of microorganisms, typically revealed by culturing, was interpreted as an abnormal health state. more recently, high-throughput sequencing-based studies have led to a shift in this perception towards the notion that even in healthy conditions the lower airways show either transient presence or even permanent colonization by microorganisms. however, challenges related to low biomass and contamination ...201526140078
aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections.the antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. a series of n-benzyl-substituted 3'-(r)-3'-aminomethyl-3'-hydroxy spectinomycins was developed on the basis of a computational analysis of the aminomethyl spectinomycin binding site and structure-guided synthesis. these compounds had ribosomal inhibition values comparable ...201525995221
bacterial adaptation during chronic respiratory infections.chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (cf) and chronic obstructive pulmonary disease (copd). the process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. these adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient de ...201525738646
contribution of the bact/alert mb mycobacterium bottle to bloodstream infection surveillance in thailand: added yield for burkholderia pseudomallei.community-acquired bloodstream infections cause substantial morbidity and mortality worldwide, but microbiology capacity and surveillance limitations have challenged good descriptions of pathogen distribution in many regions, including southeast asia. active surveillance for bloodstream infections has been conducted in two rural thailand provinces for >7 years. blood specimens were divided into two culture bottles, one optimized for aerobic growth (f bottle) and a second for enhanced growth of m ...201525588650
identification of chemical compounds that inhibit the function of glutamyl-trna synthetase from pseudomonas aeruginosa.pseudomonas aeruginosa glutamyl-trna synthetase (glurs) was overexpressed in escherichia coli. sequence analysis indicated that p. aeruginosa glurs is a discriminating glurs and, similar to other glurs proteins, requires the presence of trna(glu) to produce a glutamyl-amp intermediate. kinetic parameters for interaction with trna were determined and the k(cat) and km were 0.8 s(-1) and 0.68 µm, respectively, resulting in a k(cat)/km of 1.18 s(-1) µm(-1). a robust aminoacylation-based scintillati ...201526116192
high throughput screen identifies natural product inhibitor of phenylalanyl-trna synthetase from pseudomonas aeruginosa and streptococcus pneumoniae.pseudomonas aeruginosa and streptococcus pneumoniae are causative agents in a wide range of infections. genes encoding proteins corresponding to phenylalanyl-trna synthetase (phers) were cloned from both bacteria. the two forms of phers were kinetically evaluated and the k(m)'s for p. aeruginosa phers with its three substrates, phenylalanine, atp and trna(phe) were determined to be 48, 200, and 1.2 µm, respectively, while the k(m)'s for s. pneumoniae phers with respect to phenylalanine, atp and ...201525601215
ralstonia solanacearum uses inorganic nitrogen metabolism for virulence, atp production, and detoxification in the oxygen-limited host xylem environment.genomic data predict that, in addition to oxygen, the bacterial plant pathogen ralstonia solanacearum can use nitrate (no3(-)), nitrite (no2(-)), nitric oxide (no), and nitrous oxide (n2o) as terminal electron acceptors (teas). genes encoding inorganic nitrogen reduction were highly expressed during tomato bacterial wilt disease, when the pathogen grows in xylem vessels. direct measurements found that tomato xylem fluid was low in oxygen, especially in plants infected by r. solanacearum. xylem f ...201525784703
time for a change: addressing r&d and commercialization challenges for antibacterials.the antibacterial therapeutic area has been described as the perfect storm. resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. this paper examine ...201525918443
association of targeted multiplex pcr with resequencing microarray for the detection of multiple respiratory pathogens.a large number of viral and bacterial organisms are responsible for community-acquired pneumonia (cap) which contributes to substantial burden on health management. a new resequencing microarray (rpm-ivdc1) associated with targeted multiplex pcr was recently developed and validated for multiple respiratory viruses detection and discrimination. in this study, we evaluated the capability of rpm-ivdc1 for simultaneous identification of multiple viral and bacterial organisms. the nasopharyngeal aspi ...201526074910
pathogens protection against the action of disinfectants in multispecies biofilms.biofilms constitute the prevalent way of life for microorganisms in both natural and man-made environments. biofilm-dwelling cells display greater tolerance to antimicrobial agents than those that are free-living, and the mechanisms by which this occurs have been investigated extensively using single-strain axenic models. however, there is growing evidence that interspecies interactions may profoundly alter the response of the community to such toxic exposure. in this paper, we propose an overvi ...201526236291
discrepancy in maldi-tof ms identification of uncommon gram-negative bacteria from lower respiratory secretions in patients with cystic fibrosis.early identification of microbial organisms from respiratory secretions of patients with cystic fibrosis (cf) is important to guide therapeutic decisions. the objective was to compare the accuracy of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (maldi-tof ms) relative to the conventional phenotypic method in identifying common bacterial isolates, including nonfermenting gram-negative bacteria, in a cohort of patients with cf.201525995646
performances and reliability of bruker microflex lt and vitek ms maldi-tof mass spectrometry systems for the identification of clinical microorganisms.in clinical microbiology laboratories, routine microbial identification is mostly performed using culture based methodologies requiring 24 to 72 hours from culturing to identification. matrix assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) technology has been established as a cost effective, reliable, and faster alternative identification platform. in this study, we evaluated the reliability of the two available maldi-tof ms systems for their routine clinical ...201526793718
empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures.the purpose of this investigation was to explore the presumed relationship between the days of hospitalisation and microorganisms identified by endotracheal aspirate cultures in relation to adequate empirical treatment strategies of pneumonia in the intensive care unit (icu). all potentially pathogenic microorganisms identified by (surveillance) cultures of endotracheal aspirates obtained in the icus of two dutch teaching hospitals in 2007 and 2012 were retrospectively collected and analysed. an ...201526385348
pneumonia in the neutropenic cancer patient.pneumonia is the leading cause of death among neutropenic cancer patients, particularly those with acute leukaemia. even with empiric therapy, case fatality rates of neutropenic pneumonias remain unacceptably high. however, recent advances in the management of neutropenic pneumonia offer hope for improved outcomes in the cancer setting. this review summarizes recent literature regarding the clinical presentation, microbiologic trends, diagnostic advances and therapeutic recommendations for cance ...201525784246
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
ccl20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to brucella abortus infection.both ccl20 and human β-defensin 2 (hbd2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. they are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. whereas brucella spp. can infect humans through inhalation, their ability to induce ccl20 and hbd2 in lung cells is unknown. here we show that b. abortus induces ccl20 expression in human alveolar (a549) or bronchial (calu-6) epithelial cell lines, primary alveo ...201526448160
the impact of immunosenescence on pulmonary disease.the global population is aging with significant gains in life expectancy particularly in the developed world. consequently, greater focus on understanding the processes that underlie physiological aging has occurred. key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. immunosenescence and its associated chronic low grade systemic "inflamm-aging" contribute to the development and progression of ...201526199462
moonlighting o-acetylserine sulfhydrylase: new functions for an old protein.o-acetylserine sulfhydrylase a (cysk) is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes the final reaction of cysteine biosynthesis in bacteria. cysk was initially identified in a complex with serine acetyltransferase (cyse), which catalyzes the penultimate reaction in the synthetic pathway. this "cysteine synthase" complex is stabilized by insertion of the cyse c-terminus into the active-site of cysk. remarkably, the cysk/cyse binding interaction is conserved in most bacterial and p ...201525731080
common cell shape evolution of two nasopharyngeal pathogens.respiratory infectious diseases are the third cause of worldwide death. the nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as neisseria meningitidis and moraxella catarrhalis. these microbes possess several surface structures that interact with the actors of the innate immune system. in our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences ...201526162030
adhesins involved in attachment to abiotic surfaces by gram-negative bacteria.during the first step of biofilm formation, initial attachment is dictated by physicochemical and electrostatic interactions between the surface and the bacterial envelope. depending on the nature of these interactions, attachment can be transient or permanent. to achieve irreversible attachment, bacterial cells have developed a series of surface adhesins promoting specific or nonspecific adhesion under various environmental conditions. this article reviews the recent advances in our understandi ...201526350310
the relationship between extensively drug-resistant tuberculosis and multidrug-resistant gram-negative bacilli.the relationship between extensively drug-resistant tuberculosis (xdr-tb) and multidrug-resistant gram-negative bacilli (mdr-gnb) is unclear. identification of the relationship between xdr-tb and mdr-gnb would have important implications for patient care.201526230499
proteomics of aggregatibacter actinomycetemcomitans outer membrane vesicles.aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. outer membrane vesicles (omvs) released by this species have been demonstrated to deliver effector proteins such as cytolethal distending toxin (cdt) and leukotoxin (ltxa) into human host cells and to act as triggers of innate immunity upon carriage of nod1- and nod2-active pathogen-associated molecular patterns (pamps). to improve our understanding of t ...201526381655
haemophilus influenzae: using comparative genomics to accurately identify a highly recombinogenic human pathogen.haemophilus influenzae is an opportunistic bacterial pathogen that exclusively colonises humans and is associated with both acute and chronic disease. despite its clinical significance, accurate identification of h. influenzae is a non-trivial endeavour. h. haemolyticus can be misidentified as h. influenzae from clinical specimens using selective culturing methods, reflecting both the shared environmental niche and phenotypic similarities of these species. on the molecular level, frequent geneti ...201526311542
aptamers against pathogenic microorganisms.an important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. one of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. the present review summarizes va ...201526258445
aptamers against pathogenic microorganisms.an important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. one of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. the present review summarizes va ...201526258445
development of a multilocus sequence typing scheme for molecular typing of mycoplasma pneumoniae.mycoplasma pneumoniae is a major human respiratory pathogen causing both upper and lower respiratory disease in humans of all ages, and it can also result in other serious extrapulmonary sequelae. a multilocus sequence typing (mlst) scheme for m. pneumoniae was developed based on the sequences of eight housekeeping genes (ppa, pgm, gyrb, gmk, glya, atpa, arcc, and adk) and applied to 55 m. pneumoniae clinical isolates and the two type strains m129 and fh. a total of 12 sequence types (sts) resul ...201526202118
structural basis of transcription inhibition by cbr hydroxamidines and cbr pyrazoles.cbr hydroxamidines are small-molecule inhibitors of bacterial rna polymerase (rnap) discovered through high-throughput screening of synthetic-compound libraries. cbr pyrazoles are structurally related rnap inhibitors discovered through scaffold hopping from cbr hydroxamidines. cbr hydroxamidines and pyrazoles selectively inhibit gram-negative bacterial rnap and exhibit selective antibacterial activity against gram-negative bacteria. here, we report crystal structures of the prototype cbr hydroxa ...201526190576
biological properties of extracellular vesicles and their physiological functions.in the past decade, extracellular vesicles (evs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. this is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. while intensive investigation has targeted the role of evs in different pathological processes, for example, in cancer and autoimmune diseases, the ev-mediated ...201525979354
moraxella catarrhalis acrab-oprm efflux pump contributes to antimicrobial resistance and is enhanced during cold shock response.moraxella catarrhalis is a common pathogen of the human respiratory tract. multidrug efflux pumps play a major role in antibiotic resistance and virulence in many gram-negative organisms. in the present study, the role of the acrab-oprm efflux pump in antibiotic resistance was investigated by constructing mutants that lack the acra, acrb, and oprm genes in m. catarrhalis strain o35e. we observed a moderate (1.5-fold) decrease in the mics of amoxicillin and cefotaxime and a marked (4.7-fold) decr ...201525583725
fine mapping of the interaction between c4b-binding protein and outer membrane proteins liga and ligb of pathogenic leptospira interrogans.the complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. leptospirosis is a worldwide zoonosis caused by spirochetes from the genus leptospira. pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors factor h [fh] and c4b-binding protein (c4bp) while non-patho ...201526517116
development of a new real-time pcr system for simultaneous detection of bacteria and fungi in pathological samples.a novel system for simultaneous detection of pathogenic bacteria and fungi in pathological samples was developed using a real-time polymerase chain reaction (pcr) system. this system, designated the "multi-microbial real-time pcr", has the potential to simultaneously detect 68 bacterial and 9 fungal species in a 96-well plate format. all probe-primer sets were designed to produce amplicons smaller than 210 bp using formalin-fixed paraffin-embedded samples as input. the specificity and sensitivit ...201526823918
dna microarray characterization of pathogens associated with sexually transmitted diseases.this study established a multiplex pcr-based microarray to detect simultaneously a diverse panel of 17 sexually transmitted diseases (stds)-associated pathogens including neisseria gonorrhoeae, chlamydia trachomatis, mycoplasma genitalium, mycoplasma hominis, ureaplasma, herpes simplex virus (hsv) types 1 and 2, and human papillomavirus (hpv) types 6, 11, 16, 18, 31, 33, 35, 39, 54 and 58. the target genes are 16s rrna gene for n. gonorrhoeae, m. genitalium, m. hominism, and ureaplasma, the majo ...201526208181
biofilm models of polymicrobial infection.interactions between microbes are complex and play an important role in the pathogenesis of infections. these interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. an increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. here w ...201526592098
the influence of smoking on the peri-implant microbiome.smokers are at high risk for 2 bacterially driven oral diseases: peri-implant mucositis and peri-implantitis. therefore, the purpose of this investigation was to use a deep-sequencing approach to identify the effect of smoking on the peri-implant microbiome in states of health and disease. peri-implant biofilm samples were collected from 80 partially edentulous subjects with peri-implant health, peri-implant mucositis, and peri-implantitis. bacterial dna was isolated and 16s ribsomal rna gene li ...201526124222
a modified shuttle plasmid facilitates expression of a flavin mononucleotide-based fluorescent protein in treponema denticola atcc 35405.oral pathogens, including treponema denticola, initiate the dysregulation of tissue homeostasis that characterizes periodontitis. however, progress of research on the roles of t. denticola in microbe-host interactions and signaling, microbial communities, microbial physiology, and molecular evolution has been hampered by limitations in genetic methodologies. this is typified by an extremely low transformation efficiency and inability to transform the most widely studied t. denticola strain with ...201526162875
the role of the local microbial ecosystem in respiratory health and disease.respiratory tract infections are a major global health concern, accounting for high morbidity and mortality, especially in young children and elderly individuals. traditionally, highly common bacterial respiratory tract infections, including otitis media and pneumonia, were thought to be caused by a limited number of pathogens including streptococcus pneumoniae and haemophilus influenzae. however, these pathogens are also frequently observed commensal residents of the upper respiratory tract (ur ...201526150660
outer membrane vesicles - offensive weapons or good samaritans?outer membrane vesicles (omvs) from gram-negative bacteria were first considered as artifacts and were followed with disbelief and bad reputation. later, their existence was accepted and they became characterized as bacterial bombs, virulence bullets, and even decoys. today, we know that omvs also can be involved in cell-cell signaling/communication and be mediators of immune regulation and cause disease protection. furthermore, omvs represent a distinct bacterial secretion pathway selecting and ...201525840612
development of real-time pcr assays for the detection of moraxella macacae associated with bloody nose syndrome in rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques.moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. the aim of this study was to develop specific molecular diagnostic assays for m. macacae and to determine their performance characteristics.201526365904
individuality, phenotypic differentiation, dormancy and 'persistence' in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology.for bacteria, replication mainly involves growth by binary fission. however, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically 'nonculturable' on media that normally admit their growth. they thereby evade detection by conventional culture-based methods. such dormant cells may also be observed in laboratory cultures and in clinical microbiology. they are usually more tolerant to s ...201526629334
comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections.uncomplicated skin and skin structure infections (usssis) are a common clinical problem. majority are caused by staphylococci and streptococci. different oral antibiotics are used for usssi, with comparable efficacy but varying treatment duration, cost, and adverse event profile. azithromycin is used in usssi in adults conventionally in a dose of 500 mg once for 5 days. the extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g do ...201526288467
moraxella catarrhalis binds plasminogen to evade host innate immunity.several bacterial species recruit the complement regulators c4b-binding protein, factor h, and vitronectin, resulting in resistance against the bactericidal activity of human serum. it was recently demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades c3b and c5. in this study, we found that a series of clinical isolates (n = 58) of the respiratory pathogen moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic ob ...201526099590
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