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sterilizing immunity elicited by neisseria meningitidis carriage shows broader protection than predicted by serum antibody cross-reactivity in ceacam1-humanized mice.neisseria meningitidis asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. carriage or disease evokes an immune response against the infecting strain. hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. in this study, we establish that transgenic mice expressing human ceacam1 support nasal colonization by a variety of ...201425368118
single-molecule long-read 16s sequencing to characterize the lung microbiome from mechanically ventilated patients with suspected pneumonia.in critically ill patients, the development of pneumonia results in significant morbidity and mortality and additional health care costs. the accurate and rapid identification of the microbial pathogens in patients with pulmonary infections might lead to targeted antimicrobial therapy with potentially fewer adverse effects and lower costs. major advances in next-generation sequencing (ngs) allow culture-independent identification of pathogens. the present study used ngs of essentially full-lengt ...201425143582
targeting pro-resolution pathways to combat chronic inflammation in copd.chronic obstructive pulmonary disease (copd) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise copd airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. excessive production of leukocyte mobilising cytokines such a ...201425478196
development of a population pharmacokinetic model characterizing the tissue distribution of azithromycin in healthy subjects.recent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. the objective of our study was to simultaneously characterize free target site concentrations and correlate them with the mic90s of clinically relevant pathogens. azithromycin (500 mg once daily [qd]) was administered orally to 6 healthy male volunteers for 3 days. the free concentrations in the interstitial space fluid (isf) of muscle and subcutaneous fat tissue as well as the ...201425155592
role of the oligopeptide permease abc transporter of moraxella catarrhalis in nutrient acquisition and persistence in the respiratory tract.moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. m. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. m. catarrhalis has a putative oligopeptide permease abc transport operon (opp) consisting of five genes (oppb, oppc, oppd, oppf, and oppa), encoding two permeases, tw ...201425156736
delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. we sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock.201425148597
limits for antibiotic treatment set too narrow. 201425412636
participation of the salmonella ompd porin in the infection of raw264.7 macrophages and balb/c mice.salmonella typhimurium is the etiological agent of gastroenteritis in humans and enteric fever in mice. inside these hosts, salmonella must overcome hostile conditions to develop a successful infection, a process in which the levels of porins may be critical. herein, the role of the salmonella typhimurium porin ompd in the infection process was assessed for adherence, invasion and proliferation in raw264.7 mouse macrophages and in balb/c mice. in cultured macrophages, a δompd strain exhibited in ...201425360745
enhanced mucosal antibody production and protection against respiratory infections following an orally administered bacterial extract.secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza. we have assessed whether administration of a bacterial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infection ...201425593914
maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media.a randomized trial of an investigational 9-valent pneumococcal conjugate vaccine (pcv-9) or placebo given to pregnant women during the last trimester to prevent early infant otitis media (om) was conducted. all infants received prevnar(®) at 2, 4, 6, and 12 months. clinic and adverse event records were reviewed to identify om. variables significantly related to acute om by age 6 months (p<0.05) were: vaccine group (9 valent or placebo), sibling history of tympanostomy tubes, upper respiratory in ...201425444821
evaluation of swabbing methods for estimating the prevalence of bacterial carriage in the upper respiratory tract: a cross sectional study.bacterial carriage in the upper respiratory tract is usually asymptomatic but can lead to respiratory tract infection (rti), meningitis and septicaemia. we aimed to provide a baseline measure of streptococcus pneumoniae, moraxella catarrhalis, pseudomonas aeruginosa, staphylococcus aureus, haemophilus influenzae and neisseria meningitidis carriage within the community. self-swabbing and healthcare professional (hcp) swabbing were compared.201425358677
cilia dysfunction in lung disease.a characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes composed of microtubules and dynein arms, which provide atp-driven motility. in the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. the prototypical disorder of respiratory cilia is primary ciliary dyskinesia, ...201425386990
cilia dysfunction in lung disease.a characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes composed of microtubules and dynein arms, which provide atp-driven motility. in the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. the prototypical disorder of respiratory cilia is primary ciliary dyskinesia, ...201425386990
human nlrp3 inflammasome senses multiple types of bacterial rnas.inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines il-1β and il-18. previous studies demonstrated that bacterial rnas activate the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (nlrp3) inflammasome in both human and murine macrophages. interestingly, only mrna, but neither trna nor rrnas, derived from bacteria could activate the murine nlrp3 inflammasome. here ...201425355909
icon: chronic rhinosinusitis.chronic rhinosinusitis (crs) is a public health problem that has a significant socio-economic impact. moreover, the complexity of this disease due to its heterogeneous nature based on the underlying pathophysiology - leading to different disease variants - further complicates our understanding and directions for the most appropriate targeted treatment strategies. several international/national guidelines/position papers and/or consensus documents are available that present the current knowledge ...201425379119
a prospective cohort study of the use of domiciliary intravenous antibiotics in bronchiectasis.we introduced domiciliary intravenous (iv) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment.201425340361
novosphingobium and its potential role in chronic obstructive pulmonary diseases: insights from microbiome studies.bacterial infection of lung airways underlies some of the main complications of copd, significantly impacting disease progression and outcome. colonization by bacteria may further synergize, amplify, or trigger pathways of tissue damage started by cigarette smoke, contributing to the characteristic airway inflammation and alveolar destruction of copd. we sought to elucidate the presence and types of lung bacterial populations in different stages of copd, aimed at revealing important insights int ...201425340840
long-term macrolide therapy in chronic obstructive pulmonary disease. 201425096664
oxidative stress and free radicals in copd--implications and relevance for treatment.oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. reactive oxygen species (ros), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. when their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and re ...201425378921
microbial communities in the upper respiratory tract of patients with asthma and chronic obstructive pulmonary disease.respiratory infections are well-known triggers of chronic respiratory diseases. recently, culture-independent tools have indicated that lower airway microbiota may contribute to pathophysiologic processes associated with asthma and chronic obstructive pulmonary disease (copd). however, the relationship between upper airway microbiota and chronic respiratory diseases remains unclear. this study was undertaken to define differences of microbiota in the oropharynx of asthma and copd patients relati ...201425329665
the genomic diversification of the whole acinetobacter genus: origins, mechanisms, and consequences.bacterial genomics has greatly expanded our understanding of microdiversification patterns within a species, but analyses at higher taxonomical levels are necessary to understand and predict the independent rise of pathogens in a genus. we have sampled, sequenced, and assessed the diversity of genomes of validly named and tentative species of the acinetobacter genus, a clade including major nosocomial pathogens and biotechnologically important species. we inferred a robust global phylogeny and d ...201425313016
lower airway colonization and inflammatory response in copd: a focus on haemophilus influenzae.bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (copd) patients is common both in stable patients and during acute exacerbations. the most frequent bacteria detected in copd patients is haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with copd and to establish persistent infection in the lower respiratory tract. the presence of bacteria in the lower respiratory tract in stable copd is t ...201425342897
diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.excessive use of empirical antibiotics is common in critically ill patients. rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (vap). however, successful validation of the usefulness of potential markers in this setting is exceptionally rare.201425298325
diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.excessive use of empirical antibiotics is common in critically ill patients. rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (vap). however, successful validation of the usefulness of potential markers in this setting is exceptionally rare.201425298325
a bad case of good's syndrome.good's syndrome is a relatively rare immunodeficiency condition that presents in the fourth or fifth decade of life and is defined by hypogammaglobulinemia in the setting of a thymoma. the humoral defect may be severe enough to cause an absence in b cells, with a consequent recurrence of sinopulmonary disease, chronic non-infectious diarrhea and opportunistic infections. the prognosis in patients with good's syndrome appears to be worse than in those with x-linked agammaglobulinemia (xla) and co ...201425287948
differential gene expression of moraxella catarrhalis upon exposure to human serum.the complement system is an important part of the innate defense against invading pathogens (blom et al., 2009; [1]). the ability to resist complement-mediated killing is considered to be an important virulence trait for the human-restricted respiratory tract pathogen moraxella catarrhalis, as most disease-associated m. catarrhalis isolates are complement-resistant (wirth et al., 2007; [2]). here we provide a detailed overview of the experimental methods that we have used to study the molecular ...201426484117
influence of bronchoscopy on the diagnosis of and outcomes from ventilator-associated pneumonia.ventilator-associated pneumonia (vap) is a common healthcare-associated infection affecting as many as 27% of mechanically ventilated patients. ventilator-associated pneumonia is an important source of morbidity and mortality in the surgical intensive care unit (sicu). the optimal diagnostic method for vap has remained controversial and the role of therapeutic bronchoscopy in the clearance of pulmonary secretions with vap, in essence source control, remains unknown. our unit utilizes bronchoscop ...201424841750
endotracheal aspirate and bronchoalveolar lavage fluid analysis: interchangeable diagnostic modalities in suspected ventilator-associated pneumonia?authoritative guidelines state that the diagnosis of ventilator-associated pneumonia (vap) can be established using either endotracheal aspirate (eta) or bronchoalveolar lavage fluid (balf) analysis, thereby suggesting that their results are considered to be in accordance. therefore, the results of eta gram staining and semiquantitative cultures were compared to the results from a paired eta-balf analysis. different thresholds for the positivity of etas were assessed. this was a prospective stud ...201425078907
pathogenesis of human diffusely adhering escherichia coli expressing afa/dr adhesins (afa/dr daec): current insights and future challenges.the pathogenicity and clinical pertinence of diffusely adhering escherichia coli expressing the afa/dr adhesins (afa/dr daec) in urinary tract infections (utis) and pregnancy complications are well established. in contrast, the implication of intestinal afa/dr daec in diarrhea is still under debate. these strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult ...201425278576
clostridium difficile hfq can replace escherichia coli hfq for most of its function.a gene for the hfq protein is present in the majority of sequenced bacterial genomes. its characteristic hexameric ring-like core structure is formed by the highly conserved n-terminal regions. in contrast, the c-terminal forms an extension, which varies in length, lacks homology, and is predicted to be unstructured. in gram-negative bacteria, hfq facilitates the pairing of srnas with their mrna target and thus affects gene expression, either positively or negatively, and modulates srna degradat ...201425147238
corticosteroids in the treatment of acute asthma.asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations are among the most common causes of presentation to the emergency department (ed) and admission to hospital particularly in children. bronchial airways inflammation is the most prominent pathological feature of asthma. inhaled corticosteroids (ics), through their anti-inflammatory effects have been the mainstay of treatment of asthma for many years. systemic and ics are also used in the treatment of ac ...201425276236
activity of aristolochia bracteolata against moraxella catarrhalis.a bioassay-guided fractionation of methanol extract of aristolochia bracteolata whole plant was carried out in order to evaluate its antimicrobial activity and to identify the active compounds in this extract. antibacterial and antifungal activities of methanol extract against gram-positive, gram-negative, and fungal strains were investigated by the agar disk diffusion method. among the strains tested, moraxella catarrhalis and sea urchin-derived bacillus sp. showed the highest sensitivity towar ...201426904734
increased of exhaled breath condensate neutrophil chemotaxis in acute exacerbation of copd.neutrophils have been involved in the pathogenesis of chronic obstructive pulmonary disease (copd). underlying mechanisms of neutrophil accumulation in the airways of stable and exacerbated copd patients are poorly understood. the aim of this study was to assess exhaled breath condensate (ebc) neutrophil chemotactic activity, the level of two chemoattractants for neutrophils (gro-α and ltb4) during the course of an acute exacerbation of copd (aecopd).201425260953
clinical epidemiology and predictors of outcome in children hospitalised with influenza a(h1n1)pdm09 in 2009: a prospective national study.there are few large-scale, prospective studies of influenza a(h1n1)pdm09 in children that identify predictors of adverse outcomes.201425263176
arbekacin: another novel agent for treating infections due to methicillin-resistant staphylococcus aureus and multidrug-resistant gram-negative pathogens.arbekacin sulfate (abk), an aminoglycoside antibiotic, was discovered in 1972 and was derived from dibekacin to stabilize many common aminoglycoside modifying enzymes. abk shows broad antimicrobial activities against not only gram-positive bacteria including methicillin-resistant staphylococcus aureus (mrsa) but also gram-negative bacteria such as escherichia coli, pseudomonas aeruginosa, and klebsiella pneumoniae. abk has been approved as an injectable formulation in japan since 1990, under the ...201425298740
bacterial distribution in the lungs of children with protracted bacterial bronchitis.flexible bronchoscopy with bronchoalveolar lavage (fb-bal) is increasingly used for the microbiological confirmation of protracted bacterial bronchitis (pbb) in children with a chronic wet cough. at our centre, when performing fb-bal for microbiological diagnosis we sample 6 lobes (including lingula) as this is known to increase the rate of culture positive procedures in children with cystic fibrosis. we investigated if this is also the case in children with pbb.201425259619
clinical manifestation of macrolide antibiotic toxicity in ckd and dialysis patients.macrolide antibiotics, erythromycin, clarithromycin and azithromycin are commonly prescribed for upper respiratory infection, and their use has recently been further linked to immunomodulatory effects. with the widespread and expanded use of macrolides, special attention should be paid to their potential adverse effects. we reported two cases of end-stage renal disease (esrd) patients who developed hallucinations such as vivid images of worms after taking clarithromycin. similar to previous case ...201425859365
complete genome assembly of a quality control reference isolate, moraxella catarrhalis strain atcc 25240.generally an opportunistic pathogen in the united states, moraxella catarrhalis has acquired resistance to multiple antibacterial/antimicrobial agents. here, we present the complete 1.9-mb genome of m. catarrhalis strain atcc 25240, as deposited in ncbi under the accession number cp008804.201425237030
acute otitis media in children.acute otitis media (aom) is a common reason for primary care visits in children. yet, there is considerable debate on the most effective treatment.201425229555
systemic and pulmonary inflammation is independent of skeletal muscle changes in patients with chronic obstructive pulmonary disease.nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (copd), which has been related to systemic inflammation. it remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion.201425246784
inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease.there has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of copd patients. we investigated the relationships between the three common potentially pathogenic microorganisms (ppms) haemophilus influenzae, streptococcus pneumoniae and moraxella catarrhalis, as detected by quantitative pcr (qpcr), and inflammation and health status in stable patients in the london copd cohort.201425218165
cytokine, chemokine, and toll-like receptor expression in middle ear fluids of children with acute otitis media.acute otitis media (aom) is a common bacterial infection in childhood that causes an inflammatory response in the middle ear. leukocytes produce different inflammatory molecules in vitro when stimulated with gram-positive and gram-negative bacteria. the major causes of aom are streptococcus pneumoniae, nontypeable haemophilus influenza, and moraxella catarrhalis. we sought to assess differences in cytokines, chemokines, and expression of toll-like receptors (tlrs) at onset of aom based on bacter ...201425216361
cytokine, chemokine, and toll-like receptor expression in middle ear fluids of children with acute otitis media.acute otitis media (aom) is a common bacterial infection in childhood that causes an inflammatory response in the middle ear. leukocytes produce different inflammatory molecules in vitro when stimulated with gram-positive and gram-negative bacteria. the major causes of aom are streptococcus pneumoniae, nontypeable haemophilus influenza, and moraxella catarrhalis. we sought to assess differences in cytokines, chemokines, and expression of toll-like receptors (tlrs) at onset of aom based on bacter ...201425216361
nasal carriage and resistance pattern of multidrug resistant staphylococcus aureus among healthy children in kashan, iran.nasal carriage of staphylococcus aureus is a substantial source of human infections. detection and treatment of nasal carriage in children with methicillin-resistant and multidrug resistant s. aureus (mrsa and mdrsa, respectively) may be an important modality in prevention of infections.201425593734
exploring the origins of asthma: lessons from twin studies.this thesis explores the contribution of twin studies, particularly those studies originating from the danish twin registry, to the understanding of the aetiology of asthma. first, it is explored how twin studies have established the contribution of genetic and environmental factors to the variation in the susceptibility to asthma, and to the variation in several aspects of the clinical expression of the disease such as its age at onset, its symptomatology, its intermediate phenotypes, and its r ...201426557247
what is behind the ear drum? the microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination.this study aims to describe the microbiology of middle ear fluid (mef) in a cohort of children vaccinated with streptococcus pneumoniae conjugate vaccine (pcv7) having ventilation tube insertion. nasopharyngeal (np) carriage of otopathogens in these children is compared with children without history of otitis media.201425175818
what is behind the ear drum? the microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination.this study aims to describe the microbiology of middle ear fluid (mef) in a cohort of children vaccinated with streptococcus pneumoniae conjugate vaccine (pcv7) having ventilation tube insertion. nasopharyngeal (np) carriage of otopathogens in these children is compared with children without history of otitis media.201425175818
cardiovascular events and safety outcomes associated with azithromycin therapy: a meta-analysis of randomized controlled trials.azithromycin has been used for many years for the treatment of patients with various types of bacterial infections, as well as for the secondary prevention of coronary events. there is a growing concern, however, that azithromycin may be associated with an increased cardiovascular (cv) risk and may lead to cv-related death in high-risk patients.201425558301
three clinically distinct chronic pediatric airway infections share a common core microbiota.dna-based microbiological studies are moving beyond studying healthy human microbiota to investigate diverse infectious diseases, including chronic respiratory infections, such as those in the airways of people with cystic fibrosis (cf) and non-cf bronchiectasis. the species identified in the respiratory secretion microbiota from such patients can be classified into those that are common and abundant among similar subjects (core) versus those that are infrequent and rare (satellite). this catego ...201424597615
epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia.there are limited u.s. data describing the risk factors for multidrug-resistant organism (mdro) isolation in community-acquired pneumonia (cap) and health care-associated pneumonia (hcap). however, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for cap and hcap. a retrospective study of all adults hospitalized with community-onset pneumonia (cap and hcap) at a large u.s. medical center from january 2010 to december 2011 was conducted. the ...201424957843
chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications.chronic obstructive pulmonary disease (copd) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. the natural history of copd is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of cop ...201425177479
prevalence and risk factors for chronic co-infection in pulmonary mycobacterium avium complex disease.patients with pulmonary mycobacterium avium complex (mac) disease are often co-infected with various pathogenic microorganisms. this study aimed to determine the prevalence of co-infection with non-mac pathogens and the risk factors associated with co-infection in patients with pulmonary mac disease.201425478192
antibiotics and bacterial resistance in the 21st century.dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. in this review the factors that have been linked to this phenomenon are addressed. profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. synchronously with the waxing of b ...201425232278
the frequency of tetracycline resistance genes co-detected with respiratory pathogens: a database mining study uncovering descriptive trends throughout the united states.the center for disease control and prevention (cdc) indicates that one of the largest problems threatening healthcare includes antibiotic resistance. tetracycline, an effective antibiotic that has been in use for many years, is becoming less successful in treating certain pathogens. to better understand the temporal patterns in the growth of antibiotic resistance, patient diagnostic test records can be analyzed.201425152108
parietal subdural empyema as complication of acute odontogenic sinusitis: a case report.to date intracranial complication caused by tooth extractions are extremely rare. in particular parietal subdural empyema of odontogenic origin has not been described. a literature review is presented here to emphasize the extreme rarity of this clinical entity.201425146384
binding of human factor h to outer membrane protein p5 of non-typeable haemophilus influenzae contributes to complement resistance.non-typeable haemophilus influenzae is an opportunistic pathogen of the human upper respiratory tract and is often found to cause inflammatory diseases that include sinusitis, otitis media and exacerbations of chronic obstructive pulmonary disease. to persist in the inflammatory milieu during infection, non-typeable h. influenzae must resist the antimicrobial activity of the human complement system. here, we used tn-seq to identify genes important for resistance to complement-mediated killing. t ...201425091181
novel applications of statins for bone regeneration.the use of statins for bone regeneration is a promising and growing area of research. statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. in particular, statins can greatly affect the ...201426543666
novel applications of statins for bone regeneration.the use of statins for bone regeneration is a promising and growing area of research. statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. in particular, statins can greatly affect the ...201426543666
otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules.in 2001 when 7-valent pneumococcal conjugate vaccine (pcv7) was introduced, almost all (90%) young australian indigenous children living in remote communities had some form of otitis media (om), including 24% with tympanic membrane perforation (tmp). in late 2009, the northern territory childhood vaccination schedule replaced pcv7 with 10-valent pneumococcal haemophilus influenzae protein d conjugate vaccine (phid-cv10).201425109288
antibody-mediated immunity induced by engineered escherichia coli omvs carrying heterologous antigens in their lumen.outer membrane vesicles (omvs) from gram-negative bacteria are gaining increasing attention as vaccine platform for their built-in adjuvanticity and for their potential use as carriers of heterologous antigens. these 2 properties offer the opportunity to make highly effective, easy to produce multi-valent vaccines. omvs can be loaded with foreign antigens by targeting protein expression either to the outer membrane or to the periplasm of the omv-producing strain. periplasmic expression is simple ...201425147647
children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable haemophilus influenzae.chronic suppurative lung disease (csld) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. the aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with csld. because non-typeable haemophilus influenzae (nthi) is commonly isolated from the airways in csld, we examined immune responses to this organism in 80 age-stratified childr ...201425111142
association between pathogens detected using quantitative polymerase chain reaction with airway inflammation in copd at stable state and exacerbations.relationships between airway inflammation and respiratory potentially pathogenic microorganisms (ppms) quantified using quantitative polymerase chain reaction (qpcr) in subjects with copd are unclear. our aim was to evaluate mediators of airway inflammation and their association with ppms in subjects with copd at stable state and during exacerbations.201425103335
association between pathogens detected using quantitative polymerase chain reaction with airway inflammation in copd at stable state and exacerbations.relationships between airway inflammation and respiratory potentially pathogenic microorganisms (ppms) quantified using quantitative polymerase chain reaction (qpcr) in subjects with copd are unclear. our aim was to evaluate mediators of airway inflammation and their association with ppms in subjects with copd at stable state and during exacerbations.201425103335
contemporary concepts in management of acute otitis media in children.acute otitis media (aom) is a common disease of childhood. aom is most appropriately diagnosed by careful otoscopy with an understanding of clinical signs and symptoms. the distinction between aom and chronic otitis media with effusion should be emphasized. treatment should include pain management, and initial antibiotic treatment should be given to those most likely to benefit, including young children, children with severe symptoms, and those with otorrhea and/or bilateral aom. tympanostomy tu ...201425213276
infections in "noninfectious" lung diseases.many chronic pulmonary diseases, including those that are not primarily infectious in etiology, have some aspects of their pathogenesis that are influenced by infectious organisms. microorganisms may contribute to chronic lung diseases, either directly (i.e., overt infection) or indirectly, via the amplification of inflammatory pathways that are critical to host defense. as techniques for detecting and characterizing microorganisms have advanced, investigations of both infecting and colonizing o ...201425148428
acute bacterial sinusitis complicating viral upper respiratory tract infection in young children.acute bacterial sinusitis (abs) is a common complication of viral upper respiratory tract infections (uri). clinical characteristics of uris complicated by abs in young children have not been well studied.201424717966
development and characterization of a long-term murine model of streptococcus pneumoniae infection of the lower airways.chronic obstructive pulmonary disease (copd) is characterized by long periods of stable symptoms, but exacerbations occur, which result in a permanent worsening of symptoms. previous studies have shown a link between bacterial colonization of the lower airways of copd sufferers and an increase in exacerbation frequency. one of the most frequent bacterial colonizers is streptococcus pneumoniae. to mimic this aspect of copd, a murine model of low-level pneumococcal colonization in the lung has bee ...201424866797
characteristics of acute nongonococcal urethritis in men differ by sexual preference.nongonococcal urethritis (ngu) is a common clinical syndrome, but no etiological agent is identified in a significant proportion of cases. whether the spectrum of pathogens differs between heterosexual men (msw) and men who have sex with men (msm) is largely unstudied but of considerable clinical relevance. a retrospective review was done using the electronic medical record database of melbourne sexual health centre, australia. cases were first presentations of symptomatic acute ngu with ≥ 5 pol ...201424899041
acute mastoiditis in the pneumococcal conjugate vaccine era.following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive for streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorr ...201424920600
carriage of streptococcus pneumoniae and other respiratory bacterial pathogens in low and lower-middle income countries: a systematic review and meta-analysis.infection with streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide, especially in low income countries where pneumococcal conjugate vaccines (pcvs) are still underused. in countries where pcvs have been introduced, much of their efficacy has resulted from their impact on nasopharyngeal carriage in vaccinated children. understanding the epidemiology of carriage for s. pneumoniae and other common respiratory bacteria in developing countries is crucial for imple ...201425084351
outer membrane vesicles of pasteurella multocida contain virulence factors.pasteurella multocida (pm) is a gram-negative bacterium able to infect different animal species, including human beings. this bacterium causes economic losses to the livestock industry because of its high morbidity and mortality in animals. in this work, we report the characterization of outer membrane vesicles (omvs) released into the culture medium by different pm serogroups. purified omvs in the range of 50-300 nm were observed by electron microscopy. serum obtained from chickens infected wit ...201425065983
pulmonary manifestations of primary immunodeficiency disorders in children.primary immunodeficiencies (pids) are inherited disorders in which one or several components of immune system are decreased, missing, or of non-appropriate function. these diseases affect the development, function, or morphology of the immune system. the group of pid comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. their clinical presentation and complications depend on the type of defects and there is a g ...201425121077
development of antibiotic treatment algorithms based on local ecology and respiratory surveillance cultures to restrict the use of broad-spectrum antimicrobial drugs in the treatment of hospital-acquired pneumonia in the intensive care unit: a retrospective analysis.timely administration of appropriate antibiotic therapy has been shown to improve outcome in hospital-acquired pneumonia (hap). empirical treatment guidelines tailored to local ecology have been advocated in antibiotic stewardship programs. we compared a local ecology based algorithm (leba) to a surveillance culture based algorithm (scba) in terms of appropriate coverage and spectrum of antimicrobial activity.201425030270
maternal vaccination: moving the science forward.infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. in the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hamp ...201425015234
maternal vaccination: moving the science forward.infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. in the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hamp ...201425015234
xuan bai cheng qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial.acute exacerbation of chronic obstructive pulmonary disease (aecopd) is a common cause of morbidity and mortality. traditional chinese medicine (tcm) is used to treat aecopd as adjunctive therapy. this study aimed to evaluate the efficacy and safety of the tcm formula xuan bai cheng qi as an adjuvant therapy for aecopd patients with the syndrome type of phlegm-heat obstructing the lungs.201425014996
in vitro bactericidal and bacteriolytic activity of ceragenin csa-13 against planktonic cultures and biofilms of streptococcus pneumoniae and other pathogenic streptococci.ceragenin csa-13, a cationic steroid, is here reported to show a concentration-dependent bactericidal/bacteriolytic activity against pathogenic streptococci, including multidrug-resistant streptococcus pneumoniae. the autolysis promoted by csa-13 in pneumococcal cultures appears to be due to the triggering of the major s. pneumoniae autolysin lyta, an n-acetylmuramoyl-l-alanine amidase. csa-13 also disintegrated pneumococcal biofilms in a very efficient manner, although at concentrations slightl ...201425006964
disseminated bacillus calmette-guérin (bcg) infection following allogeneic hematopoietic stem cell transplant in a patient with bare lymphocyte syndrome type ii.we describe the first case, to our knowledge, of disseminated mycobacterium bovis bacillus calmette-guérin infection in a child with bare lymphocyte syndrome type ii after undergoing hematopoietic stem cell transplantation (hsct). the patient presented 30 days post hsct with fever and lymphadenitis. lymph node, blood, and gastric aspirates were positive for m. bovis. the patient received a prolonged treatment course with a combination of isoniazid, levofloxacin, and ethambutol. her course was fu ...201424995715
nonencapsulated streptococcus pneumoniae cause acute otitis media in the chinchilla that is enhanced by pneumococcal surface protein k.use of the pneumococcal conjugate vaccine has led to serotype replacement of carriage and acute otitis media (aom) pneumococcal isolates. increases in nonencapsulated streptococcus pneumoniae (nesp) isolates have also occurred, and there are increasing reports of nesp-associated disease. disease prevalence and virulence factors of nesp isolates have not been studied.201425734113
study of drug utilization pattern for acute exacerbation of chronic obstructive pulmonary disease in patients attending a government hospital in kerala, india.drug utilization studies are powerful exploratory tools to ascertain the role of drugs in society. this study was conducted to establish the drug utilization pattern and the common adverse drug reactions for the treatment of acute exacerbation of chronic obstructive pulmonary disease (copd) in one of the government hospitals in kerala, india.201425374864
in search of a candidate pathogen for giant cell arteritis: sequencing-based characterization of the giant cell arteritis microbiome.to characterize the microbiome of the temporal artery in patients with giant cell arteritis (gca), and to apply an unbiased and comprehensive shotgun sequencing-based approach to determine whether there is an enrichment of candidate pathogens in the affected tissue.201424644069
lps modulates rhinovirus-induced chemokine secretion in monocytes and macrophages.recent studies suggest that both bacteria and rhinoviruses (rvs) contribute to asthma exacerbations. we hypothesized that bacteria might alter antiviral responses early in the course of infection by modifying monocyte-lineage chemokine responses to rv infection. to test this hypothesis, human blood monocytes or bronchoalveolar lavage (bal) macrophages were treated with rv types a016, b014, a001, and/or a002 in the presence or absence of lps, and secretion of chemokines (cxcl10, cxcl11, ccl2, and ...201424498897
ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in europe, turkey, and israel from 2005 to 2010.ceftobiprole medocaril is a newly approved drug in europe for the treatment of hospital-acquired pneumonia (hap) (excluding patients with ventilator-associated pneumonia but including ventilated hap patients) and community-acquired pneumonia in adults. the aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent gram-positive and -negative pathogens isolated in europe, turkey, and israel during 2005 through 2010. a total of 60,084 consecutive, nondu ...201424777091
osteomyelitis of the temporal bone: terminology, diagnosis, and management.objectives to review the terminology, clinical features, and management of temporal bone osteomyelitis. design and setting prospective study in a tertiary care center from 2001 to 2008. participants twenty patients visiting the outpatient department diagnosed with osteomyelitis of the temporal bone. main outcome measures the age, sex, clinical features, cultured organisms, surgical interventions, and classification were analyzed. results of the 20 cases, 2 (10%) were diagnosed as acute otitis me ...201425302143
pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors.patients with severe chronic obstructive pulmonary disease (copd) are at increased risk of infection by p. aeruginosa. the specific role of bronchiectasis in both infection and chronic colonization by this microorganism in copd, however, remains ill defined.to evaluate the prevalence and risk factors for p. aeruginosa recovery from sputum in outpatients with severe copd, characterizing p. aeruginosa isolates by pulsed-field gel electrophoresis (pfge) and focusing on the influence of bronchiectas ...201424964956
potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. an understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct ...201424955983
microbiological profile and drug sensitivity pattern among community acquired pneumonia patients in tertiary care centre in mangalore, coastal karnataka, india.community acquired pneumonia (cap) is the most common respiratory tract infection in day to day practice. the knowledge of organism commonly causative of cap helps in early empirical treatment initiation.201425121014
haemophilus influenzae type b as an important cause of culture-positive acute otitis media in young children in thailand: a tympanocentesis-based, multi-center, cross-sectional study.streptococcus pneumoniae (s. pneumoniae) and haemophilus influenzae (h. influenzae) are considered major causes of bacterial acute otitis media (aom) worldwide, but data from asia on primary causes of aom are limited. this tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of aom in thailand.201424947736
evaluation of a real-time pcr assay for simultaneous detection of kingella kingae and staphylococcus aureus from synovial fluid in suspected septic arthritis.direct plating of synovial fluid (sf) on agar-based media often fails to identify pathogens in septic arthritis (sa). we developed a pcr assay for the simultaneous detection of kingella kingae and staphylococcus aureus from sf to evaluate molecular detection in sf and to estimate the incidence of k. kingae in sa in north america. the assay was based on detection of the cpn60 gene of k. kingae and the spa gene of s. aureus in multiplex real-time pcr. k. kingae was identified in 50% of patients be ...201424982837
comparison of scanning electron microscopy findings regarding biofilm colonization with microbiological results in nasolacrimal stents for external, endoscopic and transcanalicular dacryocystorhinostomy.to compare bacterial biofilm colonization in lacrimal stents following external dacryocystorhinostomy (ex-dcr), endoscopic dacryocystorhinostomy (en-dcr), and transcanalicular dacryocystorhinostomy (tc-dcr) with multidiode laser.201424967205
a comparative study of thin-section ct findings between seasonal influenza virus pneumonia and streptococcus pneumoniae pneumonia.to compare the pulmonary thin-section ct findings in patients with seasonal influenza virus pneumonia with streptococcus pneumoniae pneumonia.201424834476
impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.colonization of the nasopharynx by streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. the nasopharynx is also host to other bacterial species, including the common pathogens staphylococcus aureus, haemophilus influenzae, and moraxella catarrhalis. to better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative pcr to examine bacterial densities in 52 subjects 7 ...201424915552
differential response of gel-forming mucins to pathogenic middle ear bacteria.to assess the differential response of the secretory gel forming mucins (gfm) to the most common bacterial pathogens causing otitis media, streptococcus pneumoniae (sp), nontypeable haemophilus influenza (nthi), and moraxella catarrhalis (mcat), in a culture model of human middle ear epithelium (hmeec).201424958163
efficacy of pneumococcal nontypable haemophilus influenzae protein d conjugate vaccine (phid-cv) in young latin american children: a double-blind randomized controlled trial.the relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (cap) and acute otitis media (aom) is unclear. this study assessed the impact of the ten-valent pneumococcal nontypable haemophilus influenzae protein d conjugate vaccine (phid-cv) on these end points. the primary objective was to demonstrate vaccine efficacy (ve) in a per-protocol analysis against likely bacterial cap (b-cap: radiologically confirmed cap with al ...201424892763
aetiological agents of ear discharge: a two year review in a teaching hospital in ghana.the discharging ear is a common presentation in medical practice affecting all age groups but primarily children. this study shows the current aetiological causes of ear discharge and their antibiograms, data which would guide empirical treatment of ear infections, and also form a basis for further research.201425667556
selective serotonin reuptake inhibitor and bleeding in a cynomolgus macaque (macaca fascicularis).selective serotonin reuptake inhibitors (ssri) are associated with an increased bleeding risk in humans. this report describes a bleeding event in a cynomolgus macaque (macaca fascicularis) treated with the ssri sertraline hcl (zoloft). during the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. to our knowledge, this report is the first description of an ssri-related adverse event in a ...201424956214
multiplex real-time pcr assay for rapid detection of methicillin-resistant staphylococci directly from positive blood cultures.methicillin-resistant staphylococcus aureus (mrsa) is the most prevalent cause of bloodstream infections (bsis) and is recognized as a major nosocomial pathogen. this study aimed to evaluate a newly designed multiplex real-time pcr assay capable of the simultaneous detection of meca, s. aureus, and coagulase-negative staphylococci (cons) in blood culture specimens. the real-mrsa and real-mrcons multiplex real-time pcr assays (m&d, republic of korea) use the taqman probes 16s rrna for staphylococ ...201424648566
a fine-tuned interaction between trimeric autotransporter haemophilus surface fibrils and vitronectin leads to serum resistance and adherence to respiratory epithelial cells.haemophilus influenzae type b (hib) escapes the host immune system by recruitment of the complement regulator vitronectin, which inhibits the formation of the membrane attack complex (mac) by inhibiting c5b-c7 complex formation and c9 polymerization. we reported previously that hib acquires vitronectin at the surface by using haemophilus surface fibrils (hsf). here we studied in detail the interaction between hsf and vitronectin and its role in the inhibition of mac formation and the invasion of ...201424664511
identification of an outer membrane lipoprotein involved in nasopharyngeal colonization by moraxella catarrhalis in an animal model.colonization of the human nasopharynx by moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. dna microarray analysis was used to determine whether attachment of m. catarrhalis to human bronchial epithelial (hbe) cells in vitro affected gene expression in this bacterium. attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. among the upregulated genes was one (orf113) previously annotated as enc ...201424643539
interleukin 17a promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media.streptococcus pneumoniae is a gram-positive and human-restricted pathogen colonizing the nasopharynx with an absence of clinical symptoms as well as a major pathogen causing otitis media (om), one of the most common childhood infections. upon bacterial infection, neutrophils are rapidly activated and recruited to the infected site, acting as the frontline defender against emerging microbial pathogens via different ways. evidence shows that interleukin 17a (il-17a), a neutrophil-inducing factor, ...201424664502
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