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antimicrobial activity of antisense peptide-peptide nucleic acid conjugates against non-typeable haemophilus influenzae in planktonic and biofilm forms.antisense peptide nucleic acids (pnas) are synthetic polymers that mimic dna/rna and inhibit bacterial gene expression in a sequence-specific manner.201727986898
haemophilus influenzae type b invasive disease in amish children, missouri, usa, 2014.during 5 months in 2014, three amish children in missouri, usa, were diagnosed with invasive haemophilus influenzae type b infection. two were rural neighbors infected with a genetically similar rare strain, sequence type 45. one child had recently traveled, raising the possibility of maintenance of this strain among unvaccinated carriers in amish communities.201727983486
ceftaroline activity tested against bacterial isolates causing community-acquired respiratory tract infections and skin and skin structure infections in pediatric patients from united states hospitals: 2012-2014.ceftaroline fosamil has recently received united states food and drug administration (us-fda) approval for treatment of acute bacterial skin/skin structure infections (sssi), including those caused by methicillin-resistant staphylococcus aureus (mrsa) and community-acquired bacterial pneumonia for pediatric patients ≥2 months old. we evaluated the potency and spectrum of ceftaroline and comparators when tested against community-acquired respiratory tract (carti) and sssi pathogens from pediatric ...201627977560
histopathology of vaccine-preventable diseases.the widespread use of vaccines has been one of the most important medical advances in the last century, saving trillions of dollars and millions of lives. despite local eradication of some infections, travellers returning from affected areas may cause outbreaks through reintroduction of pathogens to individuals who are unable to receive vaccines for medical reasons or who have declined vaccination for non-medical reasons. infections that would otherwise be uncommonly encountered by anatomical pa ...201727960239
community-acquired pneumonia in the asia-pacific region.community-acquired pneumonia (cap) is an important cause of mortality and morbidity worldwide. aging population, dense urbanization, and poor access to health care make the asia-pacific region vulnerable to cap. the high incidence of cap poses a significant health and economic burden in this region. common etiologic agents in other global regions including streptococcus pneumoniae, mycoplasma pneumoniae, haemophilus influenzae, chlamydophila pneumoniae, staphylococcus aureus, and respiratory vir ...201627960208
clinical features and outcomes of ipf patients hospitalized for pulmonary infection: a japanese cohort study.many patients with idiopathic pulmonary fibrosis (ipf) undergo hospitalizations due to pulmonary infections. we retrospectively investigated the characteristics of hospitalizations due to pulmonary infection in patients with ipf to elucidate causative pathogens and mortality. we reviewed patients with ipf who were admitted between january 2008 and december 2014 for pulmonary infections including pneumonia and bronchitis. the causative pathogen, the relationship between the site of pneumonia and ...201627959904
resistance of non-typeable haemophilus influenzae biofilms is independent of biofilm size.the inflammatory middle ear disease known as otitis media can become chronic or recurrent in some cases due to failure of the antibiotic treatment to clear the bacterial etiological agent. biofilms are known culprits of antibiotic-resistant infections; however, the mechanisms of resistance for non-typeable haemophilus influenzae biofilms have not been completely elucidated. in this study, we utilized in vitro static biofilm assays to characterize clinical strain biofilms and addressed the hypoth ...201727956464
immunization with protein d from non-typeable haemophilus influenzae (nthi) induced cytokine responses and bioactive antibody production.outer membrane protein d (pd) is a highly conserved and stable protein in the outer membrane of both encapsulated (typeable) and non-capsulated (non-typeable) strains of haemophilus influenzae. as an immunogen, pd is a potential candidate vaccine against non-typeable h. influenzae (nthi) strains.201627942362
concomitant administration of a fully liquid, ready-to-use dtap-ipv-hb-prp-t hexavalent vaccine with a meningococcal serogroup c conjugate vaccine in infants.dtap-ipv-hb-prp-t or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis b, poliomyelitis and invasive diseases caused by haemophilus influenzae type b (hib). the present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup c conjugate (menc) vaccine in infants. this was a phase iii, open-label, randomised, multicentre study ...201727939054
an atypical α/β-hydrolase fold revealed in the crystal structure of pimeloyl-acyl carrier protein methyl esterase biog from haemophilus influenzae.pimeloyl-acyl carrier protein (acp) methyl esterase is an α/β-hydrolase that catalyzes the last biosynthetic step of pimeloyl-acp, a key intermediate in biotin biosynthesis. intriguingly, multiple nonhomologous isofunctional forms of this enzyme that lack significant sequence identity are present in diverse bacteria. one such esterase, escherichia coli bioh, has been shown to be a typical α/β-hydrolase fold enzyme. to gain further insights into the role of this step in biotin biosynthesis, we ha ...201627933801
a novel, molybdenum-containing methionine sulfoxide reductase supports survival of haemophilus influenzae in an in vivo model of infection.haemophilus influenzae is a host adapted human mucosal pathogen involved in a variety of acute and chronic respiratory tract infections, including chronic obstructive pulmonary disease and asthma, all of which rely on its ability to efficiently establish continuing interactions with the host. here we report the characterization of a novel molybdenum enzyme, torz/mtsz that supports interactions of h. influenzae with host cells during growth in oxygen-limited environments. strains lacking torz/mts ...201627933034
fluoroquinolone consumption and -resistance trends in mycobacterium tuberculosis and other respiratory pathogens: ecological antibiotic pressure and consequences in pakistan, 2009-2015.fluoroquinolones (fqs) are important anti-tuberculous drugs for the treatment of multidrug-resistant (mdr) tuberculosis. resistance to fqs leads to fewer options for treatment of tuberculosis (tb), and infection with such strains may also require longer treatment duration. trends of resistance in mycobacterium tuberculosis (mtb) are indicators of mtb-resistance evolution. drivers of such resistance need to be understood and studied to inform preventive strategies.201627931682
invasive bacterial infections in gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.there is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (sca) in west africa, and no data from countries that have implemented conjugate vaccines against both streptococcus pneumoniae and haemophilus influenzae type b (hib).we conducted a retrospective analysis of sca patients admitted to the medical research council unit, the gambia, during a 5-year period when there was high coverage of hib and pneumococcal conjugate vaccination. we evaluated ...201627930540
expression of the gene for autotransporter autb of neisseria meningitidis affects biofilm formation and epithelial transmigration.neisseria meningitidis is a gram-negative bacterium that resides as a commensal in the upper respiratory tract of humans, but occasionally, it invades the host and causes sepsis and/or meningitis. the bacterium can produce eight autotransporters, seven of which have been studied to some detail. the remaining one, autb, has not been characterized yet. here, we show that the autb gene is broadly distributed among pathogenic neisseria spp. the gene is intact in most meningococcal strains. however, ...201627921012
bacteremic renal stone-associated urinary tract infection caused by nontypable haemophilus influenzae: a rare invasive disease in an immunocompetent patient.haemophilus species are known to colonize the upper respiratory tract and can cause infections. however haemophilus influenzae has been rarely described as a cause of genitourinary tract infection. we report a 44-year-old nonimmunocompromised japanese man with bacteremic pyelonephritis caused by a nontypable h. influenzae associated with a left ureteral calculus. the organism was isolated from both blood and urine cultures. treatment consisted of 14 days of intravenous ceftriaxone and oral amoxi ...201727920983
n-acetyl-l-cysteine and cysteamine as new strategies against mixed biofilms of nonencapsulated streptococcus pneumoniae and nontypeable haemophilus influenzae.acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. it is most frequently caused by encapsulated streptococcus pneumoniae and nontypeable haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in the carriage of nonencapsulated s. pneumoniae frequently, pneumococci and h. influenzae live together in the human nasopharynx, forming a self-produced biof ...201727919900
cephalosporin-3'-diazeniumdiolate no donor prodrug pyrro-c3d enhances azithromycin susceptibility of nontypeable haemophilus influenzae biofilms.pyrro-c3d is a cephalosporin-3-diazeniumdiolate nitric oxide (no) donor prodrug designed to selectively deliver no to bacterial infection sites. the objective of this study was to assess the activity of pyrro-c3d against nontypeable haemophilus influenzae (nthi) biofilms and examine the role of no in reducing biofilm-associated antibiotic tolerance. the activity of pyrro-c3d on in vitro nthi biofilms was assessed through cfu enumeration and confocal microscopy. no release measurements were perfo ...201727919896
etiology of acute otitis media in children less than 5 years of age: a pooled analysis of 10 similarly designed observational studies.acute otitis media (aom) is an important cause of childhood morbidity and antibiotic prescriptions. however, the relative importance of the well-known otopathogens, streptococcus pneumoniae (spn) and haemophilus influenzae (hflu), remains unclear because of a limited number of tympanocentesis-based studies that vary significantly in populations sampled, case definitions and heptavalent pneumococcal conjugate vaccine use.201727918383
neonatal bacterial meningitis in tikur anbessa specialized hospital, ethiopia: a 10-year retrospective review.bacterial meningitis is still a major public health threat in developing countries. it is an overwhelming infection with a high morbidity and mortality rate, especially in neonates. the aim of this study was to determine the prevalence and etiological agents that cause bacterial neonatal meningitis at tikur anbessa specialized hospital (tash).201627917346
solithromycin: a novel fluoroketolide for the treatment of community-acquired bacterial pneumonia.solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (cabp). when compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. solithromycin, like telithromycin, affects 50s ribosomal subunit formation and fu ...201627909995
increased nasopharyngeal density and concurrent carriage of streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis are associated with pneumonia in febrile children.we assessed nasopharyngeal (np) carriage of five pathogens in febrile children with and without acute respiratory infection (ari) of the upper (urti) or lower tract, attending health facilities in tanzania.201627907156
cost-effectiveness analysis of routine pneumococcal vaccination in the uk: a comparison of the phid-cv vaccine and the pcv-13 vaccine using a markov model.in 2010, the 13-valent pneumococcal conjugate vaccine (pcv-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (ipds), pneumonia and acute otitis media (aom) in the uk. using recent evidence on the impact of pcvs and epidemiological changes in the uk, we performed a cost-effectiveness analysis (cea) to compare the pneumococcal non-typeable haemophilus influenzae protein d conjugate vaccine (phid-cv) with pcv-13 in the ongoing national vac ...201627903558
oldenlandia diffusa extract inhibits biofilm formation by haemophilus influenzae clinical isolates.oldenlandia diffusa has been empirically used as a therapeutic adjunct for the treatment of respiratory infections. to establish the basic evidence of its clinical usefulness, antimicrobial and biofilm inhibitory activities of an o. diffusa extract were examined against clinical isolates of haemophilus influenzae, a major causative pathogen of respiratory and sensory organ infections. no significant growth inhibitory activity was observed during incubation for more than 6 h after the extract add ...201627902758
non-typeable haemophilus influenzae biofilm production and severity in lower respiratory tract infections in a tertiary hospital in mexico.non-typeable haemophilus influenzae (nthi) is a common opportunistic bacterial pathogen that primarily infects the respiratory mucosa. this study was conducted to assess clinical and microbiological data related to disease severity in patients with lower respiratory tract infections caused by nthi in a tertiary care hospital in mexico. nthi isolates were subjected to serotyping, antimicrobial susceptibility evaluationand analyses of β-lactamase production, genetic relatednessand biofilm formatio ...201627902411
relationships between mucosal antibodies, non-typeable haemophilus influenzae (nthi) infection and airway inflammation in copd.non-typeable haemophilus influenzae (nthi) is a key pathogen in copd, being associated with airway inflammation and risk of exacerbation. why some patients are susceptible to colonisation is not understood. we hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. the aim of our study (nct01701869) was to quantify the amount and specificity of antibodies against nthi in the lungs and the associated risk of infection and inflammation in health and copd. phle ...201627898728
human lung fibroblasts present bacterial antigens to autologous lung th cells.lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of cd4(+) th cells. during severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable haemophilus influenzae (nthi). given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating th cell responses to nthi. we demonstrate that fibroblasts express the cr ...201727895174
a naturally occurring single nucleotide polymorphism in a multicopy plasmid produces a reversible increase in antibiotic resistance.cole1 plasmids are small mobilizable replicons that play an important role in the spread of antibiotic resistance in pasteurellaceae in this study, we describe how a natural single nucleotide polymorphism (snp) near the origin of replication of the cole1-type plasmid pb1000 found in a pasteurella multocida clinical isolate generates two independent plasmid variants able to coexist in the same cell simultaneously. using the haemophilus influenzae rd kw20 strain as a model system, we combined anti ...201727895020
immunogenicity and safety of a liquid hexavalent vaccine in indian infants.to evaluate the immunogenicity and safety of a fully liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis b-haemophilus influenzae type b (dtap-ipv- hb-prp~t) vaccine in indian infants.201727889711
analysis of streptococcus pneumoniae and haemophilus influenzae isolated from middle ear fluid before and after the introduction of government subsidies for pneumococcal and h. influenzae type b vaccines in japan.this study aimed to identify trends in frequency, serotype, and antimicrobial susceptibility of streptococcus pneumoniae and haemophilus influenzae isolated from middle ear fluid specimens of children aged≤15 years (mean, 2 years), before and after the introduction of the 7-valent pneumococcal conjugate vaccine (pcv7) and the h. influenzae type b vaccine, at a pediatric facility in japan. sixty-six s. pneumoniae and 88 h. influenzae strains were isolated from 820 middle ear fluid samples. seroty ...201727889249
multiplex pcr reveals that viruses are more frequent than bacteria in children with cystic fibrosis.cystic fibrosis is a degenerative disease characterized by progressive epithelial secretory gland dysfunction associated with repeated respiratory infections. bacterial infections are very frequent in children with cystic fibrosis, but because rapid methods: for screening for the wide variety of potentially involved viruses were unavailable until recently, the frequency of viral presence is unknown. multiplex pcr enables screening for many viruses involved in respiratory infections.201727886635
identification of chemical compounds that inhibit protein synthesis in pseudomonas aeruginosa.four inhibitory compounds were identified using a poly-uridylic acid (polyu) mrna-directed aminoacylation/translation (a/t) protein synthesis system composed of phenylalanyl-trna synthetases (phers), ribosomes, and ribosomal factors from pseudomonas aeruginosa in an in vitro screen of a synthetic compound library. the compounds were specific for inhibition of bacterial protein synthesis. in enzymatic assays, the compounds inhibited protein synthesis with ic50 values ranging from 20 to 60 μm. min ...201627872201
rise in haemophilus influenzae with reduced quinolone susceptibility and development of a simple screening method.β-lactamase-nonproducing ampicillin-resistant haemophilus influenzae are prevalent in japan. resistance has increased as a consequence of the expanded use of antimicrobial agents, raising concerns about the rise of multidrug (macrolide and fluoroquinolone)-resistant h. influenzae.201727870809
study of greek children and youths with cystic fibrosis identifies immunisation gaps and delays.data about immunisation rates in cystic fibrosis (cf) patients are scarce. we estimated the rates and timeliness of immunisations in cf patients aged 0.55-22 years.201727862309
global routine vaccination coverage, 2015.in 1974, the world health organization (who) established the expanded program on immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). based on 2015 who and united nations children's fund (unicef) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (dtp3), the first dose of measles-containing vaccine (mcv1) and the third dose of polio vaccine (pol3) has remained stable (84%-86%) since 2010. from 20 ...201627855146
evasion of neutrophil extracellular traps by respiratory pathogens.the release of neutrophil extracellular traps (nets) is a major immune mechanism intended to capture pathogens. these histone- and protease-coated dna structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. net production has been demonstrated in the lungs of m ...201727854516
the spread and clinical impact of st14cc-pbp3 type iib/a, a clonal group of non-typeable haemophilus influenzae with chromosomally mediated β-lactam resistance-a prospective observational study.increasing incidences of non-typeable haemophilus influenzae (nthi) with β-lactam resistance mediated through mutations in penicillin-binding protein 3 (blnar or rpbp3) have been observed in the past decades. recently, an rpbp3 nthi sequence type (st) 14 with pbp3 type iib/a caused a disease outbreak in a nursing home in sweden with severe outcomes, indicating increased bacterial virulence. in this prospective observational study, the epidemiology and clinical significance of the corresponding c ...201727852000
lot-to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in us infants.this multicenter phase iii study (nct01340937) evaluated the consistency of immune responses to 3 separate lots of diphtheria-tetanus toxoids-acellular pertussis 5, inactivated poliovirus vaccine, haemophilus influenzae type b, and hepatitis b (dtap5-ipv-hib-hepb), an investigational hexavalent vaccine (hv).201727846058
a phase iii randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at two, three, four and twelve months.combination vaccines simplify vaccination visits and improve coverage and timeliness. diphtheria-tetanus toxoids-acellular pertussis 5, hepatitis b, inactivated poliovirus vaccine and haemophilus influenzae type b (dtap5-hb-ipv-hib) is a new investigational, fully liquid, combination vaccine containing a 5-antigen pertussis component and is designed to protect against 6 infectious diseases.201727846055
in replay: ciliated cultures from patients with primary ciliary dyskinesia produce nitric oxide in response to haemophilus influenzae infection and proinflammatory cytokines. 201427845649
the modified gingyo-san, a chinese herbal medicine, has direct antibacterial effects against respiratory pathogens.modified gingyo-san (mgs) is empirically used to treat various respiratory infections. mgs has been reported to have antiinflammatory and antiviral activities; however, it is not known if it has an antibacterial activity. therefore, in this study, we aimed to investigate the antimicrobial activity of mgs against respiratory pathogens.201627842538
nationwide trends in bacterial meningitis before the introduction of 13-valent pneumococcal conjugate vaccine-burkina faso, 2011-2013.following introduction of haemophilus influenzae type b vaccine in 2006 and serogroup a meningococcal conjugate vaccine in 2010, streptococcus pneumoniae (sp) became the leading cause of bacterial meningitis in burkina faso. we describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (pcv13) introduction in the pediatric routine immunization program in october 2013.201627832151
airway obstruction secondary to emphysematous epiglottitis: a case report.background despite a shift in the epidemiology of epiglottitis following the introduction of the haemophilus influenzae type b vaccine, acute infectious epiglottitis continues to be a relatively common and potentially life-threatening infection in adults. epiglottitis complicated by abscess is rare, and emphysematous abscess is even less common. early diagnosis and intervention is paramount in reducing morbidity and mortality. although case reports exist, photographic depiction of this complicat ...201627821835
staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.early-onset pneumonia (eop) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. currently, however, preemptive treatment is not recommended. the aim of this study was to identify predictive factors for eop that may justify early empirical antibiotic treatment. data for all burn patients requiring ≥4 h mechanical ventilation (mv) who were admitted between january 2001 and october 2012 were extracte ...201727815777
immunoinformatics approach in designing epitope-based vaccine against meningitis-inducing bacteria (streptococcus pneumoniae, neisseria meningitidis, and haemophilus influenzae type b).meningitis infection is one of the major threats during hajj season in mecca. meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. recently, research on epitope-based vaccines has been developed intensively. such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the anti ...201627812281
community-acquired bacterial meningitis.meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. it can be acquired spontaneously in the community - community-acquired bacterial meningitis - or in the hospital as a complication of invasive procedures or head trauma (nosocomial bacterial meningitis). despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide. streptococcus pneum ...201627808261
evidence of the presence of nucleic acids and β-glucan in the matrix of non-typeable haemophilus influenzae in vitro biofilms.non-typeable haemophilus influenzae (nthi) is a gram-negative bacterium that frequently colonizes the human nasopharynx; it is a common cause of chronic and recurrent otitis media in children and of exacerbations of chronic obstructive pulmonary disease. to date, no exopolysaccharide clearly contributing to nthi biofilms has been identified. consequently, there is some debate as to whether nthi forms biofilms during colonization and infection. the present work shows that nthi can form biofilms i ...201627805043
a novel putrescine exporter sapbcdf of escherichia coli.recent research has suggested that polyamines (putrescine, spermidine, and spermine) in the intestinal tract impact the health of animals either negatively or positively. the concentration of polyamines in the intestinal tract results from the balance of uptake and export of the intestinal bacteria. however, the mechanism of polyamine export from bacterial cells to the intestinal lumen is still unclear. in escherichia coli, pote was previously identified as a transporter responsible for putresci ...201627803167
c-reactive protein in outpatients with acute exacerbation of copd: its relationship with microbial etiology and severity.c-reactive protein (crp) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (copd) exacerbations.201627799762
microorganisms causing community-acquired acute bronchitis: the role of bacterial infection.although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness.201627788254
does upregulated host cell receptor expression provide a link between bacterial adhesion and chronic respiratory disease?expression of the platelet-activating factor receptor is upregulated in the respiratory epithelium of smokers and chronic obstructive pulmonary disease patients. we have recently determined that increased expression of pafr correlates with higher levels of adhesion to human bronchial epithelial cells by non-typable haemophilus influenzae and streptococcus pneumoniae which are major bacterial pathogens in acute exacerbations of copd. in addition, we found that a pafr antagonist decreased the adhe ...201627782846
structure of the essential haemophilus influenzae udp-diacylglucosamine pyrophosphohydrolase lpxh in lipid a biosynthesis.in most gram-negative pathogens, the hydrolysis of udp-2,3-diacylglucosamine to generate lipid x in lipid a biosynthesis is catalysed by the membrane-associated enzyme lpxh. we report the crystal structure of lpxh in complex with its product, lipid x, unveiling a unique insertion lid above the conserved architecture of calcineurin-like phosphoesterases. this structure reveals elaborate interactions surrounding lipid x and provides molecular insights into the substrate selectivity, catalysis and ...201627780190
predicting the presence of bacterial pathogens in the airways of primary care patients with acute cough.bacterial testing of all patients who present with acute cough is not feasible in primary care. furthermore, the extent to which easily obtainable clinical information predicts bacterial infection is unknown. we evaluated the diagnostic value of clinical examination and testing for c-reactive protein and procalcitonin for bacterial lower respiratory tract infection.201727777252
overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study.overwhelming post-splenectomy infection (opsi) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly streptococcus pneumoniae, but also haemophilus influenzae and neisseria meningitidis. we aimed to estimate the risk of infection in this patient group. we reviewed data collected by the victorian spleen registry in australia. on registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics ...201727776576
respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in cape town, south africa.lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. children with symptoms suggestive of pulmonary tuberculosis (ptb) may have tuberculosis, other respiratory tract infections or co-infection with mycobacterium tuberculosis and other pathogens. we aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (np) samples from children with suspected ptb.201627776489
functional antibodies to haemophilus influenzae type b, neisseria meningitidis, and streptococcus pneumoniae contained in intravenous immunoglobulin products.intravenous immunoglobulin g (ivig) replacement therapy is used to prevent invasive infections in patients with primary antibody deficiency (pad). however, few studies have functionally evaluated specific antibodies against encapsulated bacteria that cause invasive infection in patients with pad. in this study, functional antibodies against haemophilus influenzae type b (hib), streptococcus pneumoniae (pneumococci), and neisseria meningitidis (meningococci) in ivig therapy were evaluated.201727774610
safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and haemophilus influenzae type b conjugate vaccine (dtpa-ipv/hib) administered in chinese infants.we conducted 3 phase iii, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (primary vaccination study) and persistence of immune responses (booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and haemophilus influenzae type b vaccine (dtpa-ipv/hib) in chinese infants and toddlers. in the pilot study (nct00964028), 50 infants (randomized 1:1) received 3 doses of dtpa-ipv/hib at 2-3-4 (group a) or 3-4-5 months of a ...201727768515
status of new vaccine introduction - worldwide, september 2016.since the global expanded program on immunization (epi) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). historically, new vaccines only became available in low-income and middle-income countries decades after being i ...201627764083
reliability of haemophilus influenzae biofilm measurement via static method, and determinants of in vitro biofilm production.information is lacking regarding the precision of microtitre plate (mtp) assays used to measure biofilm. this study investigated the precision of an mtp assay to measure biofilm production by nontypeable haemophilus influenzae (nthi) and the effects of frozen storage and inoculation technique on biofilm production. the density of bacterial final growth was determined by absorbance after 18-20 h incubation, and biofilm production was then measured by absorbance after crystal violet staining. biof ...201627763775
low and disparate seroprotection after pentavalent childhood vaccination in the lao people's democratic republic: a cross-sectional study.in lao people's democratic republic, the high burden of vaccine-preventable diseases is thought to be mainly due to low vaccine coverage. we investigated the seroprotective response against diphtheria-tetanus-whole cell pertussis-hepatitis b-haemophilus influenzae type b (dtpw-hepb-hib) vaccine in children.201727756713
imipenem heteroresistance in nontypeable haemophilus influenzae is linked to a combination of altered pbp3, slow drug influx and direct efflux regulation.to investigate the potential roles of pbps, efflux pumps and slow drug influx for imipenem heteroresistance in nontypeable haemophilus influenzae (nthi).201727756711
an outbreak of pneumococcal meningitis among older children (≥5 years) and adults after the implementation of an infant vaccination programme with the 13-valent pneumococcal conjugate vaccine in ghana.an outbreak of pneumococcal meningitis among non-infant children and adults occurred in the brong-ahafo region of ghana between december 2015 and april 2016 despite the recent nationwide implementation of a vaccination programme for infants with the 13-valent pneumococcal conjugate vaccine (pcv13).201627756235
impact of haemophilus influenzae type b conjugate vaccines on nasopharyngeal carriage in hiv-infected children and their parents from west bengal, india.in addition to reducing haemophilus influenzae type b (hib) disease in vaccinated individuals, the hib conjugate vaccine (hibcv) has indirect effects; it reduces hib disease in unvaccinated individuals by decreasing carriage. human immunodeficiency virus (hiv)-infected children are at increased risk for hib disease and live in families where multiple members may have hiv. the aim of this study is to look at the impact of 2 doses of the hibcv on nasopharyngeal carriage of hib in hiv-infected indi ...201627753766
mcrapd unlike maldi-tof ms is a suitable candidate for routine discrimination of new haemophilus influenzae strain acquisition in chronic obstructive pulmonary disease (copd) and cystic fibrosis.haemophilus influenzae new strain acquisition has been demonstrated to increase the relative risk of acute exacerbation fourfold in contrast to colonisation or chronic infection by the same strain in chronic obstructive pulmonary disease (copd). unfortunately, molecular typing techniques are not suitable for routine use due to cost, labour-intensity and need for special expertise. we tested two techniques potentially useful for routine typing, namely the newly available maldi-tof ms and the modi ...201627752148
detection of haemophilus influenzae type b, streptococcus agalactiae, streptococcus pneumoniae and neisseria meningitidis in csf specimens of children suspicious of meningitis in ahvaz, iran.meningitis is a life-threatening infection associated with a high mortality and morbidity worldwide. neisseria meningitidis, haemophilus influenzae, and streptococcus pneumoniae are the most prevalent infectious agents that cause bacterial meningitis (bm). the objective of this study was to determine the frequencies of these three bacteria using bacterial cultures and polymerase chain reaction (pcr). in our cross-sectional study, cerebrospinal fluid (csf) specimens were obtained from 196 patient ...201627742033
nasal carriage of common bacterial pathogens among healthy kindergarten children in chaoshan region, southern china: a cross-sectional study.nasal colonization with bacterial pathogens is associated with risk of invasive respiratory tract infections, but the related information for chinese healthy children is scarce.201627741941
antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: results from 2 long-term follow-up studies.to investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable haemophilus influenzae protein d conjugate vaccine (phid-cv), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (nct00624819 - study a) and 5 years (nct00891176 - study b) post-booster vaccination. in study a, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with ph ...201727736293
the immune system of hiv-exposed uninfected infants.infants born to human immunodeficiency virus (hiv) infected women are hiv-exposed but the majority remains uninfected [i.e., hiv-exposed uninfected (heu)]. heu infants suffer greater morbidity and mortality from infections compared to hiv-unexposed (hu) peers. the reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. this review comprehensively summarizes the current literature investigating the adaptive and innate immune system of heu infants. ...201627733852
reducing time to identification of aerobic bacteria and fastidious micro-organisms in positive blood cultures.rapid and early identification of micro-organisms in blood has a key role in the diagnosis of a febrile patient, in particular, in guiding the clinician to define the correct antibiotic therapy. this study presents a simple and very fast method with high performances for identifying bacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) after only 4 h of incubation. we used early bacterial growth on polyvitex chocolate agar plates inoculated with ...201627730643
ulcerated giant dermatofibroma following routine childhood vaccination in a young boy.the development of cutaneous neoplasms at immunization sites following vaccination is uncommon, and only few have been reported in the literature worldwide. we report an unusual case of an ulcerated giant dermatofibroma that developed as a chronic nonhealing plaque in the immunization scar of a young boy after vaccination.201727721753
protection against vaccine preventable diseases in children treated for acute lymphoblastic leukemia.the objective of this retrospective study was to assess protection against vaccine preventable diseases (vpds) in children treated for acute lymphoblastic leukemia (all).201727718310
[invasive haemophilus influenzae serotype b disease in adults]. 201627712847
vaccination coverage among children aged 19-35 months - united states, 2015.sustained high coverage with recommended vaccinations among children has kept many vaccine-preventable diseases at low levels in the united states (1). to assess coverage with vaccinations recommended for children by age 2 years in the united states (2), cdc analyzed data collected by the 2015 national immunization survey (nis) for children aged 19-35 months (born january 2012-may 2014). overall, coverage did not change during 2014-2015. coverage in 2015 was highest for ≥3 doses of poliovirus va ...201627711036
comparative genomic analysis of haemophilus haemolyticus and nontypeable haemophilus influenzae and a new testing scheme for their discrimination.haemophilus haemolyticus has been recently discovered to have the potential to cause invasive disease. it is closely related to nontypeable haemophilus influenzae (nt h. influenzae). nt h. influenzae and h. haemolyticus are often misidentified because none of the existing tests targeting the known phenotypes of h. haemolyticus are able to specifically identify h. haemolyticus through comparative genomic analysis of h. haemolyticus and nt h. influenzae, we identified genes unique to h. haemolytic ...201627707939
outer membrane protein 100 of aggregatibacter actinomycetemcomitans act as a biopharmaceutical target for photodynamic therapy: an in silico analysis.periodontitis is a polymicrobial, chronic, and degenerative disease that can lead to destruction of the teeth-supporting tissues and eventually to loss of teeth. aggregatibacter actinomycetemcomitans is predominantly associated with periodontal diseases. outer membrane protein (omp) 100 is a more important virulence factor of a. actinomycetemcomitans due to the effect of adhesion and invasion into human gingival epithelial cells. attachment of a. actinomycetemcomitans inhibition is significant i ...201627697516
identification of a role for trim29 in the control of innate immunity in the respiratory tract.the respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. here we found that the e3 ubiquitin ligase trim29 was a selective regulator of the activation of alveolar macrophages, the expression of type i interferons and the production of proinflammatory cytokines in the lungs. we found that deletion of trim29 enhanced macrophage production of type i interferons and protected mice from infection with influenza virus, while ch ...201627695001
effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of streptococcus pneumoniae and haemophilus influenzae among children in são paulo, brazil.in march 2010, brazil introduced the 10-valent pneumococcal conjugate vaccine (pcv10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. we investigated pcv10 effect on nasopharyngeal carriage with vaccine-type streptococcus pneumoniae (spn) and non-typeable haemophilus influenzae (nthi) among children in são paulo city. cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-pcv10). healthy pcv-naïve children aged 12-23months ...201627692770
differential effects of p38, mapk, pi3k or rho kinase inhibitors on bacterial phagocytosis and efferocytosis by macrophages in copd.pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (copd). defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the copd phenotype. small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (mapks), phosphatidyl-inositol-3 kinase (pi3k) and rho kinase (rock) are being investigated as novel therapeutics in copd. concerns exist, however, about off-t ...201627680884
resveratrol suppresses nthi-induced inflammation via up-regulation of the negative regulator myd88 short.upper respiratory tract inflammatory diseases such as asthma and chronic obstructive pulmonary diseases (copd) affect more than one-half billion people globally and are characterized by chronic inflammation that is often exacerbated by respiratory pathogens such as nontypeable haemophilus influenzae (nthi). the increasing numbers of antibiotic-resistant bacterial strains and the limited success of currently available pharmaceuticals used to manage the symptoms of these diseases present an urgent ...201627677845
acute otitis media with spontaneous tympanic membrane perforation.the principal aim of this review is to present the current knowledge regarding acute otitis media (aom) with spontaneous tympanic membrane perforation (stmp) and to address the question of whether aom with stmp is a disease with specific characteristics or a severe case of aom. pubmed was used to search for all studies published over the past 15 years using the key words "acute otitis media" and "othorrea" or "spontaneous tympanic membrane perforation". more than 250 articles were found, but onl ...201727677281
structural determinants for antitoxin identity and insulation of cross talk between homologous toxin-antitoxin systems.toxin-antitoxin (ta) systems are ubiquitous in bacteria and archaea, where they play a pivotal role in the establishment and maintenance of dormancy. under normal growth conditions, the antitoxin neutralizes the toxin. however, under conditions of stress, such as nutrient starvation or antibiotic treatment, cellular proteases degrade the antitoxin, and the toxin functions to arrest bacterial growth. we characterized the specificity determinants of the interactions between vapb antitoxins and vap ...201627672196
low prevalence of kingella kingae carriage in children aged 6-48 months in sydney, australia.a prospective observational study was conducted to estimate the prevalence of oropharyngeal carriage of kingella kingae in healthy australian pre-school children.201727669685
the epidemiology of meningitis among adults in a south african province with a high hiv prevalence, 2009-2012.meningitis is a major cause of mortality in southern africa. we aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a south african province with an 11% hiv prevalence, over 4 years.201627669564
a cross-sectional vaccination coverage study in preschool children attending nurseries-kindergartens: implications on economic crisis effect.vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs. this study assessed full and timely vaccination coverage of preschool children aged 2-3 y attending nurseries-kindergartens (n-k) nationwide at the socioeconomic crisis onset. geographically stratified cluster sampling was implemented considering prefectures as strata and n-k as clusters. the n-k were selected by simple random sampling from the s ...201727669156
an in vitro model of murine middle ear epithelium.otitis media (om), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. there is currently a lack of a well-characterised in vitro model of the middle ear (me) epithelium that replicates the complex cellular composition of the middle ear. here, we report the development of a novel in vitro m ...201627660200
prevalence of fusobacterium necrophorum in tonsils from patients with chronic tonsillitis.there was a high prevalence of fusobacterium necrophorum (fn) in patients with chronic tonsillitis in the age group 15-23 years. this indicates that fn might play an important role in the pathogenesis of chronic tonsillitis in this age group, which is also the age group in which chronic or recurrent tonsillitis is most common.201727659315
multiplexed instrument-free meningitis diagnosis on a polymer/paper hybrid microfluidic biochip.neisseria meningitidis (n. meningitidis), streptococcus pneumoniae (s. pneumoniae), and haemophilus influenzae type b (hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. herein, we report a polymer/paper hybrid microfluidic biochip integrated with l ...201727657849
synthesis of novel 15-membered 8a-azahomoerythromycin a acylides: consequences of structural modification at the c-3 and c-6 position on antibacterial activity.a novel series of 6-o-substituted 8a-aza-8a-homoerythromycin a 3-o-acylides has been discovered with potent activity against key respiratory pathogens, including those inducibly and constitutively resistant to erythromycin. the best compounds in this series 15na and 15nd showed activity comparable to telithromycin, especially against haemophilus influenzae and constitutively mlsb-resistant strains of streptococcus pneumoniae and streptococcus pyogenes. furthermore, 15na exhibited a number of dru ...201727657812
non-type b haemophilus influenzae invasive infections in north dakota and south dakota, 2013-2015.reports of children with non-type b haemophilus influenzae infection in the united states in recent years have been limited. here, we report the spectrum and severity of disease associated with invasive non-type b h influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. meningitis was the most common diagnosis. the majority of the patients had neurologic sequelae, and 1 patient died. the high proportions of hospitalization, intensive care utilization, a ...201627656134
novel broad-spectrum and long-acting parenteral cephalosporins having an acyl cyanamide moiety at the c-3 terminal: synthesis and structure-activity relationships.a series of novel 7β-[2-(2-aminothiazole-4-yl)-2-(z)-(alkoxyimino)acetamido]-cephalosporins having pyridinium-linked acyl cyanamide at the c-3 position were prepared and their antibacterial activities and pharmacokinetics profiles were evaluated. most of the compounds exhibited potent antibacterial activities against penicillin-resistant streptococcus pneumoniae (prsp) and β-lactamase non-producing penicillin-resistant haemophilus influenzae (blnar). introduction of a propenyl group between the ...201627639362
use of administrative records to assess pneumococcal conjugate vaccine impact on pediatric meningitis and pneumonia hospitalizations in rwanda.ongoing surveillance is critical to assessing pneumococcal conjugate vaccine (pcv) impact over time. however, robust prospective studies are difficult to implement in resource-poor settings. we evaluated retrospective use of routinely collected data to estimate pcv impact in rwanda.201627639280
applying central composite design and response surface methodology to optimize growth and biomass production of haemophilus influenzae type b.haemophilus influenzae type b (hib) is the leading cause of bacterial meningitis, otitis media, pneumonia, cellulitis, bacteremia, and septic arthritis in infants and young children. the hib capsule contains the major virulence factor, and is composed of polyribosyl ribitol phosphate (prp) that can induce immune system response. vaccines consisting of hib capsular polysaccharide (prp) conjugated to a carrier protein are effective in the prevention of the infections. however, due to costly proces ...201627630761
immunogenicity and safety of 3-dose primary vaccination with combined dtpa-hbv-ipv/hib in indian infants.multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. the hexavalent diphtheria-tetanus-acellular pertussis-hepatitis b-inactivated poliovirus/haemophilus influenzae type b (dtpa-hbv-ipv/hib; infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. in the current publication, we are presenting the immunogenicit ...201727629913
treatment of otitis media by transtympanic delivery of antibiotics.otitis media is the most common reason u.s. children receive antibiotics. the requisite 7- to 10-day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. we developed a drug delivery system that, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. a pentablock copolymer poloxamer 407-p ...201627629487
antibacterial fabh inhibitors with mode of action validated in haemophilus influenzae by in vitro resistance mutation mapping.fatty acid biosynthesis is essential to bacterial growth in gram-negative pathogens. several small molecules identified through a combination of high-throughput and fragment screening were cocrystallized with fabh (β-ketoacyl-acyl carrier protein synthase iii) from escherichia coli and streptococcus pneumoniae. structure-based drug design was used to merge several scaffolds to provide a new class of inhibitors. after optimization for gram-negative enzyme inhibitory potency, several compounds dem ...201627626097
a high throughput serum bactericidal assay for antibodies to haemophilus influenzae type b.the protective capacities of antibodies induced with haemophilus influenzae type b (hib) vaccines can be directly assessed in vitro with a hib-specific serum bactericidal assay (sba). however, the conventional sba requires several tedious steps including manual counting of bacterial colonies, and therefore, it is seldom used.201627595992
vaccines against major icu pathogens: where do we stand?multidrug resistance of bacterial pathogens has confronted physicians around the world with the threat of inefficacy of the antibiotic regime, which is particularly important for patients with sepsis. antibiotic resistance has revived search for alternative nonantibiotic strategies. among them, prophylaxis by vaccination is an appealing concept.201627583587
natural development of antibodies against streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis protein antigens during the first 13 years of life.conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. we evaluated the natural development of antibodies against streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis proteins during childhood. serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). we also analyzed serum samples from 24 adults. serum igg antibodies against eight pneumococcal proteins ...201627581439
antibody responses to immunizations in children with type i diabetes mellitus: a case-control study.type i diabetes mellitus (dm) has been associated with abnormalities of t cells. our objective was to assess whether antibody responses to t-cell-dependent and -independent antigens in children with dm are lower than those of children without dm. we performed a case-control study matching children with dm to children without dm by age and by assessing antibody levels to pneumococcal serotypes, haemophilus influenzae, and tetanus and diphtheria toxoids and reassessing antibody levels in patients ...201627581437
[epidemic meningitis in 2013 in republic of guinea: nesseria meningitidis w135 emergence].a prospective study conducted from 1 january to 31 december 2013 described a meningitis epidemic in republic of guinea. the identification of the germs was based on gram stain, latex agglutination and culture. during the study period, 480 suspected cases of meningitis were reported by 21 health districts. the average age was 18±8 years and 62.5% were men. the vaccination status was unknown in all patients. the largest attack rates were found in siguiri (3.2 per 10,000), kankan (2.6 per 10,000) a ...201627578236
incidence of respiratory disease during the first two years of life in children with hemodynamically significant congenital heart disease in italy: a retrospective study.children affected by hemodynamically significant congenital heart disease (hschd) experience severe respiratory complications that can increase the frequency of hospitalizations. the aim of the sinergy study was to describe the incidence of respiratory diseases and to collect information on active and passive immunoprophylaxis in the first 2 years of life. in this retrospective, multicenter, and epidemiologic study, children with hschd were enrolled across 11 italian sites. children born between ...201627573216
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