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using the electronic nose to identify airway infection during copd exacerbations.the electronic nose (e-nose) detects volatile organic compounds (vocs) in exhaled air. we hypothesized that the exhaled vocs print is different in stable vs. exacerbated patients with chronic obstructive pulmonary disease (copd), particularly if the latter is associated with airway bacterial infection, and that the e-nose can distinguish them.201526353114
clinical characteristics of protracted bacterial bronchitis in chinese infants.protracted bacterial bronchitis (pbb) is the common cause of chronic cough in children worldwide, but its etiology has not been fully recognized in china. we retrospectively investigated a total of 66 hospitalized infants under the age of three years with chronic wet cough enrolled in the affiliated children's hospital of soochow university from october 2010 to march 2014. all patients underwent bronchoscopy and broncho-alveolar lavage (bal) samples were processed for microbiological and cytolog ...201526338462
the potential impact of pneumococcal conjugate vaccine in africa: considerations and early lessons learned from the south african experience.the introduction of pneumococcal conjugate vaccine (pcv) into the south african public immunization program since 2009 adopted a novel vaccination schedule of 3 doses at 6, 14 and 40 weeks of age. over the past 5 y it has been shown that infant pcv immunization in south africa is effective in reducing the burden of invasive pneumococcal disease (ipd) among hiv-infected and hiv-uninfected children. furthermore, indirect protection of unvaccinated age-groups (including high risk groups such as hiv ...201526317537
the potential impact of pneumococcal conjugate vaccine in africa: considerations and early lessons learned from the south african experience.the introduction of pneumococcal conjugate vaccine (pcv) into the south african public immunization program since 2009 adopted a novel vaccination schedule of 3 doses at 6, 14 and 40 weeks of age. over the past 5 y it has been shown that infant pcv immunization in south africa is effective in reducing the burden of invasive pneumococcal disease (ipd) among hiv-infected and hiv-uninfected children. furthermore, indirect protection of unvaccinated age-groups (including high risk groups such as hiv ...201526317537
vaccine targets against moraxella catarrhalis.moraxella catarrhalis is a prominent pathogen that causes acute otitis media in children and lower respiratory tract infections in adults, resulting in a significant socioeconomic burden on healthcare systems globally. no vaccine is currently available for m. catarrhalis. promising m. catarrhalis target antigens have been characterized in animal models and should soon enter human clinical trials.201526565427
vaccine targets against moraxella catarrhalis.moraxella catarrhalis is a prominent pathogen that causes acute otitis media in children and lower respiratory tract infections in adults, resulting in a significant socioeconomic burden on healthcare systems globally. no vaccine is currently available for m. catarrhalis. promising m. catarrhalis target antigens have been characterized in animal models and should soon enter human clinical trials.201526565427
in vitro evaluation of the comprehensive antimicrobial and antioxidant properties of curtisia dentata (burm.f) c.a. sm: toxicological effect on the human embryonic kidney (hek293) and human hepatocellular carcinoma (hepg2) cell lines.curtisia dentata is used in african traditional medicine to treat variety of infections. c. dentata leaves were collected from buffelskloof nature reserve, south africa. the ethanol, chloroform, ethyl acetate and acetone extracts were evaluated for antimicrobial activity using micro dilution assay against escherichia coli, pseudomonas aeruginosa, mycobacterium smegmatis, mycoplasma hominis, candida albicans and some clinical isolates of moraxella catarrhalis, proteus mirabilis and staphylococcus ...201527065768
virus-induced secondary bacterial infection: a concise review.respiratory diseases are a very common source of morbidity and mortality among children. health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. the reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. the aim of this review is to update the current evidence on the virus-induced bacterial infection. we present several clinical as well in vitro studies that support the ...201526345407
quantitative analysis of pathogens in the lower respiratory tract of patients with chronic obstructive pulmonary disease.bacterial infection of the lower respiratory tract is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (copd) and acute exacerbations of copd (aecopd). this study investigates the potential relationship between aecopd and the load of six common bacterial pathogens in the lower respiratory tract using real-time quantitative pcr (rt-qpcr) in copd patients.201526286268
ceftobiprole for the treatment of pneumonia: a european perspective.ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in vitro activity against a number of gram-positive pathogens, including methicillin-resistant staphylococcus aureus and penicillin-resistant streptococcus pneumoniae, and gram-negative pathogens associated with hospital-acquired pneumonia (hap) and community-acquired pneumonia (cap). ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to ceftriaxone with or without linezolid in ...201526316697
impacts of the 13-valent pneumococcal conjugate vaccine in children.applications of the heptavalent pneumococcal conjugate vaccine (pcv7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. however, increased infections caused by non-pcv7 serotypes have been reported by several groups. to overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. the 13-valent pneumococcal conjugate vacci ...201526351648
nasopharyngeal bacterial carriage in the conjugate vaccine era with a focus on pneumococci.seven-valent pneumococcal conjugate vaccine (pcv7) was included in the uk national immunisation program in 2006, and this was replaced by thirteen-valent pcv in 2010. during this time, the carriage of vaccine-type streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type s. pneumoniae. carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive di ...201526351646
integrating microbial and host transcriptomics to characterize asthma-associated microbial communities.the relationships between infections in early life and asthma are not completely understood. likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. a number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-proteobacteria including haemophilus influenzae, moraxella catarrhalis, and firmicutes such as streptococcus pneumoniae. the aim of this study was to present a new approach that comb ...201526277095
16s rrna gene sequence-based identification of bacteria in automatically incubated blood culture materials from tropical sub-saharan africa.the quality of microbiological diagnostic procedures depends on pre-analytic conditions. we compared the results of 16s rrna gene pcr and sequencing from automatically incubated blood culture materials from tropical ghana with the results of cultural growth after automated incubation.201526270631
increased peripheral blood pro-inflammatory/cytotoxic lymphocytes in children with bronchiectasis.bronchiectasis (be) in children is common in some communities including indigenous children in australia. relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: t-cells, natural killer (nk) cells and nkt-like cells. we have shown that these cells produce increased cytotoxic (granzyme b and perforin) and inflammatory (ifnγ and tnfα) mediators in several adult chronic lung di ...201526258716
the efficacy of qingfengganke granule in treating postinfectious cough in pathogenic wind invading lungs syndrome: a multicenter, randomized, double-blind, placebo-controlled trial.postinfectious cough (pic) significantly affects cough-related quality of life but still lacks effective treatments. this study aims to investigate the efficacy of qingfengganke granule (qfgkg) in treating pic induced by pathogenic wind invading lungs syndrome.201526257822
periodontal status and oral health behavior in hospitalized patients with chronic obstructive pulmonary disease.we evaluated the periodontal health status and oral health behavior among hospitalized patients with chronic obstructive pulmonary disease (copd) to assess the association of copd with dental health.201526604629
factors affecting staphylococcus aureus colonization of the nasopharynx in the first 6 months of life.staphylococcal aureus (sa) colonization in early infancy is common, but the pattern and factors affecting its acquisition and persistence in the first few months of life are not well studied. the aim is to study the rate of sa nasopharyngeal (np) colonization at monthly intervals in the first 6 months of life and its association with environmental and host factors and other pathogenic np bacteria.201525961891
real-time microbiology laboratory surveillance system to detect abnormal events and emerging infections, marseille, france.infectious diseases are a major threat to humanity, and accurate surveillance is essential. we describe how to implement a laboratory data-based surveillance system in a clinical microbiology laboratory. two historical microsoft excel databases were implemented. the data were then sorted and used to execute the following 2 surveillance systems in excel: the bacterial real-time laboratory-based surveillance system (balyses) for monitoring the number of patients infected with bacterial species iso ...201526196165
prevalence and resistance pattern of moraxella catarrhalis in community-acquired lower respiratory tract infections.moraxella catarrhalis previously considered as commensal of upper respiratory tract has gained importance as a pathogen responsible for respiratory tract infections. its beta-lactamase-producing ability draws even more attention toward its varying patterns of resistance.201526261422
a year of infection in the intensive care unit: prospective whole genome sequencing of bacterial clinical isolates reveals cryptic transmissions and novel microbiota.bacterial whole genome sequencing holds promise as a disruptive technology in clinical microbiology, but it has not yet been applied systematically or comprehensively within a clinical context. here, over the course of one year, we performed prospective collection and whole genome sequencing of nearly all bacterial isolates obtained from a tertiary care hospital's intensive care units (icus). this unbiased collection of 1,229 bacterial genomes from 391 patients enables detailed exploration of se ...201526230489
cdia promotes receptor-independent intercellular adhesion.cdib/cdia proteins mediate inter-bacterial competition in a process termed contact-dependent growth inhibition (cdi). filamentous cdia exoproteins extend from cdi(+) cells and bind specific receptors to deliver toxins into susceptible target bacteria. cdi has also been implicated in auto-aggregation and biofilm formation in several species, but the contribution of cdia-receptor interactions to these multi-cellular behaviors has not been examined. using escherichia coli isolate ec93 as a model, w ...201526135212
long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.previously, the fiji pneumococcal project (fipp) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (pcv7 and 23vppv, respectively). immune hyporesponsiveness was observed in children vaccinated with 23vppv at 12 months of age compared with children who did not receive 23vppv. here we assess the long-term impact of 23vppv vaccination on nasopharyngeal carriage rates and densities of streptococcus pneumoniae, haemophilus in ...201526232540
association of prevalence of rhinitis, atopic eczema, rhinoconjunctivitis and wheezing with mortality from infectious diseases and with antibiotic susceptibility at a country level.it was previously reported that there is a positive correlation between incidence of type 1 diabetes and prevalence of asthma and atopic eczema. a negative correlation between the prevalence of type 1 diabetes and mortality from infectious diseases as well as a positive correlation with antibiotic susceptibility at a country level have also been reported.201526240791
a biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable haemophilus influenzae.non-typeable haemophilus influenzae contains an n(6)-adenine dna-methyltransferase (moda) that is subject to phase-variable expression (random on/off switching). five moda alleles, moda2, moda4, moda5, moda9 and moda10, account for over two-thirds of clinical otitis media isolates surveyed. here, we use single molecule, real-time (smrt) methylome analysis to identify the dna-recognition motifs for all five of these moda alleles. phase variation of these alleles regulates multiple proteins includ ...201526215614
vesicles-mediated resistance to antibiotics in bacteria. 201526257725
virulence of group a streptococci is enhanced by human complement inhibitors.streptococcus pyogenes, also known as group a streptococcus (gas), is an important human bacterial pathogen that can cause invasive infections. once it colonizes its exclusively human host, gas needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. several strains of gas bind to human-specific complement inhibitors, c4b-binding protein (c4bp) and/or factor h (fh), to curtail complement c3 (a critical opsonin) deposition. thi ...201526200783
validation of sensititre dry-form broth microdilution panels for susceptibility testing of ceftazidime-avibactam, a broad-spectrum-β-lactamase inhibitor combination.ceftazidime-avibactam is a broad-spectrum-β-lactamase inhibitor combination in late-stage clinical development for the treatment of serious infections. in preparation for clinical microbiology laboratory use, a validation experiment was initiated to evaluate a commercial broth microdilution product (sensititre dried mic susceptibility system) compared to reference panels using 525 recent clinical isolates. among 11 pathogen groups, all had sensititre mic/reference mic ratios predominantly at 1 ( ...201526014937
effects of different antibiotic classes on airway bacteria in stable copd using culture and molecular techniques: a randomised controlled trial.long-term antibiotic therapy is used to prevent exacerbations of copd but there is uncertainty over whether this reduces airway bacteria. the optimum antibiotic choice remains unknown. we conducted an exploratory trial in stable patients with copd comparing three antibiotic regimens against placebo.201526179246
responding to the challenge of untreatable gonorrhea: etx0914, a first-in-class agent with a distinct mechanism-of-action against bacterial type ii topoisomerases.with the diminishing effectiveness of current antibacterial therapies, it is critically important to discover agents that operate by a mechanism that circumvents existing resistance. etx0914, the first of a new class of antibacterial agent targeted for the treatment of gonorrhea, operates by a novel mode-of-inhibition against bacterial type ii topoisomerases. incorporating an oxazolidinone on the scaffold mitigated toxicological issues often seen with topoisomerase inhibitors. organisms resistan ...201526168713
the lung microbiome: new principles for respiratory bacteriology in health and disease. 201526158874
optimization of molecular approaches to genogroup neisseria meningitidis carriage isolates and implications for monitoring the impact of new serogroup b vaccines.the reservoir for neisseria meningitidis (nm) is the human oropharynx. implementation of nm serogroup c (nmc) glycoconjugate vaccines directly reduced nmc carriage. prophylactic vaccines are now available to prevent disease caused by the five major nm disease causing serogroups (abcwy). nm serogroup b (nmb) vaccines are composed of antigens that are conserved across nm serogroups and therefore have the potential to impact all nm carriage. to assess the effect of these vaccines on carriage, stand ...201526147212
sputum bacterial and fungal dynamics during exacerbations of severe copd.the changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (copd) in hospitalized patients remain largely uncharacterized. therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of copd (aecopd) would still be necessary. in our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in aecopd patie ...201526147303
the etiology and pathogenesis of chronic rhinosinusitis: a review of current hypotheses.chronic rhinosinusitis (crs) is a broad clinical syndrome that is characterized by prolonged mucosal inflammation of the nose and paranasal sinuses, and is typically divided into two subtypes based on the presence or absence of nasal polyps. the etiology and pathogenesis of both forms remain areas of active research. over the last 15 years, a number of hypotheses have been proposed to explain all or part of the clinical crs spectrum. these hypotheses reflect the concept that crs results from a d ...201526143392
the changing face of asthma and its relation with microbes.during the past 50 years, the prevalence of asthma has increased and this has coincided with our changing relation with microorganisms. asthma is a complex disease associated with local tissue inflammation of the airway that is determined by environmental, immunological, and host genetic factors. in a subgroup of sufferers, respiratory infections are associated with the development of chronic disease and more frequent inflammatory exacerbations. recent studies suggest that these infections are p ...201525840766
assessing compliance with established pneumonia core measures at a comprehensive cancer center.healthcare organizations use pneumonia core measures (pcms) to ensure delivery of high-quality care. in this study, a multidisciplinary team was organized to optimize care and enhance compliance in a comprehensive cancer emergency center. we performed a four-phase study, three of which were interventional: intense education regarding pcm; microbiologic analysis of the pathogens responsible for the pneumonias; development and implementation of an institutional pneumonia algorithm and order set. i ...201524629128
dual transcriptomic profiling of host and microbiota during health and disease in pediatric asthma.high-throughput sequencing (hts) analysis of microbial communities from the respiratory airways has heavily relied on the 16s rrna gene. given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota ...201526125632
high ifn-γ and low slpi mark severe asthma in mice and humans.severe asthma (sa) is a challenge to control, as patients are not responsive to high doses of systemic corticosteroids (cs). in contrast, mild-moderate asthma (mma) is responsive to low doses of inhaled cs, indicating that th2 cells, which are dominant in mma, do not solely orchestrate sa development. here, we analyzed broncholalveolar lavage cells isolated from mma and sa patients and determined that ifn-γ (th1) immune responses are exacerbated in the airways of individuals with sa, with reduce ...201526121748
acute exacerbations of copd are associated with significant activation of matrix metalloproteinase 9 irrespectively of airway obstruction, emphysema and infection.acute exacerbations of chronic obstructive pulmonary disease (ae-copd) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. the mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. in this study, we investigated if ae-copd are associated with differential expression of matrix metalloproteinases (mmps) and their tissue inhibitors (timps) in bronchoalveolar lavage (bal).201526126526
perioperative microbiologic monitoring of sputum on postoperative day one as a predictor of pneumonia after hepatectomy.the purpose of this study was to retrospectively evaluate microbial examination of sputum on postoperative day one (pod1) and to determine risk factors for postoperative pneumonia (pop) after hepatectomy.201526105551
evaluation of four commercial multiplex molecular tests for the diagnosis of acute respiratory infections.acute respiratory infections (aris) are responsible for considerable morbidity and mortality worldwide. documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. here, we compared the performances of four commercial multiplex kits used in french university hospital diagnostic microbiology laboratories for the detection of ari pat ...201526107509
bacterial and respiratory viral interactions in the etiology of acute otitis media in hiv-infected and hiv-uninfected south african children.bacteria and respiratory viruses are implicated in the pathogenesis of acute otitis media (aom); however, data from low-middle income countries are sparse. we investigated the etiology of aom in hiv-infected (hiv+), hiv-uninfected (hiv-) and hiv-exposed clinically asymptomatic for hiv-infection (heu) south african children.201525923426
expression of the oligopeptide permease operon of moraxella catarrhalis is regulated by temperature and nutrient availability.moraxella catarrhalis causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. together, these two conditions contribute to enormous morbidity and mortality worldwide. the oligopeptide permease (opp) abc transport system is a nutritional virulence factor important for the utilization of peptides. the substrate binding protein oppa, which binds peptides for uptake, is a potential vaccine antigen, but little was known about the regulation of gene expres ...201526099587
trends in antibiotic resistance of streptococcus pneumoniae and haemophilus influenzae isolated from nasopharyngeal flora in children with acute otitis media in france before and after 13 valent pneumococcal conjugate vaccine introduction.after the implementation of pneumococcal conjugate vaccines (pcvs), the marked shift in streptococcus pneumoniae (pnc) serotype distribution led to a modification in pneumococcal antibiotic susceptibility. in 2011, the pattern of antibiotic prescription in france for acute otitis media in infants was greatly modified, with decreased use of third-generation cephalosporins and amoxicillin-clavulanate replaced by amoxicillin alone. to assess antibiotic strategies, here we measured the antibiotic su ...201526093673
total synthesis and structural revision of antibiotic cj-16,264.the total synthesis and structural revision of antibiotic cj-16,264 is described. starting with citronellal, the quest for the target molecule featured a novel bis-transannular diels-alder reaction that casted stereoselectively the decalin system and included the synthesis of six isomers before demystification of its true structure.201526096055
point-of-care multiplex pcr promises short turnaround times for microbial testing in hospital-acquired pneumonia--an observational pilot study in critical ill patients.the early beginning of an adequate antibiotic therapy is crucial in hospital-acquired pneumonia (hap), but depends on the results of conventional microbiological diagnostics (cmd). it was the aim of this study to evaluate the performance and turnaround times of a new point-of-care multiplex polymerase chain reaction (mpcr) system for rapid identification of pathogens and antibiotic resistance markers. we assessed the applicability of the system under real-life conditions in critical ill patients ...201526071191
high pulmonary levels of il-6 and il-1β in children with chronic suppurative lung disease are associated with low systemic ifn-γ production in response to non-typeable haemophilus influenzae.non-typeable haemophilus influenzae (nthi) is commonly associated with chronic suppurative lung disease in children. we have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce ifn-γ in response to nthi compared with healthy control children. the aim of this study was to determine if deficient nthi-specific ifn-γ production is associated with heightened systemic or airway inflammation. we measured a panel of cytokines (ifn-γ, il-1β, il-6, il-8, ...201526066058
sodium houttuyfonate inhibits biofilm formation and alginate biosynthesis-associated gene expression in a clinical strain of pseudomonas aeruginosa in vitro.the increasing multidrug resistance of pseudomonas aeruginosa has become a serious public-health problem. in the present study, the inhibitory activities of sodium houttuyfonate (sh) against biofilm formation and alginate production in a clinical strain of p.aeruginosa (ah16) were investigated in vitro using crystal violet dying and standard curve methods, respectively. the cellular morphology of p. aeruginosa treated with sh was observed using a scanning electron microscope. furthermore, revers ...201526622388
airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable copd: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function.potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qpcr) in sputum from patients with copd, although how this technique relates to culture and clinical measures of disease is unclear. we used cross-sectional and longitudinal data to test the hypotheses that qpcr is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.201526089657
a fusion protein derived from moraxella catarrhalis and neisseria meningitidis aimed for immune modulation of human b cells.moraxella igd-binding protein (mid) is a well characterized trimeric autotransporter that specifically targets the igd of b cells. we fused the membrane anchor of the meningococcal autotransporter nhha with the igd-binding region of mid (aa 962-1200) to create a chimeric protein designated as nid. the aim was to use this specific targeting to provide a better vaccine candidate against meningococci, in particular serogroup b by enhancing the immunogenicity of nhha. nid was thereafter recombinantl ...201526042357
otopathogens detected in middle ear fluid obtained during tympanostomy tube insertion: contrasting purulent and non-purulent effusions.otitis media is a prominent disease among children. previous literature indicates that otitis media is a polymicrobial disease, with haemophilus influenzae, streptococcus pneumoniae, alloiococcus otitidis and moraxella catarrhalis being the most commonly associated bacterial pathogens. recent literature suggests that introduction of pneumococcal conjugate vaccines has had an effect on the etiology of otitis media. using a multiplex pcr procedure, we sought to investigate the presence of the afor ...201526039250
diagnostic accuracy of chest x-ray and ultrasonography in detection of community acquired pneumonia; a brief report.chest x-ray (cxr) is the simplest diagnostic tool of community acquired pneumonia (cap), but it has some limitation. therefore, the aim of this study is comparing the diagnostic accuracy of cxr and chest ultrasonography (cus) in detection of cap.201526495396
in vitro activity of levofloxacin against lower respiratory tract pathogens.considerable morbidity and mortality are associated with lower respiratory tract infections (lrtis) that put a considerable strain on the health budget. selection of appropriate antibiotics as empirical therapy maximizes positive patient outcomes, and that depends on regular surveillance of infective agents and their antibiograms, which vary according to the geographical areas.201526229345
an unusual case of breathlessness in a patient with chronic myeloid leukaemia: case report.a 67-year-old caucasian male presented in january, 2013, with difficulty in breathing and pyrexia. this was following a course of antibiotics for a previous chest infection that had begun at the beginning of january and had not responded to therapy. his past medical history included chronic myeloid leukaemia, basal cell carcinoma of the throat treated in 2011, glaucoma and bilateral inguinal hernia repair (performed in 1989 and 2008). he was an ex-smoker of 21 years. his current medication was d ...201526306114
interferon at the crossroads of allergy and viral infections.ifn-α/β was first described as a potent inhibitor of viral replication, but it is now appreciated that ifn signaling plays a pleiotropic role in regulating peripheral t cell functions. recently, ifn-α/β was shown to block human th2 development by suppressing the transcription factor gata3. this effect is consistent with the role for ifn-α/β in suppressing allergic inflammatory processes by blocking granulocyte activation and il-4-mediated b cell isotype switching to ige. with the consideration o ...201526026068
pidotimod: the state of art.despite the use of antibiotics and vaccines, the frequency of respiratory tract infections is still high and these infections interest a wide range of patients, from children to aged people, including in particular these extreme categories because of the deficiency of their immune system, due to immaturity in the former case and to "immunosenescence" in the latter. for that reason immunostimulant drugs are getting more important to prevent and to attenuate infections. pidotimod (3-l-pyroglutamyl ...201525999796
haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with haemophilus influenzae colonization. here we show that glucocorticosteroids have a direct influence on the behavior of h. influenzae that may account for associated difficulties with therapy. using a mouse model of infection, we show that corticosteroid treatment promotes h. influenzae persistence. transcrip ...201525995336
the autotransporter bpab contributes to the virulence of burkholderia mallei in an aerosol model of infection.burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of gram-negative bacteria. in the present study, we report the characterization of one of these autotransporters, bpab. database searches identified the bpab gene in ten b. mallei isolates and the predicted proteins were 99-100% identical. comparative seque ...201525993100
reinforcing lipid a acylation on the cell surface of acinetobacter baumannii promotes cationic antimicrobial peptide resistance and desiccation survival.acinetobacter baumannii is an emerging gram-negative pathogen found in hospitals and intensive care units. in order to persist in hospital environments, a. baumannii withstands desiccative conditions and can rapidly develop multidrug resistance to conventional antibiotics. cationic antimicrobial peptides (camps) have served as therapeutic alternatives because they target the conserved lipid a component of the gram-negative outer membrane to lyse the bacterial cell. however, many gram-negative pa ...201525991684
application of loop-mediated isothermal amplification (lamp) assay for the rapid diagnosis of pathogenic bacteria in clinical sputum specimens of acute exacerbation of copd (aecopd).the present study explores the application of lamp for rapid diagnosis of pathogenic bacteria in clinical sputum specimens of aecopd as compared with conventional sputum culturing method. 120 sputum specimens of aecopd patients, 46 sputum specimens of healthy controls, as well as 166 serum specimens as negative controls, were evaluated by lamp assay using primers of eight typical respiratory pathogens. no cross-reactivity was observed in these negative control species using lamp assay. the lower ...201526221344
evaluation of unbiased next-generation sequencing of rna (rna-seq) as a diagnostic method in influenza virus-positive respiratory samples.unbiased nontargeted metagenomic rna sequencing (umers) has the advantage to detect known as well as unknown pathogens and, thus, can significantly improve the detection of viral, bacterial, parasitic, and fungal sequences in public health settings. in particular, conventional diagnostic methods successfully identify the putative pathogenic agent in only 30% to 40% of respiratory specimens from patients with acute respiratory illness. here, we applied umers to 24 diagnostic respiratory specimens ...201525972420
a comparison of cefditoren pivoxil 8-12 mg/kg/day and cefditoren pivoxil 16-20 mg/kg/day in treatment of children with acute presumed bacterial rhinosinusitis: a prospective, randomized, investigator-blinded, parallel-group study.cefditoren pivoxil (cdt) has been used in the treatment of rhinosinusitis. however, little is known about the efficacy of this drug at low and high doses. this study was to compare the efficacy and safety of low dose (8-12 mg/kg/day) and high dose (16-20 mg/kg/day) cdt in the treatment of children with uncomplicated acute rhinosinusitis (ars).201526045911
microbiota in allergy and asthma and the emerging relationship with the gut microbiome.asthma and atopy, classically associated with hyper-activation of the t helper 2 (th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. the ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification o ...201525974301
patients with chronic obstructive pulmonary disease and chronically colonized with haemophilus influenzae during stable disease phase have increased airway inflammation.some patients with chronic obstructive pulmonary disease (copd) show increased airway inflammation and bacterial colonization during stable phase. the aim of this study was to follow copd patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.201526005341
topical treatment with fresh human milk versus emollient on atopic eczema spots in young children: a small, randomized, split body, controlled, blinded pilot study.public health nurses report on effects of fresh human milk as treatment for conjunctivitis, rhinitis and atopic eczema (ae), the latter being highly prevalent in early childhood. emollients and topical corticosteroids are first line treatment of ae. as many caregivers have steroid phobia, alternative treatment options for mild ae are of interest. the aim of this small pilot study was to assess the potential effects and risks of applying fresh human milk locally on eczema spots in children with a ...201525935520
a prescription event monitoring study on the utility of garenoxacin, a newer fluoroquinolone in india.prescription event monitoring (pem) study is conducted worldwide. the main objective of such study is to monitor the adverse events when a drug is being prescribed in "real life clinical" settings. pem studies are being looked upon as an essential observational tool of postmarketing surveillance. garenoxacin, a newer fluoroquinolone offers an excellent spectrum of antimicrobial coverage, which includes gram-positive, gram-negative, anaerobes and atypical microorganism. this broad spectrum of act ...201526097813
reversing resistance: the next generation antibacterials.irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to "preantibiotic era." the threat is serious with the "enterococcus, staphylococcous, klebsiella, acinetobacter, pseudomonas and enterobacter" organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum β-lactamases, carbapenamases and metallo-β-lactamases. facing us is a situation where soon multidrug resistance would have sp ...201526069360
vaccines for nontypeable haemophilus influenzae: the future is now.infections due to nontypeable haemophilus influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (copd). recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. infections in people with copd result in clinic and emergency room visits, hos ...201525787137
antagonism of mir-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable haemophilus influenzae (nthi) from infected lung.pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. manipulation mirna directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. here we demonstrate that mir-328 is a key element of the host response to pulmonary infection with non-t ...201525894560
isolation and characterization of a native avirulent strain of streptococcus suis serotype 2: a perspective for vaccine development.streptococcus suis, an emerging infectious pathogen, is the cause of two large-scale outbreaks of human streptococcal toxic shock syndrome in china, and has attracted much attention from the scientific community. the genetic basis of its pathogenesis remains enigmatic, and no effective prevention measures have been established. to better understand the virulence differentiation of s. suis and develop a promising vaccine, we isolated and sequenced a native avirulent s. suis strain (05has68). anim ...201525891917
fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report.neisseria cinerea has been rarely found in blood cultures. in this study, we are reporting a case of a myelodysplastic syndrome (mds) patient in whose blood neisseria cinerea was found and led a fatal consequence. this case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients.201526131259
molecular assay for detection of genetic markers associated with decreased susceptibility to cephalosporins in neisseria gonorrhoeae.the incidence of antimicrobial-resistant neisseria gonorrhoeae continues to rise in canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (naats). we developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. real-ti ...201525878350
procalcitonin and c-reactive protein cannot differentiate bacterial or viral infection in copd exacerbation requiring emergency department visits.viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (copd) exacerbations. whether serum inflammatory markers can differentiate bacterial from virus infection in patients with copd exacerbation requiring emergency department (ed) visits remains controversial.201525926728
the infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.the nasopharynx (np) is a reservoir for microbes associated with acute respiratory infections (aris). lung inflammation resulting from aris during infancy is linked to asthma development. we examined the np microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of aris. most infants were initially colonized with staphylococcus or corynebacterium before stable colonization with all ...201525865368
ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia.ceftaroline is a new parenteral cephalosporin approved by the european medicines agency (ema) and the us food and drug administration (fda) for the treatment of complicated skin and soft tissue infections (csstis) including those due to methicillin-resistant staphylococcus aureus (mrsa), and community-acquired pneumonia (cap). ceftaroline has broad-spectrum activity against gram-positive and gram-negative bacteria and exerts its bactericidal effects by binding to penicillin-binding proteins (pbp ...201525897241
specificity of the moda11, moda12 and modd1 epigenetic regulator n(6)-adenine dna methyltransferases of neisseria meningitidis.phase variation (random on/off switching) of gene expression is a common feature of host-adapted pathogenic bacteria. phase variably expressed n(6)-adenine dna methyltransferases (mod) alter global methylation patterns resulting in changes in gene expression. these systems constitute phase variable regulons called phasevarions. neisseria meningitidis phasevarions regulate genes including virulence factors and vaccine candidates, and alter phenotypes including antibiotic resistance. the target si ...201525845594
identification and therapeutic potential of a vitronectin binding region of meningococcal msf.the human pathogen neisseria meningitides (nm) attains serum resistance via a number of mechanisms, one of which involves binding to the host complement regulator protein vitronectin. we have shown previously that the meningococcal surface fibril (msf), a trimeric autotransporter, binds to the activated form of vitronectin (avn) to increase nm survival in human serum. in this study, we aimed to identify the avn-binding region of msf to assess its potential as an antigen which can elicit antibodi ...201525826209
effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials.the purpose of this study was to evaluate the clinical benefits and safety of the long-term use of macrolides in patients with non-cystic fibrosis (non-cf) bronchiectasis.201525888483
systemic cytokine signaling via il-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?we examined whether systemic cytokine signaling via interleukin (il)-17 and growth-related oncogene-α (gro-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (opd-cb). we also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with opd-cb. currently smoking opd-cb patients (n=60, corresponding to global initiative for chronic obstructive lung disease [gold] stage i-iv) underwent recurrent blood and ...201525848245
neonatal streptococcus pneumoniae infection may aggravate adulthood allergic airways disease in association with il-17a.epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. however, little is known about the mechanisms by which early-life bacterial infection increases this risk. the aim of this study was to investigate the effect of neonatal streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. a non-lethal s. pneumoniae lung infection was established by ...201525816135
identification of alloiococcus otitidis, streptococcus pneumoniae, moraxella catarrhalis and haemophilus influenzae in children with otitis media with effusion.based on many studies, otitis media with effusion (ome) is one of the major causes of childhood hearing loss, social malformation and medical costs. the pathogenesis still remains unclear, though it is known that this complication is closely related to bacterial infections. alloiococcus otitidis, haemophilus influenzae, streptococcus pneumoniae and moraxella catarrhalis are the most common bacterial pathogens isolated from middle ear effusions (mees).201525861433
patterns of structural and sequence variation within isotype lineages of the neisseria meningitidis transferrin receptor system.neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. a surface receptor comprised of transferrin-binding proteins a and b (tbpa and tbpb), is responsible for acquiring iron from host transferrin. sequence and immunological diversity divides tbpbs into two distinct lineages; isotype i and isotype ii. two representative isotype i and ii strains, b16b6 and m982, differ in their dependence on tbpb for in vitro growth on exogenous trans ...201525800619
lantibiotic resistance.the dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. one potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. it is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. given that there are very few examples ...201525787977
pyridodiazepine amines are selective therapeutic agents for helicobacter pylori by suppressing growth through inhibition of glutamate racemase but are predicted to require continuous elevated levels in plasma to achieve clinical efficacy.a pyridodiazepine amine inhibitor of helicobacter pylori glutamate racemase (muri) was characterized. the compound was selectively active against h. pylori, and growth suppression was shown to be mediated through the inhibition of muri by several methods. in killing kinetics experiments, the compound showed concentration-independent activity, with about a 2-log loss of viability in 24 h. a demonstration of efficacy in a mouse infection model was attempted but not achieved, and this was attribute ...201525645840
ceftaroline activity against bacterial pathogens frequently isolated in u.s. medical centers: results from five years of the aware surveillance program.a total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. ceftaroline inhibited all staphylococcus aureus isolates at ≤2 μg/ml and was very active against methicillin-resistant strains (mic at which 90% of the isolates tested are inhibited [mic90], 1 μg/ml; 97.6% susceptible). among streptococcus pneumoniae isolates, the highest ceftaroline mic was 0.5 μg/ml, and ceftarolin ...201525645844
cathelicidin antimicrobial protein, vitamin d, and risk of death in critically ill patients.decreased production of cathelicidin antimicrobial protein-18 (hcap18) has been proposed to be a key mechanism linking decreased 25-hydroxyvitamin d (25d) levels with adverse outcomes among critically ill patients. however, few studies in humans have directly assessed plasma hcap18 levels, and no study has evaluated the association between hcap18 levels and adverse outcomes among critically ill patients.201525887571
impact of pneumococcal conjugate vaccine on pediatric tympanostomy tube insertion in partial immunized population.to investigate the impact of seven-valent pneumococcal conjugate vaccine on tube insertions in a partial immunized pediatric population.201525839052
bacterial immune evasion through manipulation of host inhibitory immune signaling. 201525742647
amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease.acute exacerbations of chronic obstructive pulmonary disease (copd) are often treated with antibiotics. theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (mic90). a previous study showed that most hospitalized copd patients had sputum amoxicillin concentrations <lmic90 when treated with amoxicillin/clavulanic acid. those with adequate sputum ...201525767383
riems: a software pipeline for sensitive and comprehensive taxonomic classification of reads from metagenomics datasets.fuelled by the advent and subsequent development of next generation sequencing technologies, metagenomics became a powerful tool for the analysis of microbial communities both scientifically and diagnostically. the biggest challenge is the extraction of relevant information from the huge sequence datasets generated for metagenomics studies. although a plethora of tools are available, data analysis is still a bottleneck.201525886935
reported rates of diarrhea following oral penicillin therapy in pediatric clinical trials.antibiotic-associated diarrhea (aad) is a well-recognized adverse reaction to oral penicillins. this review analyzed the literature to determine the incidence of aad following amoxicillin, amoxicillin/clavulanate, and penicillin v oral therapy in pediatric clinical trials.201525964726
the extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency.mutations in dedicator of cytokinesis 8 (dock8) cause a combined immunodeficiency (cid) also classified as autosomal recessive (ar) hyper-ige syndrome (hies). recognizing patients with cid/hies is of clinical importance because of the difference in prognosis and management.201525724123
synchrony in serum antibody response to conserved proteins of streptococcus pneumoniae in young children.conserved streptococcus pneumoniae (spn) proteins are currently under investigation as vaccine candidates. we recently identified a subset of children prone to frequent acute otitis media (aom) that we refer to as stringently-defined otitis prone (sop). we investigated the synchrony of serum antibody responses against 5 spn protein vaccine antigens, phtd, lytb, pcpa, phte, and plyd1 resulting from nasopharyngeal colonization and aom in sop children (49 observations) and non-otitis prone (nop) ch ...201525692218
replication of type 5 adenovirus promotes middle ear infection by streptococcus pneumoniae in the chinchilla model of otitis media.adenoviral infection is a major risk factor for otitis media. we hypothesized that adenovirus promotes bacterial ascension into the middle ear through the disruption of normal function in the eustachian tubes due to inflammation-induced changes. an intranasal infection model of the chinchilla was used to test the ability of type 5 adenovirus to promote middle ear infection by streptococcus pneumoniae. the hyperinflammatory adenovirus mutant dl327 and the nonreplicating adenovirus mutant h5wt300δ ...201525251686
identification of viral and bacterial pathogens from hospitalized children with severe acute respiratory illness in lusaka, zambia, 2011-2012: a cross-sectional study.morbidity and mortality from respiratory infections are higher in resource-limited countries than developed countries, but limited studies have been conducted in resource-limited settings to examine pathogens from patients with acute respiratory infections. influenza surveillance has been conducted in zambia since 2008; however, only 4.3% of patients enrolled in 2011-2012 were positive for influenza. therefore, we examined non-influenza respiratory pathogens in children with severe acute respira ...201525888024
pharmacokinetics and pharmacodynamics of multiple-dose intravenous nemonoxacin in healthy chinese volunteers.this study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. the study was composed of two stages. in the open-label stage, 500 mg or 750 mg of nemonoxacin (n = 12 each) was administered at an infusion rate of 5.56 mg/min. in the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n = 16 in each cohor ...201525534726
the influence of different fever definitions on the rate of fever in neutropenia diagnosed in children with cancer.the temperature limit defining fever (tldf) is based on scarce evidence. this study aimed to determine the rate of fever in neutropenia (fn) episodes additionally diagnosed by lower versus standard tldf.201525671574
porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis.the oral bacterium porphyromonas gingivalis has special nutrient requirements due to its asaccharolytic nature subsisting on small peptides cleaved from host proteins. using proteases and other virulence factors, p. gingivalis thrives as a component of a polymicrobial community in nutritionally favorable inflammatory environments. in this regard, p. gingivalis has a number of strategies that subvert the host immune response in ways that promote its colonization and facilitate the outgrowth of th ...201525654623
higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by streptococcus pneumoniae in young children.mucosal immunity has a crucial role in controlling human respiratory tract infections. this study characterizes the naturally acquired mucosal antibody levels to three streptococcus pneumoniae (spn) protein antigens, pneumococcal histidine triad protein d (phtd), pneumococcal choline binding protein a (pcpa), and pneumolysin (ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (aom) caused by spn. both nasopharyngeal (np) immunoglobulin g (igg) ...201525648056
animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens.biological disease models can be difficult and costly to develop and use on a routine basis. particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. when infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. therefore, alternative and easy to handle models of experimental infections are still needed to test the virule ...201525699030
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