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a molecular analysis of quinolone-resistant haemophilus influenzae: validation of the mutations in quinolone resistance-determining regions.the mechanism of quinolone-resistance is considered to be amino acid mutations in the type ii topoisomerase. we validated the genetic mechanisms of quinolone resistance in haemophilus influenzae. we obtained 29 h. influenzae strains from a nationwide surveillance program in japan (including 11 quinolone-resistant strains [moxifloxacin: mflx or levofloxacin mic ≥2 μg/ml]). we analyzed the sequences of the quinolone resistance-determining regions (qrdrs) in gyra, gyrb, parc and pare. furthermore, ...201424480551
meningitis due to haemophilus influenzae type f.with the decline in the rate of infections caused by haemophilus influenzae serotype b since the widespread vaccination, non-b serotypes should be considered as potential pathogenic agents in children with invasive disease younger than 5 years old. we report the case of an immunocompetent 1-year-old boy with haemophilus influenzae type f meningitis. the agent was identified in cerebrospinal fluid and blood cultures. serotyping was performed by tests using polyclonal sera and confirmed by polymer ...201324488395
carrier priming or suppression: understanding carrier priming enhancement of anti-polysaccharide antibody response to conjugate vaccines.with the availability of newer conjugate vaccines, immunization schedules have become increasingly complex due to the potential for unpredictable immunologic interference such as 'carrier priming' and 'carrier induced epitopic suppression'. carrier priming refers to an augmented antibody response to a carbohydrate portion of a glycoconjugate vaccine in an individual previously primed with the carrier protein. this review aims to provide a critical evaluation of the available data on carrier prim ...201424492014
antimicrobial susceptibility of gram-negative organisms isolated from patients hospitalized in intensive care units in united states and european hospitals (2009-2011).treatment of infections in the intensive care unit (icu) represents a great challenge, especially those caused by gram-negative organisms. rapid introduction of appropriate antimicrobial therapy is crucial to reduce mortality; resistance rates in the icu can be elevated due to antimicrobial selection pressure. we evaluated the antimicrobial susceptibility patterns of gram-negative bacteria isolated from patients hospitalized in icus (icu patients). the isolates were consecutively collected as pa ...201424492025
changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in uruguay.in 1994, uruguay included haemophilus influenzae b (hib) conjugated vaccine in a 3 + 1 schedule. in march 2008, 7-valent pneumococcal conjugate vaccines (pcv7) was included in a 2 +1 schedule. in 2010, 13-valent pcv replaced pcv7. catch-up immunization was offered. the aim of this study was to describe the etiology of community-acquired pneumonia (cap) in children 0-14 years of age hospitalized at the hospital pediatrico-centro hospitalario pereira rossell between 2003 and 2012.201424492286
multiple mycotic aneurysms infected with haemophilus influenzae.mycotic aneurysms are a relatively uncommon phenomenon that can pose a distinct treatment dilemma for the treating surgeon. it is rare to find haemophilus influenzae as the causative organism, and it is even more rare to find multiple aneurysms in the same patient. we present the first case to our knowledge to be described in the literature of multiple mycotic aneurysms caused by h. influenzae. the treatment presented-using high-dose antibiotics and cryopreserved homografts-has worked well in th ...201424495332
combined exposure to cigarette smoke and nontypeable haemophilus influenzae drives development of a copd phenotype in mice.cigarette smoke (cs) is the major etiologic factor of chronic obstructive pulmonary disease (copd). cs-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of copd. therefore, cs may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in copd.201424495712
bacterial meningitis in malawian adults, adolescents, and children during the era of antiretroviral scale-up and haemophilus influenzae type b vaccination, 2000-2012.we documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in malawi during introduction of haemophilus influenzae type b (hib) vaccination and the rollout of antiretroviral therapy (art).201424496208
diversity of nontypeable haemophilus influenzae strains colonizing australian aboriginal and non-aboriginal children.nontypeable haemophilus influenzae (nthi) strains are responsible for respiratory-related infections which cause a significant burden of disease in australian children. we previously identified a disparity in nthi culture-defined carriage rates between aboriginal and non-aboriginal children (42% versus 11%). the aim of this study was to use molecular techniques to accurately determine the true nthi carriage rates (excluding other culture-identical haemophilus spp.) and assess whether the nthi st ...201424501028
the impact of respiratory tract infections on the nutritional state of children with cystic fibrosis.cystic fibrosis (cf) is a life-shortening, autosomal-recessive disorder characterized by intestinal malabsorption, impaired growth and lung disease. recurrent pulmonary infections in children with cf are often associated with nutritional deficiencies.201424502062
costs of vaccine delivery in the gambia before and after, pentavalent and pneumococcal conjugate vaccine introductions.the gambia introduced seven-valent pneumococcal conjugate vaccine (pcv) in august 2009 and switched to 13-valent pcv in april 2011. in april 2009 monovalent hepatitis b and combined diphtheria-tetanus-pertussis and haemophilus influenzae type b vaccines were transitioned to a combined pentavalent vaccine. the current schedule offers three doses of pcv and pentavalent, and continues to give children monovalent hepatitis b vaccine at birth. we estimated the overall costs of the gambian immunisatio ...201424503271
ceftaroline activity tested against contemporary latin american bacterial pathogens (2011).a total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 latin american medical centers located in seven nations during 2011. isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. a total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary ...201424513484
molecular insights of co-trimoxazole resistance genes in haemophilus influenzae isolated in malaysia.in the last few decades, co-trimoxazole (sxt), an antibacterial combination of trimethoprim and sulfamethoxazole, has been used for treatment of upper respiratory tract infection due to haemophilus influenzae. the usage of this antibiotic has become less important due to emergence of sxt-resistant strains worldwide. most reports associate sxt resistance to the presence of variants of dihydrofolate reductase (dhfr) dfra genes which are responsible for trimethoprim resistance; while the sulfametho ...201324522126
[haemophilus influenzae]. 201324522312
pharmacokinetic/pharmacodynamic modeling for concentration-dependent bactericidal activity of a bicyclolide, modithromycin.the aim of this study was to develop a pharmacokinetic (pk)/pharmacodynamic (pd) model of a bicyclolide, modithromycin, to explain its concentration-dependent bactericidal activity based on the drug-bacterium interaction model that we developed. we have already reported the applicability of model to the time-dependent activity of β-lactams, and we further applied the model to the concentration-dependent activity in this study. in vitro time-kill data of modithromycin, telithromycin, and clarithr ...201424523230
effects of cigarette smoke on toll-like receptor (tlr) activation of chronic obstructive pulmonary disease (copd) macrophages.chronic obstructive pulmonary disease (copd) is characterized by an abnormal innate immune response. we have investigated the changes in the innate immune response of copd alveolar macrophages exposed to both cigarette smoke and toll-like receptor (tlr) stimulation. copd and control alveolar macrophages were exposed to cigarette smoke extract (cse) followed by tlr-2, -4 and -5 ligands [pam3csk4, lipopolysaccharide (lps) and phase i flagellin (flic), respectively] or non-typeable haemophilus infl ...201424528166
a fluorescent multiplexed bead-based immunoassay (fmia) for quantitation of igg against streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis protein antigens.streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis are pathogens commonly associated with infectious diseases in childhood. this study aimed to develop a fluorescent multiplexed bead-based immunoassay (fmia) using recombinant proteins for the quantitation of serum igg antibodies against these bacteria. eight pneumococcal proteins (ply, cbpa, pspa1, pspa2, pcpa, phtd, sp1732-3 and sp2216-1), 3 proteins of h. influenzae (nthi protein d, nthi0371-1, nthi0830), and 5 protein ...201424530690
the aetiology and antibiotic management of community-acquired pneumonia in adults in europe: a literature review.the purpose of this paper was to generate up-to-date information on the aetiology of community-acquired pneumonia (cap) and its antibiotic management in adults across europe. structured searches of pubmed identified information on the aetiology of cap and its antibiotic management in individuals aged >15 years across europe. we summarise the data from 33 studies published between january 2005 and july 2012 that reported on the pathogens identified in patients with cap and antibiotic treatment in ...201424532008
diversion of the host humoral response: a novel virulence mechanism of haemophilus influenzae mediated via outer membrane vesicles.the respiratory tract pathogen haemophilus influenzae frequently causes infections in humans. in parallel with all gram-negative bacteria, h. influenzae has the capacity to release omv. the production of these nanoparticles is an intriguing and partly unexplored phenomenon in pathogenesis. here, we investigated how purified human peripheral blood b lymphocytes respond to omv derived from unencapsulated, i.e., nthi and the nonpathogenic haemophilus parainfluenzae. we found that h. influenzae omv ...201424550522
phenotypic characterization and antibiogram of csf isolates in acute bacterial meningitis.acute bacterial meningitis (abm) is a medical emergency, which warrants an early diagnosis and an aggressive therapy. despite the availability of potent newer antibiotics, the mortality rate caused by acute bacterial meningitis remains significantly high in india and in other developing countries, which ranges from 16 - 32%. there is a need of a periodic review of bacterial meningitis worldwide, since the pathogens which are responsible for the infection may vary with time, geography and the age ...201324551618
use of vaccines as probes to define disease burden.vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. by contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. the underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. vaccine probe studies can increase understanding of a vaccine's public health value. for instance, even when a ...201424553294
there is a specific response to ph by isolates of haemophilus influenzae and this has a direct influence on biofilm formation.haemophilus influenzae colonizes the nasopharynx as a commensal. strain-specific factors allow some strains to migrate to particular anatomical niches, such as the middle ear, bronchi or blood, and induce disease by surviving within the conditions present at these sites in the body. it is established that h. influenzae colonization and in some cases survival is highly dependent on their ability to form a biofilm. biofilm formation is a key trait in the development of chronic infection by certain ...201424555828
the relationship between biofilm formations and capsule in haemophilus influenzae.to evaluate the biofilm formation of non-typeable haemophilus influenzae (nthi) and h. influenzae type b (hib) clinical isolates, we conducted the following study. serotyping and polymerase chain reaction were performed to identify β-lactamase-negative ampicillin (abpc)-susceptible (blnas), β-lactamase-negative abpc-resistant (blnar), tem-1 type β-lactamase-producing abpc-resistant (blpar)-nthi, and hib. biofilm formation was investigated by microtiter biofilm assay, as well as visually observat ...201424560562
role of inter-species recombination of the ftsi gene in the dissemination of altered penicillin-binding-protein-3-mediated resistance in haemophilus influenzae and haemophilus haemolyticus.to screen the ftsi gene sequences obtained from clinical isolates of non-typeable haemophilus influenzae (nthi) and haemophilus haemolyticus for the presence of mosaic ftsi gene structures, and to evaluate the role of inter-species recombination of the ftsi gene in the formation and distribution of resistant ftsi genes.201424562614
the effect of haemophilus influenzae type b and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review.two of the most prevalent causes of severe bacterial meningitis in children, haemophilus influenzae type b (hib) and streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. our objective was to estimate the dose-specific effect of hib and pneumococcal conjugate vaccines (pcv) on childhood meningitis mortality in low-income countries for use in the lives saved tool (list).201324564188
selection against glycosylation sites in potential target proteins of the general hmwc n-glycosyltransferase in haemophilus influenzae.the hmwabc system of non-typeable haemophilus influenzae (nthi) encodes the hmwa adhesin glycoprotein, which is glycosylated by the hmwc glycosyltransferase. hmwc is a cytoplasmic n-glycosyltransferase, homologues of which are widespread in the pasteurellaceae. we developed an assay for nonbiased detection of glycoproteins in nthi based on metabolic engineering of the leloir pathway and growth in media containing radiolabelled monosaccharides. the only glycoprotein identified in nthi by this ass ...201424565833
high cost is the primary barrier reported by physicians who prescribe vaccines not included in india's universal immunization program.haemophilus influenzae type b (hib) vaccine, pneumococcal conjugate vaccine (pcv) and rotavirus (rv) vaccine are available in the private market in india, but, except for hib in eight states, are not included in india's universal immunization program (uip). pediatricians were surveyed about administering non-uip vaccines. most give these vaccines to some of their patients (73-83%, depending on vaccine), but few give them to all patients (7-18%). high cost was the most frequently cited barrier (9 ...201424567310
extensive cotransformation of natural variation into chromosomes of naturally competent haemophilus influenzae.naturally competent bacterial species actively take up environmental dna and can incorporate it into their chromosomes by homologous recombination. this can bring genetic variation from environmental dna to recipient chromosomes, often in multiple long "donor" segments. here, we report the results of genome sequencing 96 colonies of a laboratory haemophilus influenzae strain, which had been experimentally transformed by dna from a diverged clinical isolate. donor segments averaged 6.9 kb (spanni ...201424569039
immunogenicity of haemophilus influenzae type b protein conjugate vaccines in very low birth weight infants. 201324569312
live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections.in low-income countries, live measles vaccine reduces mortality from causes other than measles infection. such nonspecific effects of vaccines might also be important for the health of children in high-income settings.201424570246
the epidemiology and aetiology of infections in children admitted with clinical severe pneumonia to a university hospital in rabat, morocco.scarce and limited epidemiological, clinical and microbiological data are available regarding paediatric respiratory tract infections in the kingdom of morocco, a middle-income country in northwestern africa. the results of hospital-based surveillance aiming at describing the aetiology and epidemiology of respiratory distress among children <5 years of age are presented.201424570343
prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (acip).this report compiles and summarizes all recommendations from cdc's advisory committee on immunization practices (acip) regarding prevention and control of haemophilus influenzae type b (hib) disease in the united states. as a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians, public health officials, vaccination providers, and immunization program personnel as a resource. acip recommends routi ...201424572654
antibodies to the hmw1/hmw2 and hia adhesins of nontypeable haemophilus influenzae mediate broad-based opsonophagocytic killing of homologous and heterologous strains.the hmw1/hmw2 and hia proteins are highly immunogenic surface adhesins of nontypeable haemophilus influenzae (nthi). approximately 75% of nthi strains express hmw1/hmw2 adhesins, and most of the remaining 25% express an hia adhesin. our objective in this study was to assess the ability of antisera raised against purified hmw1/hmw2 proteins or recombinant hia proteins to mediate opsonophagocytic killing of a large panel of unrelated nthi strains. native hmw1/hmw2 proteins were purified from three ...201424574538
the informed consent in southern italy does not adequately inform parents about infant vaccination.vaccination centres in the campania region, southern italy, vaccinate children with a hexavalent vaccine that contains the mandatory vaccines diphtheria, tetanus, poliomyelitis, and viral hepatitis b. this vaccine also includes two non-mandatory vaccines, pertussis and haemophilus influenzae type b. information about these optional vaccines should be communicated to the parents, and informed consent should be obtained from parents before vaccination. we explored whether informed consent was deli ...201424580773
changes in nasopharyngeal carriage of streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis among healthy children attending a day-care centre before and after official financial support for the 7-valent pneumococcal conjugate vaccine and h. influenzae type b vaccine in japan.the 7-valent pneumococcal conjugate vaccine (pcv7) and haemophilus influenzae type b (hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. to investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the pcv7 and hib vaccines in healthy children attending a day care centre in japan during 2011-2012 ...201424582389
ceftaroline activity against organisms isolated from respiratory tract infections in usa hospitals: results from the aware program, 2009-2011.the assessing worldwide antimicrobial resistance evaluation program monitors the activity of ceftaroline and comparator agents tested against pathogens causing either respiratory or skin and soft tissue infections. a total of 7733 isolates from patients in 80 medical centers across the united states (usa) identified as respiratory tract pathogens by the infection type and/or specimen site recorded by the submitting laboratory during 2009-2011 were evaluated. there were 3360 isolates of streptoco ...201424582578
the haemophilus cryptic genospecies cha adhesin has at least two variants that differ in host cell binding, bacterial aggregation, and biofilm formation properties.the haemophilus cryptic genospecies (hcg) causes genital tract infections in pregnant and postpartum women and respiratory infections in neonates. the major surface adhesin in hcg is called cha, which mediates bacterial adherence to cultured human epithelial cells. in this study, we report that there are two antigenically distinct variants of cha, dubbed cha1 and cha2. these variants are encoded by the same genetic locus in diverse strains and have nearly identical n-terminal export and c-termin ...201424584499
selection for phase variation of los biosynthetic genes frequently occurs in progression of non-typeable haemophilus influenzae infection from the nasopharynx to the middle ear of human patients.surface structures in haemophilus influenzae are subject to rapid on/off switching of expression, a process termed phase variation. we analyse tetranucleotide repeats controlling phase variation in lipo-oligosaccharide (los) genes of h. influenzae in paired isolates from both the nasopharynx and middle ears of paediatric patients with chronic or recurrent otitis media. a change in expression of at least one of the seven phase variable los biosynthesis genes was seen in 12 of the 21 strain pairs. ...201424587383
production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (dpt), haemophilus influenzae type b (hib), and 7-valent pneumococcal (pcv7) vaccines.haemophilus influenzae type b (hib) and 7-valent pneumococcal (pcv7) vaccines both became recommended in japan in 2010. in this study, cytokine production was investigated in peripheral blood mononuclear cells (pbmcs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (dpt), hib, and pcv7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. higher il-1β levels wer ...201324589970
ciliated cultures from patients with primary ciliary dyskinesia produce nitric oxide in response to haemophilus influenzae infection and proinflammatory cytokines. 201424590042
economic evaluation of the routine childhood immunization program in the united states, 2009.to evaluate the economic impact of the 2009 routine us childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis b, varicella, 7-valent pneumococcal conjugate, hepatitis a, and rotavirus vaccines; influenza vaccine was not included.201424590750
antimicrobial resistance trends among community-acquired respiratory tract pathogens in greece, 2009-2012.the aim of the present study was to determine the antimicrobial resistance trends of respiratory tract pathogens isolated from patients with community-acquired respiratory tract infections (cartis) in crete, greece, over a 4-year period (2009-2012). a total of 588 community-acquired respiratory pathogens were isolated during the study period. streptococcus pneumoniae was the most common organism responsible for 44.4% of cartis, followed by haemophilus influenzae (44.2%) and moraxella catarrhalis ...201424592201
a novel microbiota stratification system predicts future exacerbations in bronchiectasis.although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis, these data are unlikely to provide useful prognostic information at the individual patient level. a system enabling microbiota data to be applied clinically would represent a substantial translational advance.201424592925
a review of invasive haemophilus influenzae disease in the indigenous populations of north america.historically, the highest incidence rates of invasive haemophilus influenzae disease in the world were found in north american and australian indigenous children. although immunization against h. influenzae type b (hib) led to a marked decrease in invasive hib disease in countries where it was implemented, this disease has not been eliminated and its rates in indigenous communities remain higher than in the general north american population. in this literature review, we examined the epidemiolog ...201424598220
nasopharyngeal microbiota in healthy children and pneumonia patients.our study is the first to compare the nasopharyngeal microbiota of pediatric pneumonia patients and control children by 454 pyrosequencing. a distinct microbiota was associated with different pneumonia etiologies. viral pneumonia was associated with a high abundance of the operational taxonomic unit (otu) corresponding to moraxella lacunata. patients with nonviral pneumonia showed high abundances of otus of three typical bacterial pathogens, streptococcus pneumoniae complex, haemophilus influenz ...201424599973
clinical significance and characterization of haemophilus influenzae type b genogroup isolates from urine samples in an adult male population.the occurrence and significance of haemophilus spp. isolated from the genitourinary tract are not well known. herein, we describe the clinical significance and characteristics of haemophilus influenzae type b genogroup strains isolated from genitourinary tract specimens from an adult male veteran patient population and, in particular, their associations with prostatitis and epididymitis.201424599984
[antibiotic resistant genes].genes encoding antibiotic-resistant factors may be exogenous or endogenous. most exogenous genes originate from antibiotic-producing organisms. bacteria can transfer antibiotic-resistant genes among themselves using gene-exchanging systems, such as plasmids, bacteriophages or integrative and conjugative elements. one of the resistance mechanisms is inactivation of antibiotics by modification or decomposition. methicillin-resistant staphylococcus aureus, penicillin-resistant streptococcus pneumon ...201324605547
safety, reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults: a phase i/ii randomized clinical study.new vaccines containing highly conserved streptococcus pneumoniae proteins such as pneumolysin toxoid (dply) and histidine-triad protein d (phtd) are being developed to provide broader protection against pneumococcal disease. this study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults.201424607003
development and validation of high-performance size exclusion chromatography methods to determine molecular size parameters of haemophilus influenzae type b polysaccharides and conjugates.current vaccines against haemophilus influenzae type b (hib) consist of the polyribosyl ribitol phosphate (prp) capsular polysaccharide chemically conjugated to a carrier protein. among the various biological and physical analyses to be performed on these vaccines, the determination of the molecular size of the polysaccharide preparations throughout the conjugation process is particularly relevant. comparison of results from high-performance size exclusion chromatography (hpsec) with those routi ...201424608090
children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants.asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. colonization of neonatal airways with the pathogenic bacterial strains haemophilus influenzae, moraxella catarrhalis, and streptococcus pneumoniae is associated with increased risk of later childhood asthma. we hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy.201424612682
staphylococcus aureus is a major pathogen in severe acute bacterial rhinosinusitis.the purpose of this study was to investigate the epidemiology and microbiology of severe acute bacterial rhinosinusitis in patients admitted to a danish tertiary hospital.201424618628
the toxavapa toxin-antitoxin locus contributes to the survival of nontypeable haemophilus influenzae during infection.nontypeable haemophilus influenzae (nthi) is an opportunistic pathogen that is a common cause of acute and recurrent mucosal infections. one uncharacterized nthi toxin-antitoxin (ta) module, nthi1912-1913, is a host inhibition of growth (higba) homologue. we hypothesized that this locus, which we designated toxavapa, contributed to nthi survival during infection. we deleted toxavapa and determined that growth of the mutant in defined media was not different from the parent strain. we tested the ...201424621787
routine testing for anaerobic bacteria in cerebrospinal fluid cultures improves recovery of clinically significant pathogens.in north america, the widespread use of vaccines targeting haemophilus influenzae type b and streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (csf) specimens has remained largely unchanged. the aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in csf c ...201424622102
metabolic versatility in haemophilus influenzae: a metabolomic and genomic analysis.haemophilus influenzae is a host adapted human pathogen known to contribute to a variety of acute and chronic diseases of the upper and lower respiratory tract as well as the middle ear. at the sites of infection as well as during growth as a commensal the environmental conditions encountered by h. influenzae will vary significantly, especially in terms of oxygen availability, however, the mechanisms by which the bacteria can adapt their metabolism to cope with such changes have not been studied ...201424624122
nod2/rick-dependent β-defensin 2 regulation is protective for nontypeable haemophilus influenzae-induced middle ear infection.middle ear infection, otitis media (om), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable haemophilus influenzae (nthi), the most common om pathogen, via tlr2 signaling. nthi does internalize into the epithelial cells, but its intracellular trafficking and ...201424625812
etiologies and resistance profiles of bacterial community-acquired pneumonia in cambodian and neighboring countries' health care settings: a systematic review (1995 to 2012).community-acquired pneumonia (cap) is one of the most important causes of morbidity and mortality worldwide. etiological data for cambodia is scarce. we aimed to describe the main etiological agents causing cap, and their resistance patterns in cambodia and the greater mekong region.201424626053
human rhinovirus infection during naturally occurring copd exacerbations.human rhinovirus (hrv) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (copd) but its role in determining exacerbation frequency phenotype or the time-course of hrv infection in naturally occurring exacerbations is unknown. sputum samples from 77 patients were analysed by real-time quantitative pcr for both hrv (388 samples), and streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis (89 samples). patients recorded worsening of resp ...201424627537
zinc oxide nanoparticles impair bacterial clearance by macrophages.the extensive development of nanoparticles (nps) and their widespread employment in daily life have led to an increase in environmental concentrations of substances that may pose a biohazard to humans. the aim of this work was to examine the effects of zinc oxide nanoparticles (zno-nps) on the host's pulmonary immune system response to nontypeable haemophilus influenzae (nthi) infection.201424628689
a case of pneumonia caused by legionella pneumophila serogroup 12 and treated successfully with imipenem.the patient was an 83-year-old man hospitalized for haemophilus influenzae pneumonia, who developed recurrent pneumonia after improvement of the initial episode. legionella pneumophila serogroup 12 was isolated from the sputum, accompanied by increased serum antibody titers to l. pneumophila serogroup 12. therefore, the patient was diagnosed as having legionella pneumonia caused by l. pneumophila serogroup 12. case reports of pneumonia caused by l. pneumophila serogroup 12 are rare, and the case ...201424629522
impact of immunization with protein f on pulmonary clearance of nontypeable haemophilus influenzae.nontypeable haemophilus influenzae (nthi) is one of the main aetiologies of childhood bacterial infections as well as exacerbations in copd patients. currently, no licensed nthi vaccine exists. in the present study, we evaluated the potential of the conserved and ubiquitous surface protein haemophilus protein f (pf) as a vaccine candidate. our results show that incubation of nthi with anti-pf antibodies significantly increased the opsonophygocytosis of human promyelocytic leukemia cell line-deri ...201424631068
hospital admission rates for meningitis and septicaemia caused by haemophilus influenzae, neisseria meningitidis, and streptococcus pneumoniae in children in england over five decades: a population-based observational study.infection with haemophilus influenzae, neisseria meningitidis, and streptococcus pneumoniae causes substantial mortality and long-term morbidity in children. we know of no study to assess the long-term trends in hospital admission rates for meningitis and septicaemia caused by these pathogens in children in england. we aimed to do such a study using routinely reported data in england.201424631222
in vitro interaction of pseudomonas aeruginosa with human middle ear epithelial cells.otitis media (om) is an inflammation of the middle ear which can be acute or chronic. acute om is caused by streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis whereas pseudomonas aeruginosa is a leading cause of chronic suppurative otitis media (csom). csom is a chronic inflammatory disorder of the middle ear characterized by infection and discharge. the survivors often suffer from hearing loss and neurological sequelae. however, no information is available regarding the ...201424632826
immunogenicity, safety and reactogenicity of the 10-valent pneumococcal non-typeable haemophilus influenzae protein d conjugate vaccine (phid-cv) in nigerian infants: a randomised trial.the immunogenicity, reactogenicity and safety of the 10- valent pneumococcal non-typeable haemophilus influenzae protein d conjugate vaccine (phid-cv) were evaluated in a cohort of nigerian infants included in a study conducted in mali and nigeria (clinicaltrials.gov identifier: nct00678301).201324633268
recognition of riboflavin and the capsular polysaccharide of haemophilus influenzae type b by antibodies generated to the haptenic epitope d-ribitol.d-ribitol, a five-carbon sugar alcohol, is an important metabolite in the pentose phosphate pathway; it is an integral part of riboflavin (vitamin b2) and cell wall polysaccharides in most gram-positive and a few gram-negative bacteria. antibodies specific to d-ribitol were generated in new zealand white rabbits by using reductively aminated d-ribose-bsa conjugate as the immunogen. maldi-tof and amino group analyses of ribitol-bsa conjugate following 120 h reaction showed ~27-30 mol of ribitol c ...201424643482
impact of staphylococcus aureus on pathogenesis in polymicrobial infections.polymicrobial infections involving staphylococcus aureus exhibit enhanced disease severity and morbidity. we reviewed the nature of polymicrobial interactions between s. aureus and other bacterial, fungal, and viral cocolonizers. microbes that were frequently recovered from the infection site with s. aureus are haemophilus influenzae, enterococcus faecalis, pseudomonas aeruginosa, streptococcus pneumoniae, corynebacterium sp., lactobacillus sp., candida albicans, and influenza virus. detailed an ...201424643542
risk of invasive haemophilus influenzae infection during pregnancy and association with adverse fetal outcomes.unencapsulated haemophilus influenzae frequently causes noninvasive upper respiratory tract infections in children but can also cause invasive disease, especially in older adults. a number of studies have reported an increased incidence in neonates and suggested that pregnant women may have an increased susceptibility to invasive unencapsulated h. influenzae disease.201424643602
the influence of stents on microbial colonization of the airway in children after slide tracheoplasty: a 14-year single-center experience.this study describes the microbial colonization profile of the airway in children after slide tracheoplasty (stp) with and without stents, and compares colonization to children undergoing cardiothoracic surgical procedures without airway related disease.201524648152
[in vitro activity of sitafloxacin against clinical isolates in 2012].in vitro activity of sitafloxacin (stfx) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between january and december 2012, at different healthcare facilities in japan was evaluated. a total of 1,620 isolates including aerobic and anaerobic organisms were available for the susceptibility testing using the microbroth dilution methods recommended by clinical and laboratory standards institute. the minimum inhibitory concentration of stfx at which ...201324649797
[susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].from october 2006 to september 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. the isolated bacteria were: staphylococcus aureus 64, streptococcus pneumoniae 96, ...201324649798
the challenges and successes of implementing a sustainable antimicrobial resistance surveillance programme in nepal.antimicrobial resistance (amr) is a major global public health concern and its surveillance is a fundamental tool for monitoring the development of amr. in 1998, the nepalese ministry of health (moh) launched an infectious disease (id) programme. the key components of the programme were to establish a surveillance programme for amr and to develop awareness among physicians regarding amr and rational drug usage in nepal.201424650008
the inflammasome adaptor asc contributes to multiple innate immune processes in the resolution of otitis media.this study was designed to understand the contribution of the inflammasome and il-1β activation in otitis media (om). we examined the middle ear (me) response to non-typeable haemophilus influenzae (nthi) in wild type (wt) mice using gene microarrays and a murine model of acute om. expression of members of the nod domain-like receptor family of inflammasome genes was significantly up-regulated early in nthi infection of the me, potentially activating specific downstream regulatory cascades that ...201524652041
pharmacokinetic modelling of serum and bronchial concentrations for clarithromycin and telithromycin, and site-specific pharmacodynamic simulation for their dosages.clinical pharmacokinetic profiles of clarithromycin and telithromycin in bronchopulmonary sites have not been fully characterized. this study aimed to describe in more detail the pharmacokinetics of the two macrolides in epithelial lining fluid (elf) of human bronchi and to evaluate their pharmacodynamic target attainment at this site.201424661290
a fine-tuned interaction between trimeric autotransporter haemophilus surface fibrils and vitronectin leads to serum resistance and adherence to respiratory epithelial cells.haemophilus influenzae type b (hib) escapes the host immune system by recruitment of the complement regulator vitronectin, which inhibits the formation of the membrane attack complex (mac) by inhibiting c5b-c7 complex formation and c9 polymerization. we reported previously that hib acquires vitronectin at the surface by using haemophilus surface fibrils (hsf). here we studied in detail the interaction between hsf and vitronectin and its role in the inhibition of mac formation and the invasion of ...201424664511
guidelines for the management of suspected and confirmed bacterial meningitis in canadian children older than one month of age.the incidence of bacterial meningitis in infants and children has decreased since the routine use of conjugated vaccines targeting haemophilus influenzae type b, streptococcus pneumoniae and neisseria meningitidis. however, this infection continues to be associated with considerable mortality and morbidity if not treated effectively with empirical antimicrobial therapy. diagnosis still rests on clinical signs and symptoms, and cerebrospinal fluid analysis. this position statement outlines the ra ...201424665226
activation of innate immune responses by haemophilus influenzae lipooligosaccharide.a gram-negative pathogen haemophilus influenzae has a truncated endotoxin known as lipooligosaccharide (los). recent studies on h. influenzae los highlighted its structural and compositional implications for bacterial virulence; however, the role of los in the activation of innate and adaptive immunity is poorly understood. thp-1 monocytes were stimulated with either lipopolysaccharide (lps) from escherichia coli or los compounds derived from h. influenzae eagan, rd, and rd lic1 lpsa strains. ce ...201424671554
characterization of lactate utilization and its implication on the physiology of haemophilus influenzae.haemophilus influenzae is a gram-negative bacillus and a frequent commensal of the human nasopharynx. earlier work demonstrated that in h. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. to further gain insight into lactate utilization of the non-typeable (nthi) isolate 2019 and laboratory prototype strain rd kw20, deletion mutants of the l-lactate dehydrogenase (lctd) and permease (lctp) were generated and characterized. it is sh ...201424674911
in vitro selection of rna aptamers directed against protein e: a haemophilus influenzae adhesin.protein e (pe) of haemophilus influenzae is a highly conserved ubiquitous surface protein involved in adhesion to and activation of epithelial cells. the host proteins-vitronectin, laminin, and plasminogen are major targets for pe-dependent interactions with the host. to identify novel inhibitory molecules of pe, we used an in vitro selection method based on systematic evolution of ligands by exponential enrichment known as selex in order to select 2'f-modified rna aptamers that specifically bin ...201424682699
the hospitalist perspective on treatment of community-acquired bacterial pneumonia.community-acquired bacterial pneumonia (cabp) is an important health care concern in the united states and worldwide, and is associated with significant morbidity, mortality, and health care expenditure. streptococcus pneumoniae is the most frequent causative pathogen of cabp. other common pathogens include staphylococcus aureus, haemophilus influenzae, enterobacteriaceae, legionella pneumophila, mycoplasma pneumoniae, and chlamydophila pneumoniae. however, in clinical practice, the causative pa ...201424685965
impaired innate immune alveolar macrophage response and the predilection for copd exacerbations.alveolar macrophages (am) in copd have fundamentally impaired responsiveness to toll-like receptor 2 (tlr2) and tlr4 ligands of non-typeable haemophilus influenzae (nthi). however, the contribution of innate immune dysfunction to exacerbations of copd is unexplored. we hypothesised that impaired innate am responses in copd extend beyond nthi to other pathogens and are linked with copd exacerbations and severity.201424686454
structural determinants of the interaction between the haemophilus influenzae hap autotransporter and fibronectin.haemophilus influenzae is a gram-negative cocco-bacillus that initiates infection by colonizing the upper respiratory tract. hap is an h. influenzae serine protease autotransporter protein that mediates adherence, invasion and microcolony formation in assays with human epithelial cells and is presumed to facilitate the process of colonization. additionally, hap mediates adherence to fibronectin, laminin and collagen iv, extracellular matrix (ecm) proteins that are present in the respiratory trac ...201424687948
isolation, structure elucidation and antibacterial activity of a new tetramic acid, ascosetin.the ever-increasing bacterial resistance to clinical antibiotics is making many drugs ineffective and creating significant treatment gaps. this can be only circumvented by the discovery of antibiotics with new mechanisms of action. we report here the identification of a new tetramic acid, ascosetin, from an ascomycete using the staphylococcus aureus fitness test screening method. the structure was elucidated by spectroscopic methods including 2d nmr and hrms. relative stereochemistry was determi ...201424690911
expression and purification of haemophilus influenzae rhomboid intramembrane protease glpg for structural studies.rhomboid proteases are membrane-embedded proteases that cleave peptide bonds of transmembrane proteins. they play a variety of roles in cell signaling events. the rhomboid protease glpg from haemophilus influenzae (higlpg) is a canonical form of rhomboid protease having six transmembrane segments. in this unit, detailed protocols are presented for optimization of higlpg expression using the arabad promotor system in the pbad vector. the parameters for optimization include concentration of induci ...201424692018
bacterial vaccines and antibiotic resistance.spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. since resistance frequently is horizontally transferred it will be difficult to generat ...201424694025
pneumococcal conjugate vaccines for preventing otitis media.acute otitis media (aom) is a very common respiratory infection in early infancy and childhood. the marginal benefits of antibiotics for aom in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual costs associated with otitis media (om) have prompted a search for effective vaccines to prevent aom.201424696098
classification, identification, and clinical significance of haemophilus and aggregatibacter species with host specificity for humans.the aim of this review is to provide a comprehensive update on the current classification and identification of haemophilus and aggregatibacter species with exclusive or predominant host specificity for humans. haemophilus influenzae and some of the other haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. new sp ...201424696434
bisphosphonate related osteonecrosis of the jaw: a study of 18 cases associated with fungal infection.osteonecrosis of the jaw (onj) is a serious complication associated with oral and intravenous bisphosphonate therapy. its pathogenesis is not well understood and its management is difficult. microbiological investigations have detected a variety of oral pathogens such as actinomyces, enterococcus, candida albicans, aspergillus, haemophilus influenzae, alpha-hemolytic streptococci, lactobacillus, enterobacter, and klebsiella pneumoniae. to better treat it, it is important to understand its causes ...201424696686
detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations.detection of either viral or bacterial pathogens is associated with wheezing in children; however, the influence of both bacteria and viruses on illness symptoms has not been described.201424698319
antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections.to address the problem of limited efficacy of existing antibiotics in the treatment of bacterial biofilm, it is necessary to find alternative remedies. one candidate could be hyaluronic acid; this study therefore aimed to evaluate the in vitro antiadhesive and antibiofilm activity of hyaluronic acid toward bacterial species commonly isolated from respiratory infections. interference exerted on bacterial adhesion was evaluated by using hep-2 cells, while the antibiofilm activity was assessed by m ...201424698341
haemophilus influenzae: recent advances in the understanding of molecular pathogenesis and polymicrobial infections.non-typeable haemophilus influenzae (nthi) is a human-specific mucosal pathogen and one of the most common causes of bacterial infections in children and patients with chronic obstructive pulmonary disease. it is also frequently found in polymicrobial superinfections. great strides have recently been made in the understanding of the molecular mechanisms underlying nthi pathogenesis.201424699388
safety and immunogenicity of an investigational vaccine containing two common pneumococcal proteins in toddlers: a phase ii randomized clinical trial.to provide broader protection against pneumococcal disease, new vaccines containing conserved streptococcus pneumoniae proteins are being developed. this study assessed the safety, reactogenicity and immunogenicity of four formulations containing pneumococcal proteins pneumolysin toxoid (dply) and histidine triad protein (phtd) in toddlers.201424699466
[antimicrobial spectrum of ceftaroline. in vitro activity against methicillin-resistant staphylococci].because of the increase in bacterial resistance, there is a need for new antimicrobial agents. in particular, staphylococcus aureus is a frequent cause of severe infections and has an extraordinary capacity to develop antibiotic multiresistance, including resistance to glycopeptides, linezolid, and daptomycin. although the incidence of methicillin-resistant s. aureus (mrsa) seems to have stabilized in the last few years, its wide dissemination in healthcare settings and in the community is a cau ...201424702973
[ceftaroline breakpoints].ceftaroline is a new cephalosporin for parenteral use. notable among its microbiological properties is its ability to inhibit penicillin-binding protein 2a of methicillin-resistant staphylococcus aureus and its good in vitro activity against several microorganisms of clinical interest. the european committee of antimicrobial susceptibility testing (eucast) has defined both epidemiological breakpoints (defining wild-type populations that lack known acquired mechanisms of resistance) and clinical ...201424702975
genome sequencing of disease and carriage isolates of nontypeable haemophilus influenzae identifies discrete population structure.one of the main hurdles for the development of an effective and broadly protective vaccine against nonencapsulated isolates of haemophilus influenzae (nthi) lies in the genetic diversity of the species, which renders extremely difficult the identification of cross-protective candidate antigens. to assess whether a population structure of nthi could be defined, we performed genome sequencing of a collection of diverse clinical isolates representative of both carriage and disease and of the divers ...201424706866
are airways structural abnormalities more frequent in children with recurrent lower respiratory tract infections?we report bronchoscopic changes observed in children with recurrent lower airways infections (rlai) and findings in control children undergoing bronchoscopy for causes other than rlai.201424709380
differential susceptibility of invasive haemophilus influenzae serotype a and serotype b to ampicillin and other commonly prescribed antibiotics.haemophilus influenzae serotype a (hia) has become an important pathogen in the post-h. influenzae serotype b (hib) vaccine era. antibiotic resistance in h. influenzae is a global phenomenon, but few studies have looked at antibiotic resistance profiles with regard to serotype. invasive hia (n = 157), noninvasive hia (n = 2) and invasive hib (n = 42) collected over the last two decades from three canadian provinces were examined for resistance to several commonly prescribed antibiotics, and sequ ...201424712310
oropharyngeal colonization by nontypeable haemophilus influenzae among healthy children attending day care centers.haemophilus influenzae colonizes the upper respiratory tract and can spread causing otitis and sinusitis. this work aimed to study the oropharyngeal carriage rate in healthy <5-year-old children attending day care centers in oviedo, spain in two consecutive years (january to march 2004-2005). the carriage rate was 42% (400/960) and highly variable among centers (range, 12% to 83%). isolates were mainly identified as nontypeable h. influenzae (nthi, 99%). epidemiologically, 127 different genotype ...201424716536
[background factors in the detection of drug-resistant bacteria in adult patients with acute rhinosinusitis].in the treatment of adult patients with acute rhinosinusitis, it has been assumed that subjects over 65 years of age or living with children attending a day nursery, are at higher risk for infection with drug-resistant bacteria. however there are few reports which have discussed the relationship between those risk factors and adult patients with acute rhinosinusitis. i investigated the association between adult patients with acute rhinosinusitis living with children attending a day nursery and g ...201424720161
small substrate transport and mechanism of a molybdate atp binding cassette transporter in a lipid environment.embedded in the plasma membrane of all bacteria, atp binding cassette (abc) importers facilitate the uptake of several vital nutrients and cofactors. the abc transporter, molbc-a, imports molybdate by passing substrate from the binding protein mola to a membrane-spanning translocation pathway of molb. to understand the mechanism of transport in the biological membrane as a whole, the effects of the lipid bilayer on transport needed to be addressed. continuous wave-electron paramagnetic resonance ...201424722984
necrotizing fasciitis caused by haemophilus influenzae type b in a patient with rectal cancer treated with combined bevacizumab and chemotherapy: a case report.recently, necrotizing fasciitis has been reported in patients treated with bevacizumab, usually secondary to wound healing complications, gastrointestinal perforations, or fistula formation. the risk of invasive haemophilus influenzae type b infection is significantly increased in immunocompromised hosts. however, necrotizing fasciitis due to haemophilus influenzae type b in a patient treated with combined bevacizumab and chemotherapy has not been previously reported.201424725844
bacterial and viral etiology in hospitalized community acquired pneumonia with molecular methods and clinical evaluation.polymerase chain reaction (pcr) method has improved the diagnosis rates for patients with community-acquired pneumonia (cap). we aimed to evaluate the bacterial and viral etiology of hospitalized cap cases and compare clinical and laboratory findings of patients with pure bacterial and bacterial and viral (mixed) infections.201424727518
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