Publications

TitleAbstractYear
Filter
PMID
Filter
population pharmacokinetics and pharmacodynamics of sitafloxacin in patients with community-acquired respiratory tract infections.an optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (pk-pd) analysis in patients with community-acquired respiratory tract infections (rti). a population pharmacokinetic analysis of sitafloxacin was conducted using clinical data of five clinical pharmacology studies and one clinical pk-pd study in patients with rtis. the pharmacokinetic parameters in individual patients were estimated by the bayesian method to examine any correlation between ...201323529500
μhall chip for sensitive detection of bacteria.sensitive, rapid and phenotype-specific enumeration of pathogens is essential for the diagnosis of infectious disease, monitoring of food chains, and for defense against bioterrorism. microbiological culture and genotyping, techniques that sensitively and selectively detect bacteria in laboratory settings, have limited application in clinical environments due to high cost, slow response times, and the need for specially trained staff and laboratory infrastructure. to address these challenges, we ...201323495188
innate stat3-mediated induction of the antimicrobial protein reg3γ is required for host defense against mrsa pneumonia.pulmonary staphylococcus aureus (sa) infections are a public health concern and a major complication of hyper-ige syndrome, caused by mutations in stat3. in contrast to previous findings of skin infection, we observed that clearance of sa from the lung did not require t, b, or nk cells but did require stat3 activation. immunohistochemistry showed robust stat3 phosphorylation in the lung epithelium. we identified that a critical stat3 target gene in lung epithelium is reg3g (regenerating islet-de ...201323401489
diagnostic value of symptoms and laboratory data for pertussis in adolescent and adult patients.several symptoms are classically thought to be suggestive of pertussis in children, but the diagnostic value of these symptoms in adolescent and adult patients is unclear. we evaluated the accuracy of the clinical findings for the early presumptive diagnosis of pertussis in adolescent and adult patients. furthermore, we measured fractional exhaled nitric oxide (feno) with regard to whether we could distinguish eosinophilic inflammation of the airway and pertussis. feno is not expected to be asso ...201323496900
some pneumococcal serotypes are more frequently associated with relapses of acute exacerbations in copd patients.to analyze the role of the capsular type in pneumococci causing relapse and reinfection episodes of acute exacerbation in copd patients.201323536850
il-1β promotes corneal epithelial cell migration by increasing mmp-9 expression through nf-κb- and ap-1-dependent pathways.interleukin-1β (il-1β) plays a critical mediator in the pathogenesis of eye diseases. the implication of il-1β in inflammatory responses has been shown to be mediated through up-regulation of inflammatory genes, including matrix metalloproteinase-9 (mmp-9). however, the detailed mechanisms of il-1β-induced mmp-9 expression in statens seruminstitut rabbit corneal cells (sircs) are largely unclear. here, we demonstrated that in sircs, il-1β induced mmp-9 promoter activity and mrna expression assoc ...201323505448
transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro.bacterial invasion through the blood-cerebrospinal fluid barrier (bcsfb) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the cns. in this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (pmn) and monocyte transepithelial transmigration (tm) across the bcsfb after bacterial infection.201323448224
endophthalmitis.endophthalmitis means bacterial or fungal infection inside the eye involving the vitreous and/or aqueous humors. most cases are exogenous and occur after eye surgery, after penetrating ocular trauma, or as an extension of corneal infection. an increasing number of cases are occurring after intravitreal injections of anti-vascular endothelial growth factor (vegf) medications. endophthalmitis may also be endogenous, arising from bacteraemic or fungaemic seeding of the eye. the infected eye never s ...201323438028
rhinovirus-induced exacerbations of asthma and copd.over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. this review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. exacerbations due to rhinovirus, which infects relatively fe ...201324278777
discovery of wall teichoic acid inhibitors as potential anti-mrsa β-lactam combination agents.innovative strategies are needed to combat drug resistance associated with methicillin-resistant staphylococcus aureus (mrsa). here, we investigate the potential of wall teichoic acid (wta) biosynthesis inhibitors as combination agents to restore β-lactam efficacy against mrsa. performing a whole-cell pathway-based screen, we identified a series of wta inhibitors (wtais) targeting the wta transporter protein, targ. whole-genome sequencing of wtai-resistant isolates across two methicillin-resista ...201323438756
bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (best-2): study protocol for a randomized controlled trial.bronchiectasis unrelated to cystic fibrosis (cf) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. however, high-quality evidence to inform management is scarce. oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. azithromycin has a prolonged half-li ...201323421781
efficacy of a marine bacterial nuclease against biofilm forming microorganisms isolated from chronic rhinosinusitis.the persistent colonization of paranasal sinus mucosa by microbial biofilms is a major factor in the pathogenesis of chronic rhinosinusitis (crs). control of microorganisms within biofilms is hampered by the presence of viscous extracellular polymers of host or microbial origin, including nucleic acids. the aim of this study was to investigate the role of extracellular dna in biofilm formation by bacteria associated with crs.201323441151
association of rnas with bacillus subtilis hfq.the prevalence and characteristics of small regulatory rnas (srnas) have not been well characterized for bacillus subtilis, an important model system for gram-positive bacteria. however, b. subtilis was recently found to synthesize many candidate srnas during stationary phase. in the current study, we performed deep sequencing on hfq-associated rnas and found that a small subset of srnas associates with hfq, an enigmatic rna-binding protein that stabilizes srnas in gram-negatives, but whose role ...201323457461
higher serum levels of interleukin 10 occur at onset of acute otitis media caused by streptococcus pneumoniae compared to haemophilus influenzae and moraxella catarrhalis.acute otitis media (aom) involves an inflammatory response to microbes in the middle ear that facilitates clearance of otopathogens. clinically, streptococcus pneumoniae (spn) infections of the respiratory tract are characterized by greater inflammatory responses than nontypeable haemophilus influenzae (nthi) and moraxella catarrhalis (mcat). interleukin 10 (il-10) plays an important role in down-regulating the inflammatory response. we compared serum il-10 levels in children before onset, at on ...201323404508
cefditoren versus levofloxacin in patients with exacerbations of chronic bronchitis: serum inflammatory biomarkers, clinical efficacy, and microbiological eradication.the aim of this open-label, randomized, parallel-group pilot study was to evaluate the efficacy of cefditoren pivoxil and levofloxacin in terms of speed of reduction in inflammatory parameters, clinical recovery, and microbiological eradication.201323430960
neutrophil extracellular traps and bacterial biofilms in middle ear effusion of children with recurrent acute otitis media--a potential treatment target.bacteria persist within biofilms on the middle ear mucosa of children with recurrent and chronic otitis media however the mechanisms by which these develop remain to be elucidated. biopsies can be difficult to obtain from children and their small size limits analysis.201323393551
chronic obstructive pulmonary disease.the global prevalence of physiologically defined chronic obstructive pulmonary disease (copd) in adults aged >40 yr is approximately 9-10 per cent. recently, the indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. the development of copd is multifactorial and the risk factors of copd include genetic and environmental factors. pathological changes in copd are ob ...201323563369
bacteriology of symptomatic adenoids in children.children with adenoid hypertrophy have been shown to harbor pathogenic bacteria in the nasopharynx despite antibiotics. removal of the adenoid is associated with a reduction in the bacterial count.201323641372
protective mechanisms of respiratory tract streptococci against streptococcus pyogenes biofilm formation and epithelial cell infection.streptococcus pyogenes (group a streptococci [gas]) encounter many streptococcal species of the physiological microbial biome when entering the upper respiratory tract of humans, leading to the question how gas interact with these bacteria in order to establish themselves at this anatomic site and initiate infection. here we show that s. oralis and s. salivarius in direct contact assays inhibit growth of gas in a strain-specific manner and that s. salivarius, most likely via bacteriocin secretio ...201323241973
system specificity of the tpsb transporters of coexpressed two-partner secretion systems of neisseria meningitidis.the two-partner secretion (tps) systems of gram-negative bacteria consist of a large secreted exoprotein (tpsa) and a transporter protein (tpsb) located in the outer membrane. tpsa targets tpsb for transport across the membrane via its ∼30-kda tps domain located at its n terminus, and this domain is also the minimal secretory unit. neisseria meningitidis genomes encode up to five tpsas and two tpsbs. sequence alignments of tps domains suggested that these are organized into three systems, while ...201323222722
novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals.sm-295291 and sm-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae (including penicillin-resistant strains), streptococcus pyogenes, enterococcus faecalis, klebsiella pneumoniae, moraxella catarrhalis, haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and neisseria gonorrhoeae (including ciprofloxaci ...201323147735
utility of blood culture in uncomplicated pneumonia in children.it is believed to be the standard of care to obtain a blood culture in a child who is hospitalized for pneumonia. in recent years, many studies have questioned the utility of this practice in the presence of age appropriate immunization. we conducted this study to determine the current prevalence of bacteremia in children with uncomplicated pneumonia and the utility of obtaining blood cultures in these children.201323641172
airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. underlying etiologies include severe pulmonary infection and cystic fibrosis (cf); however, in a substantial number of patients with non-cf-related bronchiectasis (ncfb), no cause is found. the increasing armamentarium of therapies now available to combat disease in cf is in stark contrast to the limited tools employed in ncfb. our study aimed to eval ...201323426081
efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (avanti).acute exacerbations of chronic bronchitis (aecb), including chronic obstructive pulmonary disease (aecopd), represent a substantial patient burden. few data exist on outpatient antibiotic management for aecb/aecopd in eastern/south eastern europe, in particular on the use of moxifloxacin (avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies.201323343427
dynamics of streptococcus pneumoniae serotypes causing acute otitis media isolated from children with spontaneous middle-ear drainage over a 12-year period (1999-2010) in a region of northern spain.the aim of this study was to determine the serotype and clonal distribution of pneumococci causing acute otitis media (aom) and their relationship with recurrences and mixed infections with other microorganisms under the influence of the 7-valent pneumococcal conjugate vaccine (pcv7). to do this, all pneumococcal isolates collected from the spontaneous middle-ear drainage of children <5 years old diagnosed of aom by their pediatrician or their general practitioner from 1999 to 2010 were phenotyp ...201323349853
high prevalence of streptococcus pneumoniae in adenoids and nasopharynx in preschool children with recurrent upper respiratory tract infections in poland--distribution of serotypes and drug resistance patterns.streptococcus pneumoniae is one of the major bacterial pathogens colonizing nasopharynx, and often causes upper respiratory tract infections in children. we investigated the prevalence of s. pneumoniae in nasopharynx and adenoid core in 57 children aged 2-5 years who underwent adenoidectomy for recurrent pharyngotonsillitis, and we determined serotypes and antibiotic resistance patterns of the isolated pneumococci.201323328644
biogeography of the ecosystems of the healthy human body.characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. previous studies mainly focused on a single body habitat from a limited set of subjects. here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans.201323316946
fueling open-source drug discovery: 177 small-molecule leads against tuberculosis.with the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against mycobacterium bovis bcg with hit confirmation in m. tuberculosis h37rv were made publicly accessible. a set of 177 potent non-cytotoxic h37rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time prov ...201323307663
viral and bacterial interactions in the upper respiratory tract.respiratory infectious diseases are mainly caused by viruses or bacteria that often interact with one another. although their presence is a prerequisite for subsequent infections, viruses and bacteria may be present in the nasopharynx without causing any respiratory symptoms. the upper respiratory tract hosts a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. this community is assumed to be constantly subject to synergistic and competitive int ...201323326226
characterization of the humoral immune response during staphylococcus aureus bacteremia and global gene expression by staphylococcus aureus in human blood.attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. therefore, more knowledge of the antigens that are expressed by staphylococcus aureus in human blood and induce an immune response in patients is required. in this study we further characterize the serial levels of igg and iga antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a s. aureus bacteremia, compare peak igg levels between patients and 30 non-inf ...201323308212
macrolide use in the treatment of critically ill patients with pneumonia: incidence, correlates, timing and outcomes.macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties.201324489569
bacterial pathogens in the nasopharynx, nasal cavity, and osteomeatal complex during wellness and viral infection.viral sinusitis can precede acute bacterial sinusitis, but the influence of viral infection on bacterial colonization is unclear. the objective of this study was to evaluate the presence of streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis in the osteomeatal complex (omc), nasal cavity, and nasopharynx in adults during wellness and viral upper respiratory illness (uri).201323406599
community-acquired pneumonia: 2012 history, mythology, and science.pneumonia remains one of the major disease entities practicing physicians must manage. it is a leading cause of infection-related morbidity and mortality in all age groups, and a leading cause of death in those older than 65 years of age. despite its frequency and importance, clinical questions have remained in the therapy of community-acquired pneumonia including when to start antibiotics, when to stop them, who to treat, and what agents to use. answers to these questions have involved historic ...201323874036
innate immune function and mortality in critically ill children with influenza: a multicenter study.to prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection.201323222256
impact of respiratory viral infections on α-hemolytic streptococci and otopathogens in the nasopharynx of young children.we studied nasopharyngeal (np) colonization in a cohort of children to determine the impact of viral upper respiratory infections (uris) on nonpneumococcal α-hemolytic streptococci (ahs) and otopathogen colonization in association with acute otitis media (aom).201323241988
human rhinoviruses.human rhinoviruses (hrvs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. advances in molecular methods have enhanced our understanding of the genomic structure of hrv and have led to the characterization of three genetically distinct hrv groups, designated groups a, b, and c, within the genus enterovirus and the family picornaviridae. hrvs are traditionally associated w ...201323297263
bacterial coinfections in travelers with malaria: rationale for antibiotic therapy.malaria predisposes children in areas where malaria is endemic to concurrent bacteremia, often with severe outcomes. the importance of bacterial coinfections in patients diagnosed with malaria in nonendemic settings has, however, not been reported. a retrospective analysis of microbiology data was performed in 755 travelers diagnosed with malaria in sweden. bacterial cultures from blood and other locations were correlated to clinical outcome and antibiotic treatment. blood cultures were drawn fr ...201323052321
diagnostic usefulness of ribosomal protein l7/l12 for pneumococcal pneumonia in a mouse model.the capsular antigen detection (cad) kit is widely used in clinics to detect streptococcus pneumoniae infection from urine, because it is rapid, convenient, and effective. however, there are several disadvantages, including false-positive results in children colonized with s. pneumoniae and prolonged positive readings even after the bacteria have been cleared. rp-l7/l12 is a component of the 50s ribosome that is abundant in all bacteria and is specific for each bacterial species. we investigated ...201323100338
the target of daptomycin is absent from escherichia coli and other gram-negative pathogens.antistaphylococcal agents commonly lack activity against gram-negative bacteria like escherichia coli owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. when these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against gram negatives. here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from e. coli and other g ...201323114759
pandemic 2009 influenza a (h1n1) virus infection in cancer and hematopoietic stem cell transplant recipients; a multicenter observational study.during march 2009 a novel influenza a virus emerged in mexico. we describe the clinical picture of the pandemic influenza a (h1n1) influenza in cancer patients during the 2009 influenza season.201425469231
pandemic 2009 influenza a (h1n1) virus infection in cancer and hematopoietic stem cell transplant recipients; a multicenter observational study.during march 2009 a novel influenza a virus emerged in mexico. we describe the clinical picture of the pandemic influenza a (h1n1) influenza in cancer patients during the 2009 influenza season.201425469231
lung disease and hypertension.chronic obstructive pulmonary disease (copd) patients are at a high risk of developing cardiovascular diseases. airflow limitation is a predictor of future risks of hypertension and cardiovascular events. copd is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. an association between inflammation and sympathetic overactivity has also been reported. in this article, we review the association between chronic lung disease and the risks of hypertension, ...201426587450
lung disease and hypertension.chronic obstructive pulmonary disease (copd) patients are at a high risk of developing cardiovascular diseases. airflow limitation is a predictor of future risks of hypertension and cardiovascular events. copd is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. an association between inflammation and sympathetic overactivity has also been reported. in this article, we review the association between chronic lung disease and the risks of hypertension, ...201426587450
the host immune dynamics of pneumococcal colonization: implications for novel vaccine development.the human nasopharynx (np) microbiota is complex and diverse and streptococcus pneumoniae (pneumococcus) is a frequent member. in the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mec ...201425668673
the host immune dynamics of pneumococcal colonization: implications for novel vaccine development.the human nasopharynx (np) microbiota is complex and diverse and streptococcus pneumoniae (pneumococcus) is a frequent member. in the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mec ...201425668673
subclinical infection and dosing in primary immunodeficiencies. 201425546767
molecular characterization of fluoroquinolone resistance in nontypeable haemophilus influenzae clinical isolates.nontypeable haemophilus influenzae (nthi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. the aims of this study were to characterize the genotypes of fluoroquinolone-resistant nthi isolates and their mechanisms of resistance. among 7,267 h. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to clinical and laboratory standards institute (clsi) criteria. in addition, a nal ...201425385097
molecular characterization of fluoroquinolone resistance in nontypeable haemophilus influenzae clinical isolates.nontypeable haemophilus influenzae (nthi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. the aims of this study were to characterize the genotypes of fluoroquinolone-resistant nthi isolates and their mechanisms of resistance. among 7,267 h. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to clinical and laboratory standards institute (clsi) criteria. in addition, a nal ...201425385097
seasonal variation in penicillin use in mexico and brazil: analysis of the impact of over-the-counter restrictions.during 2010, mexico and brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. we determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. we used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (ddd/tid) from ims health from the private sector in mexico and brazil from the first quarter of 2007 to the first quarter of 2013. this database cont ...201425313222
seasonal variation in penicillin use in mexico and brazil: analysis of the impact of over-the-counter restrictions.during 2010, mexico and brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. we determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. we used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (ddd/tid) from ims health from the private sector in mexico and brazil from the first quarter of 2007 to the first quarter of 2013. this database cont ...201425313222
predictors of viral pneumonia in patients with community-acquired pneumonia.viruses are increasingly recognized as major causes of community-acquired pneumonia (cap). few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. in this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with cap.201425531901
the adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.several cohort studies have indicated associations between s. pneumoniae and other microbes in the nasopharynx. to study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (nws). those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6b or 23f. the comp ...201425671106
effect of a fever control protocol-based strategy on ventilator-associated pneumonia in severely brain-injured patients.fever is associated with a poor outcome in severely brain-injured patients, and its control is one of the therapies used in this condition. but, fever suppression may promote infection, and severely brain-injured patients are frequently exposed to infectious diseases, particularly ventilator-associated pneumonia (vap). therefore, we designed a study to explore the role of a fever control protocol in vap development during neuro-intensive care.201425498970
no direct association between asthma and the microbiome based on currently available techniques.current uses of culture-independent tools in previous studies have shown a significant relationship between microbiota and asthma. although these studies are relatively new, there is also evidence of the possibility of new therapeutic strategies for the treatment or prevention of asthma. this article retrospectively examines the possible association between microorganisms and asthma. data on all patients with different types of asthma were collected from hospital charts from the department of in ...201425501073
chemical composition and biological activity of rubus idaeus shoots--a traditional herbal remedy of eastern europe.the young shoots of rubus idaeus are traditionally used as a herbal remedy in common cold, fever and flu-like infections yet there is no research concerning this plant material. the aim of the study was to evaluate the chemical composition and biological properties of raspberry shoots from 11 cultivar varieties.201425496130
immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of acinetobacter baumannii infection.the increasing clinical importance of infections caused by multidrug resistant acinetobacter baumannii warrants the development of novel approaches for prevention and treatment. in this context, vaccination of certain patient populations may contribute to reducing the morbidity and mortality caused by this pathogen. vaccines against gram-negative bacteria based on inactivated bacterial cells are highly immunogenic and have been shown to produce protective immunity against a number of bacterial s ...201425485716
correlation of nasopharyngeal cultures prior to and at onset of acute otitis media with middle ear fluid cultures.we sought to determine if nasopharyngeal (np) cultures taken at times of healthy visits or at onset of acute otitis media (aom) could predict the otopathogen mix and antibiotic-susceptibility of middle ear isolates as determined by middle ear fluid (mef) cultures obtained by tympanocentesis.201425475135
host-to-host variation of ecological interactions in polymicrobial infections.host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. however, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. by assuming that observed variations are random and independent, these models overlook the role of diffe ...201425473880
irak-4 and myd88 deficiencies impair igm responses against t-independent bacterial antigens.irak-4 and myd88 deficiencies impair interleukin 1 receptor and toll-like receptor (tlr) signaling and lead to heightened susceptibility to invasive bacterial infections. individuals with these primary immunodeficiencies have fewer immunoglobulin m (igm)(+)igd(+)cd27(+) b cells, a population that resembles murine splenic marginal zone b cells that mount t-independent antibody responses against bacterial antigens. however, the significance of this b-cell subset in humans is poorly understood. usi ...201425320238
severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease.bronchial colonization by potentially pathogenic microorganisms (ppms) is often demonstrated in chronic obstructive pulmonary disease (copd), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. the aim of the study was to determine changes in the bronchial microbiome of copd associated with the severity of the disease. the bronchial microbiome of copd patients was analyzed by 16s rrna gene amplification and pyrosequencing in sputum samples obtained during st ...201425253795
diseases of the middle ear in childhood.middle ear diseases in childhood play an important role in daily ent practice due to their high incidence. some of these like acute otitis media or otitis media with effusion have been studied extensively within the last decades. in this article, we present a selection of important childhood middle ear diseases and discuss the actual literature concerning their treatment, management of complications and outcome. another main topic of this paper deals with the possibilities of surgical hearing re ...201425587371
diseases of the nose and paranasal sinuses in child.diseases of the pediatric nose and nasal sinuses as well as neighboring anatomical structures encompass a variety of pathologies, especially of inflammatory nature. congenital disease, such as malformations and structural deviations of the nasal septum, as well as systemic metabolic pathologies affecting the nose and sinuses, rarely require medical therapy from an otolaryngologist. the immunological function of the mucosa and genetic factors play a role in the development of disease in the pedia ...201425587370
recognition of streptococcus pneumoniae and muramyl dipeptide by nod2 results in potent induction of mmp-9, which can be controlled by lipopolysaccharide stimulation.matrix metallopeptidase 9 (mmp-9) is a protease involved in the degradation of extracellular matrix collagen. evidence suggests that mmp-9 is involved in pathogenesis during streptococcus pneumoniae infection. however, not much is known about the induction of mmp-9 and the regulatory processes involved. we show here that the gram-positive bacteria used in this study induced large amounts of mmp-9, in contrast to the gram-negative bacteria that were used. an important pathogen-associated molecula ...201425183734
analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach.the aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. the sensitivity of these bacteria to cephalosporin, a representative ...201425446386
cephalosporinases associated with outer membrane vesicles released by bacteroides spp. protect gut pathogens and commensals against β-lactam antibiotics.to identify β-lactamase genes in gut commensal bacteroides species and to assess the impact of these enzymes, when carried by outer membrane vesicles (omvs), in protecting enteric pathogens and commensals.201425433011
cephalosporinases associated with outer membrane vesicles released by bacteroides spp. protect gut pathogens and commensals against β-lactam antibiotics.to identify β-lactamase genes in gut commensal bacteroides species and to assess the impact of these enzymes, when carried by outer membrane vesicles (omvs), in protecting enteric pathogens and commensals.201425433011
analysis of the bacterial community in chronic obstructive pulmonary disease sputum samples by denaturing gradient gel electrophoresis and real-time pcr.the global initiative defines copd for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. the world health organization (who) estimates that copd will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and hiv/aids, by 2030. the aim of this study was to determine the main stru ...201425403149
qdnamod: a statistical model-based tool to reveal intercellular heterogeneity of dna modification from smrt sequencing data.in an isogenic cell population, phenotypic heterogeneity among individual cells is common and critical for survival of the population under different environment conditions. dna modification is an important epigenetic factor that can regulate phenotypic heterogeneity. the single molecule real-time (smrt) sequencing technology provides a unique platform for detecting a wide range of dna modifications, including n6-methyladenine (6-ma), n4-methylcytosine (4-mc) and 5-methylcytosine (5-mc). here we ...201425404133
otitis media in sperm-associated antigen 6 (spag6)-deficient mice.mammalian spag6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. motile cilia are also present in the epithelial cells of the middle ear and eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. cilia defects are associated ...201425393619
role of innate immunity in the pathogenesis of otitis media.otitis media (om) is a public health problem in both developed and developing countries. it is the leading cause of hearing loss and represents a significant healthcare burden. in some cases, acute om progresses to chronic suppurative om (csom), characterized by effusion and discharge, despite antimicrobial therapy. the emergence of antibiotic resistance and potential ototoxicity of antibiotics has created an urgent need to design non-conventional therapeutic strategies against om based on moder ...201425447732
from microbial gene essentiality to novel antimicrobial drug targets.bacterial respiratory tract infections, mainly caused by streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis are among the leading causes of global mortality and morbidity. increased resistance of these pathogens to existing antibiotics necessitates the search for novel targets to develop potent antimicrobials.201425373505
ophthalmic infections in children presenting to angkor hospital for children, siem reap, cambodia.ophthalmic infections cause significant morbidity in cambodian children but aetiologic data are scarce. we investigated the causes of acute eye infections in 54 children presenting to the ophthalmology clinic at angkor hospital for children, siem reap between march and october 2012.201425369774
coagulase-negative staphylococcus culture in chronic rhinosinusitis.coagulase-negative staphylococcus (cons) is commonly isolated from patients with chronic rhinosinusitis (crs). however, the role of cons in crs remains controversial. we aimed to determine the association between positive cons culture at functional endoscopic sinus surgery (fess) and crs severity.201425367456
coagulase-negative staphylococcus culture in chronic rhinosinusitis.coagulase-negative staphylococcus (cons) is commonly isolated from patients with chronic rhinosinusitis (crs). however, the role of cons in crs remains controversial. we aimed to determine the association between positive cons culture at functional endoscopic sinus surgery (fess) and crs severity.201425367456
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
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
Displaying items 4801 - 4900 of 5747