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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
epidemiology and risk factors for pneumonia severity and mortality in bangladeshi children <5 years of age before 10-valent pneumococcal conjugate vaccine introduction.pneumonia is the leading infectious cause of morbidity and mortality in young children in bangladesh. we present the epidemiology of pneumonia in bangladeshi children <5 years before 10-valent pneumococcal conjugate vaccine introduction and investigate factors associated with disease severity and mortality.201627927201
hospitalizations for pneumonia, invasive diseases and otitis in tuscany (italy), 2002-2014: which was the impact of universal pneumococcal pediatric vaccination?streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. since 2008 in tuscany, central italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the tuscan population on hospitalizations potentially caused by s. pneumoniae, during ...201727925848
markerless genome editing in competent streptococci.selective markers employed in classical mutagenesis methods using natural genetic transformation can affect gene expression, risk phenotypic effects, and accumulate as unwanted genes during successive mutagenesis cycles. in this chapter, we present a protocol for markerless genome editing in streptococcus mutans and streptococcus pneumoniae achieved with an efficient method for natural transformation. high yields of transformants are obtained by combining the unimodal state of competence develop ...201727924598
natural transformation of oral streptococci by use of synthetic pheromones.the discovery that streptococcus pneumoniae uses a competence-stimulating peptide (csp) to induce competence for natural transformation, and that other species of the mitis and the anginosus streptococcal groups use a similar system, has expanded the tools to explore gene function and regulatory pathways in streptococci. two other classes of pheromones have been discovered since then, comprising the bacteriocin-inducing peptide class found in streptococcus mutans (also named csp, although differ ...201727924597
synthesis and antibacterial activity of novel lincomycin derivatives. ii. exploring (7s)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives.the synthesis and antibacterial activity of (7s)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives are described. these derivatives were mainly prepared by the mitsunobu reaction of 2,3,4-tris-o-(trimethylsilyl)lincomycin and the corresponding thiols. exploring structure-activity relationships of the substituent at the 5 position of a thiadiazole ring revealed that compounds with the ortho substituted phenyl group showed improved antibacterial activities against streptococcus p ...201627924113
c-type lectin mincle recognizes glucosyl-diacylglycerol of streptococcus pneumoniae and plays a protective role in pneumococcal pneumonia.among various innate immune receptor families, the role of c-type lectin receptors (clrs) in lung protective immunity against streptococcus pneumoniae (s. pneumoniae) is not fully defined. we here show that mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. moreover, s. pneumoniae directly triggered mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (glc-dag ...201627923071
adhesion and invasion of streptococcus pneumoniae to primary and secondary respiratory epithelial cells.the interaction between streptococcus pneumoniae (s. pneumoniae) and the mucosal epithelial cells of its host is a prerequisite for pneumococcal disease development, yet the specificity of this interaction between different respiratory cells is not fully understood. in the present study, three areas were examined: i) the capability of the encapsulated s. pneumoniae serotype 3 strain (wu2) to adhere to and invade primary nasal‑derived epithelial cells in comparison to primary oral‑derived epithel ...201727922699
viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances ip-10: a translational study.mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. in this study, microrna, mrna and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with influenza virus a/h1n1 and/or streptococcus pneumoniae. we observed that the in-vitro co-infection synergistically increased interferon-γ-induced pr ...201627922126
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
trivalent pneumococcal protein vaccine protects against experimental acute otitis media caused by streptococcus pneumoniae in an infant murine model.currently licensed serotype-based pneumococcal vaccines are effective in preventing invasive pneumococcal diseases, but less effective in preventing non-bacteremic pneumonia and acute otitis media (aom). we previously reported that a trivalent pneumococcal protein recombinant vaccine (pprv) protected against pneumonia in a murine model. here we evaluated pprv protection against aom in an infant murine model.201727919628
drivers of airborne human-to-human pathogen transmission.airborne pathogens - either transmitted via aerosol or droplets - include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza a viruses, mycobacterium tuberculosis, streptococcus pneumoniae, and bordetella pertussis. emerging zoonotic pathogens, for example, mers coronavirus, avian influenza viruses, coxiella, and francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. here, we synthesize in ...201727918958
ceftaroline activity against multidrug-resistant streptococcus pneumoniae from u.s. medical centers (2014) and molecular characterization of a single ceftaroline nonsusceptible isolate.streptococcus pneumoniae isolates (2,614) were collected from patients at 135 u.s. medical centers during 2014. isolates were evaluated for multidrug resistance to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. a single isolate (853008) demonstrated a ceftaroline nonsusceptible minimal inhibitory concentration (mic) value, and it was subjected to molecular characterization. ceftaroline (mic50/90, ≤0.015/0.12 μg/ml) was eightfold more potent ...201627918694
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
modular architecture and unique teichoic acid recognition features of choline-binding protein l (cbpl) contributing to pneumococcal pathogenesis.the human pathogen streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (cbps) attached to phosphorylcholine (pcho) moieties from cell-wall teichoic acids. by a combination of x-ray crystallography, nmr, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein l (cbpl) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. cbpl is a ve ...201627917891
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
development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains of streptococcus pneumoniae.streptococcus pneumoniae is a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacterium s. pneumoniae that are conjugated to a carrier protein. three pneumococcal conjugated vaccin ...201627917323
a 32-year study of the effect of pneumococcal vaccines on invasive streptococcus pneumoniae disease.worldwide, streptococcus pneumoniae commonly causes community-acquired pneumonia, meningitis, septicemia and otitis media. invasive pneumococcal infection (ipd) represents the most serious presentation, occurs in approximately 1 in 4 cases and engenders case fatality rates (cfr) in pneumonia of 20-25% and meningitis of 35-40%. we investigated ipd for 32 years in an american city to assess the effect of differing pneumococcal vaccines on serotype occurrence and cfr among children and adults.201627916211
in vitro and in vivo biofilm formation by pathogenic streptococci.this manuscript presents novel approaches to grow and evaluate streptococcal biofilm formation using the human respiratory pathogen streptococcus pneumoniae (the pneumococcus) as the main model organism on biological surfaces in vitro and in vivo. most biofilm models are based on growth on abiotic surfaces, which is relevant for many pathogens whose growth on surfaces or medical devices is a major cause of disease transmission and infections, especially in hospital environments. however, most in ...201727914087
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
invasive pneumococcal disease: from a tertiary care hospital in the post-vaccine era.a breakthrough infection occurring with 13-valent pneumococcal conjugate vaccine (pcv13) in turkey are previously described. a breakthrough infection is defined as ipd in a child who had received ≥ 1 pcv-7 or pcv-13 and for which the pneumococcal isolate was a vaccine serotype. during one year period, among 6 patients with invasive pneumococcal infection, 2 patients were considered to have a vaccine failure with serotype 19f. antibiotic resistance results were remarkable; macrolide resistance we ...201627905836
evidence that pneumococcal walk is regulated by stkp through protein-protein interaction.walrk is the only two-component regulatory system essential for viability in streptococcus pneumoniae. despite its importance, the biological role of this system is not well understood. however, previous studies have shown that it has a crucial role in controlling pneumococcal cell division. considerable efforts have been made to understand how the walrk system is regulated, but no signal(s) sensed by the walk histidine kinase has been identified so far. here, we provide evidence that the serine ...201727902439
overexpression of the fratricide immunity protein comm leads to growth inhibition and morphological abnormalities in streptococcus pneumoniae.the important human pathogen streptococcus pneumoniae is a naturally transformable species. when developing the competent state, it expresses proteins involved in dna uptake, dna processing and homologous recombination. in addition to the proteins required for the transformation process, competent pneumococci express proteins involved in a predatory dna acquisition mechanism termed fratricide. this is a mechanism by which the competent pneumococci secrete a muralytic fratricin termed cbpd, which ...201727902435
n-acetylglucosamine-mediated expression of naga and nagb in streptococcus pneumoniae.in this study, we have explored the transcriptomic response of streptococcus pneumoniae d39 to n-acetylglucosamine (nag). transcriptome comparison of s. pneumoniae d39 wild-type grown in chemically defined medium (cdm) in the presence of 0.5% nag to that grown in the presence of 0.5% glucose revealed elevated expression of many genes/operons, including naga, nagb, manlmn, and nanp. we have further confirmed the nag-dependent expression of naga, nagb, manlmn, and nanp by β-galactosidase assays. n ...201627900287
microbiological profile of corneal ulcer cases diagnosed in a tertiary care ophthalmological institute in nepal.corneal ulcer, a major cause of monocular blindness in developing countries has consistently been listed as the major cause of blindness and visual disability in many of the developing nations in asia, africa and the middle east, ranking second only to cataract. this study was carried out to determine the microbiological profile of corneal ulcer cases diagnosed among patients visiting tilganga institute of ophthalmology (tio), nepal.201627899093
impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo.short chain fatty acids (scfas) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. this is of particular concern in light of the attractiveness of developing scfa-mediated therapies and considering that scfas work as inhibitors of histone deacetylases which are known to interfere with host defenses. here we show that propionate, one of the main scfas, dampens the response of innate immune cells to mic ...201627897220
making standards for quantitative real-time pneumococcal pcr.quantitative lyta pcr is often performed using in-house standards. we hypothesised equivalence when measuring a standard suspension of streptococcus pneumoniae by colony-forming-units (cfu) or genome-copies. median (iqr) ratio of cfu/genome-copies was 0.19 (0.1-1.2). genome-copies were less variable than cfu, but the discrepancy between the methods highlights challenges with absolute quantification.201427896138
a trial of a 7-valent pneumococcal conjugate vaccine in hiv-infected adults.streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (hiv) infection, particularly in africa. prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed.201627895845
protection against streptococcus pneumoniae invasive pathogenesis by a protein-based vaccine is achieved by suppression of nasopharyngeal bacterial density during influenza a virus coinfection.an increase in streptococcus pneumoniae nasopharynx (np) colonization density during a viral coinfection initiates pathogenesis. to mimic natural s. pneumoniae pathogenesis, we commensally colonized the nps of adult c57bl/6 mice with s. pneumoniae serotype (st) 6a or 8 and then coinfected them with mouse-adapted h1n1 influenza a virus (pr/8/34). s. pneumoniae established effective commensal colonization, and influenza virus coinfection caused s. pneumoniae np density to increase, resulting in ba ...201727895132
influenza and rhinovirus viral load and disease severity in upper respiratory tract infections.the role of viral load in respiratory viral infection is unclear. it is proposed that the viral load of some, but not all respiratory viruses correlate with disease severity.201727893998
host-derived extracellular rna promotes adhesion of streptococcus pneumoniae to endothelial and epithelial cells.streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. the infection process involves bacterial cell surface receptors, which interact with host extracellular matrix components to facilitate colonization and dissemination of bacteria. here, we investigated the role of host-derived extracellular rna (erna) in the process of pneumococcal alveolar epithelial cell infection. our study demonstrates that erna dose-dependently increased s. pneumoniae invasion of alveolar e ...201627892961
streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis.streptococcus pneumoniae is a leading cause of bacterial pneumonia and is the principal cause of morbidity and mortality worldwide. previous studies suggested that excessive activation of neutrophils results in the release of neutrophil elastase, which contributes to lung injury in severe pneumonia. although both pneumococcal virulence factors and neutrophil elastase contribute to the development and progression of pneumonia, there are no studies analysing relationships between these factors. he ...201627892542
production and purification of an untagged recombinant pneumococcal surface protein a (pspa4pro) with high-purity and low endotoxin content.streptococcus pneumoniae is the main cause of pneumonia, meningitis, and other conditions that kill thousands of children every year worldwide. the replacement of pneumococcal serotypes among the vaccinated population has evidenced the need for new vaccines with broader coverage and driven the research for protein-based vaccines. pneumococcal surface protein a (pspa) protects s. pneumoniae from the bactericidal effect of human apolactoferrin and prevents complement deposition. several studies in ...201727889801
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
development of a novel engineered antibody targeting neisseria species.a neissaria bacterial pilus sugar, bacillosamine, was synthesized and, for the first time, used as a probe to screen a single-chain variable fragment (scfv).201727888365
enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine.streptococcus pneumoniae and influenza are the world's foremost bacterial and viral respiratory pathogens. we have previously described a γ-irradiated influenza a virus (γ-flu) vaccine that provides cross-protective immunity against heterosubtypic infections. more recently, we reported a novel non-adjuvanted γ-irradiated s pneumoniae (γ-pn) vaccine that elicits serotype-independent protection. considering the clinical synergism of both pathogens, combination of a serotype-independent pneumococca ...201727885052
systemic immunization with rpotd reduces streptococcus pneumoniae nasopharyngeal colonization in mice.streptococcus pneumoniae (pneumococcus) is a human pathogen that can cause otitis media, pneumonia and, in severe cases, meningitis and bacteremia. the pneumococcus expresses potd, a protein belonging to the polyamines transporter complex called potabcd. potd is a membrane-associated protein that binds polyamines and has been shown to be important for virulence. in this work we demonstrate that subcutaneous immunization with rpotd reduces the bacterial load in the nasal tissue of mice, following ...201727884476
synthesis of the biological repeating unit of streptococcus pneumoniae serotype 23f capsular polysaccharide.an efficient synthesis of the 3-aminopropyl glycoside of the biological repeating unit of streptococcus pneumoniae serotype 23f capsular polysaccharide (cps) was accomplished. the synthetic target contained a tetrasaccharide with a phosphoglycerol branch. its oligosaccharide backbone was assembled via linear glycosylation, and the challenging β-rhamnosyl linkage in its structure was achieved stereospecifically through naphthylmethyl-assisted intramolecular aglycon delivery (iad). the remaining 1 ...201627883156
candida glabrata pneumonia in a patient with chronic obstructive pulmonary disease.pneumonia remains an important cause of morbidity and mortality among infectious diseases. streptococcus pneumoniae and viruses are the most common cause of pneumonia. candidiasis in such patients has been associated with haemodialysis, fungal colonization, exposure to broad-spectrum antibiotics, intensive care unit (icu) hospitalization, and immunocompromised patients. the most common cause of infection is c. albicans. the case presented here is of a 66-year-old male patient diagnosed with c. g ...201627882253
impact of pneumococcal conjugate vaccines on selected head and neck infections in hospitalized israeli children.streptococcus pneumoniae is a major pathogen of pediatric head and neck infections (hnis), for example, acute otitis media (aom), acute mastoiditis, acute bacterial sinusitis and meningitis. the aim of this study was to characterize the epidemiology of pneumococcal hnis (phnis) before, during and after the introduction of pneumococcal conjugate vaccines (pcvs).201727879558
preparation and immunogenicity of gold glyco-nanoparticles as antipneumococcal vaccine model.nanotechnology-based fully synthetic carbohydrate vaccines are promising alternatives to classic polysaccharide/protein conjugate vaccines. we have prepared gold glyco-nanoparticles (gnp) bearing two synthetic carbohydrate antigens related to serotypes 19f and 14 of streptococcus pneumoniae and evaluated their immunogenicity in vivo.201727879152
doping polypyrrole films with 4-n-pentylphenylboronic acid to enhance affinity towards bacteria and dopamine.here we demonstrate the use of a functional dopant as a fast and simple way to tune the chemical affinity and selectivity of polypyrrole films. more specifically, a boronic-functionalised dopant, 4-n-pentylphenylboronic acid (pba), was used to provide to polypyrrole films with enhanced affinity towards diols. in order to prove the proposed concept, two model systems were explored: (i) the capture and the electrochemical detection of dopamine and (ii) the adhesion of bacteria onto surfaces. the c ...201627875555
in vitro activity of ceftaroline tested against isolates from the asia-pacific region and south africa (2011).during 2011, 29 medical centres in eight asia-pacific countries and south africa submitted a total of 3697 bacterial pathogens for surveillance testing, of which 39.1% were from respiratory tract, 27.9% from skin and skin-structure, 19.2% from bloodstream, 5.1% from urinary tract and 8.7% from miscellaneous infection types. meticillin-resistant staphylococcus aureus (mrsa) constituted 38.9% of the 1114 s. aureus. the mrsa rate was 53.5% for respiratory tract infections and 31.8% for skin and ski ...201427873727
high burden of antimicrobial drug resistance in asia.the rapid development of antimicrobial resistance among micro-organisms is a serious public health concern. moreover, the dissemination of antibiotic-resistant bacteria makes this issue a global problem, and asia is no exception. for example, since new delhi metallo-β-lactamase (ndm)-producing enterobacteriaceae were identified in india, further spread of ndm has become a worldwide threat. however, the epidemiology of antibiotic-resistant bacteria in asia may be different to other regions, and c ...201427873720
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
roles of the essential protein ftsa in cell growth and division in streptococcus pneumoniae.streptococcus pneumoniae is an ovoid-shaped gram-positive bacterium that grows by carrying out peripheral and septal peptidoglycan (pg) synthesis, analogous to model bacilli such as escherichia coli and bacillus subtilis in the model bacilli, ftsz and ftsa proteins assemble into a ring at midcell and are dedicated to septal pg synthesis, but not peripheral pg synthesis; hence inactivation of ftsz or ftsa results in long filamentous cells unable to divide. here we demonstrate that ftsa and ftsz c ...201627872183
pharmacokinetic-pharmacodynamic evaluation of gepotidacin against gram-positive organisms using data from murine infection models.gepotidacin (formerly called gsk2140944) is a novel triazaacenaphthylene bacterial topoisomerase inhibitor with in vitro activity against conventional and biothreat pathogens, including staphylococcus aureus and streptococcus pneumoniae using neutropenic murine thigh and lung infection models, the pharmacokinetics-pharmacodynamics (pk-pd) of gepotidacin against s. aureus and s. pneumoniae were characterized. candidate models were fit to single-dose pk data from uninfected mice (for doses of 16 t ...201727872075
antimicrobial activity of zabofloxacin against clinically isolated streptococcus pneumoniae.zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. in this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant streptococcus pneumoniae. among the fluoroquinolone compounds, zabofloxacin showed the most potent in vitro activity against clinical isolates of penicillin-sensitive s. pneumoniae (minimum inhibitory concentration, mic90: 0.03 mg/l) and penicillin-resistant s. pneumoniae ...201627869677
persistence of antimicrobial resistance in respiratory streptococci.to assess whether persistence of antimicrobial resistance (i.e. non-susceptible resistance status) after treatment with penicillins or cephalosporins versus macrolides or tetracyclines differs and to compare the results obtained using routinely collected data with findings reported in prospective studies.201727865986
pneumococcal pep27 mutant immunization stimulates cytokine secretion and confers long-term immunity with a wide range of protection, including against non-typeable strains.streptococcus pneumoniae is comprised of more than 90 serotypes and is the major causative agent of pneumonia, which results in over 1million deaths worldwide every year. currently available injectable vaccines can protect against only 13-23 serotypes, and result in decrease of colonization against vaccine serotypes. however, they are neither effective for inhibition of non-vaccine serotypes colonization nor inhibition against initial colonization in the nasopharynx against various serotypes. th ...201627865564
evaluation of a rapid antigen test for detection of streptococcus pneumoniae in cerebrospinal fluid.detection of streptococcus pneumoniae antigen in cerebrospinal fluid (csf) using lateral flow immunochromatography tests (icts) is an effective, rapid and low-cost method to diagnose pneumococcal meningitis. this study evaluated the diagnostic accuracy of the uni-gold ict to detect pneumococcal antigen in csf specimens, compared with gold standard bacteriology and quantitative real-time pcr (qpcr) testing. csf specimens (n=69) from patients with suspected bacterial meningitis were included in th ...201627864448
invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era.pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (ipi). data on ipi in this population are scarce. to our knowledge, this is the first study describing the epidemiology of ipi among pediatric transplant recipients in the pneumococcal conjugate vaccine (pcv) era.201727862712
cord blood streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in papua new guinea.in areas where streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. we aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. cord blood mononuclear cells (cbmc) of 84 papua new guinean (png; high endemic) and 33 australian (aus; low endemic) newborns were stimu ...201727859014
a non-human primate model of severe pneumococcal pneumonia.streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. a non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia.201627855182
evaluation of chest radiography, lyta real-time pcr, and other routine tests for diagnosis of community-acquired pneumonia and estimation of possible attributable fraction of pneumococcus in northern togo.streptococcus pneumoniae (spn) is a leading cause of community-acquired pneumonia (cap), yet existing diagnostic tools remain inadequate. we aimed to evaluate laboratory and radiological methods for detecting pneumococcal aetiology in cap patients and to estimate spn prevalence in this group. all-aged patients hospitalized with clinically defined cap in northern togo were enrolled during 2010-2013. latent class analysis pooled results of semi-automated blood culture (sabc), whole blood lyta real ...201727852346
emergence of multidrug-resistant pneumococcal serotype 35b among children in the united states.streptococcus pneumoniae serotype 35b is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. an increase in the proportion of multidrug-resistant (mdr) 35b isolates has recently been reported. the genetic events contributing to the emergence of mdr serotype 35b are unknown. the sequence type (st) composition of 78 serotype 35b isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with o ...201727847379
multiplex urinary antigen detection for 13 streptococcus pneumoniae serotypes improves diagnosis of pneumococcal pneumonia in south african hiv-infected adults.a serotype-specific urinary antigen detection (uad) assay for 13 serotypes included in the pneumococcal conjugate vaccine (pcv13) was recently reported as a useful diagnostic tool for pneumococcal pneumonia. we aimed to assess the diagnostic accuracy of the uad in hiv-infected south african adults. urine specimens from a well-defined cohort of hiv-infected south african adults with pneumonia were evaluated retrospectively in the uad assay. pneumonia was considered pneumococcal if either sputum g ...201727847374
pyomyositis caused by streptococcus pneumoniae after allogeneic hematopoietic stem cell transplantation.pyomyositis is classified into two main types: tropical and non-tropical. non-tropical pyomyositis occurs among various immunocompromised patients, and staphylococcus aureus has been reported as the most common pathogen. pyomyositis caused by streptococcus pneumoniae is uncommon, and has not been previously reported after allogeneic hematopoietic stem cell transplantation (allo-hsct). here, we report a unique case with pyomyositis caused by s. pneumoniae in the bilateral erector spinae muscles 3 ...201727847295
molecular characterization of a single-chain antibody variable fragment (scfv) specific for pspa from streptococcus pneumoniae.streptococcus pneumoniae is a major infectious agent responsible for pneumonia, otitis media, sepsis and meningitis. pneumococcal surface protein a (pspa) is a well-characterized virulence factor localized on the surface and a target for vaccine development. in this study, we screened a single-chain antibody variable fragment (scfv) using phage display from a human synthetic library to select a clone 2b11. affinity (kd) of 2b11 was measured to be 5 nm using biolayer interferometry. 2b11 exhibite ...201727845043
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
immunization with lytb protein of streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis.the cell wall glucosaminidase lytb of streptococcus pneumoniae is a surface exposed protein involved in daughter cell separation, biofilm formation and contributes to different aspects of the pathogenesis process. in this study we have characterized the antibody responses after immunization of mice with lytb in the presence of alhydrogel as an adjuvant. enzyme-linked immunosorbent assays measuring different subclasses of immunoglobulin g, demonstrated that the antibody responses to lytb were pre ...201627840016
detrimental role for ccaat/enhancer binding protein δ in blood-borne brain infection.the most frequent pathogen that causes bacterial meningitis is the gram-positive bacterium streptococcus (s.) pneumoniae. ccaat/enhancer binding protein δ is a transcription factor that has recently been hypothesized to play a detrimental role in outcome of meningitis caused by s. pneumoniae. here, we studied the role of c/ebpδ prior to the development of pneumococcal meningitis.201627835970
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
announcement: world pneumonia day - november 12, 2016.november 12th marks the eighth annual world pneumonia day, observed to raise awareness of pneumonia as a global public health concern for persons of all ages and a leading infectious cause of death of children aged <5 years, causing approximately 900,000 child deaths annually (1). in the united states, the majority of the 53,000 annual pneumonia deaths occur in persons aged ≥65 years. respiratory viruses, such as respiratory syncytial virus (rsv) and influenza, and streptococcus pneumoniae bacte ...201627832057
pneumococcal serotype 5 colonization prevalence among newly arrived unaccompanied children 1 year after an outbreak-texas, 2015.in 2014, an acute respiratory illness outbreak affected unaccompanied children from central america entering the united states; 9% of 774 surveyed children were colonized with streptococcus pneumoniae serotype 5. in our 2015 follow-up survey of 475 children, serotype 5 was not detected, and an interim recommendation to administer 13-valent pneumococcal conjugate vaccine to all unaccompanied children was discontinued.201727832022
streptococcus pneumoniae serotype 19a meningitis in well-vaccinated immunocompetent 13-month-old child: a case of pcv13 failure.we report a 13-month-old immune-competent male child who was diagnosed with pneumococcal serotype 19a meningitis despite having received three pcv13 injections. clinicians are reminded that bacterial meningitis can still occur, even in correctly vaccinated children. investigations should include immune system screening along with abdominal ultrasound to exclude asplenia.201627830065
pyruvate oxidase of streptococcus pneumoniae contributes to pneumolysin release.streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. certain aspects of s. pneumoniae's virulence are dependent upon expression and release of the protein toxin pneumolysin (ply) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (spxb). we investigated the possible synergy of these two proteins and identified that release of ply is enhanced by expression of spxb prior to stationary phase growth.201627829373
pneumococcal carriage in children under five years in uganda-will present pneumococcal conjugate vaccines be appropriate?pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. pneumococcal conjugate vaccines (pcvs) are currently being implemented in many low-income countries. pcvs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. in ...201627829063
streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia.olfactory ensheathing cells (oecs) are a type of specialized glial cell currently considered as having a double function in the nervous system: one regenerative, and another immune. streptococcus pneumoniae is a major agent of severe infections in humans, including meningitis. it is commonly found in the nasopharynx of asymptomatic carriers, and, under certain still unknown conditions, can invade the brain. we evaluated whether pneumococcal cells recovered from lysed oecs and microglia are able ...201627827453
towards understanding the epidemiology of neisseria meningitidis in the african meningitis belt: a multi-disciplinary overview.neisseria meningitidis is the major cause of seasonal meningitis epidemics in the african meningitis belt. in the changing context of a reduction in incidence of serogroup a and an increase in incidence of serogroups w and c and of streptococcus pneumoniae, a better understanding of the determinants driving the disease transmission dynamics remains crucial to improving bacterial meningitis control.201727826113
comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections.necrotizing soft tissue infections (nstis) are a group of infections affecting all soft tissues. nsti involves necrosis of the afflicted tissue and is potentially life threatening due to major and rapid destruction of tissue, which often leads to septic shock and organ failure. the gold standard for identification of pathogens is culture; however molecular methods for identification of microorganisms may provide a more rapid result and may be able to identify additional microorganisms that are n ...201627821087
a semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against streptococcus pneumoniae serotype 3 infection.the identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. to investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine prevnar 13, streptococcus pneumoniae serotype 3 ...201627818299
in vivo screen of genetically conserved streptococcus pneumoniae proteins for protective immunogenicity.we evaluated 52 different e. coli expressed pneumococcal proteins as immunogens in a balb/c mouse model of s. pneumoniae lung infection. proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. three of the protective proteins were histidine triad protein family members (phtb, phtd and pht ...201627816374
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
antimicrobial activity of tachyplesin 1 against burkholderia pseudomallei: an in vitro and in silico approach.burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many conventional antibiotics. therefore, alternative antimicrobial agents such as antimicrobial peptides (amps) are extensively studied to combat this issue. our study aims to identify and understand the mode of action of the potential amp(s) that are effective against b. pseudomallei in both planktonic and biofilm state as well as to predict the possible binding targets on using in vitro and in silico ...201627812400
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
epidemiological study on the penicillin resistance of clinical streptococcus pneumoniae isolates identified as the common sequence types.there were some limitation in the current interpretation about the penicillin resistance mechanism of clinical streptococcus pneumoniae isolates at the strain level. to explore the possibilities of studying the mechanism based on the sequence types (st) of this bacteria, 488 isolates collected in beijing from 1997-2014 and 88 isolates collected in youyang county, chongqing and zhongjiang county, sichuan in 2015 were analyzed by penicillin minimum inhibitory concentration (mic) distribution and a ...201627806935
childhood acute bacterial meningitis: clinical spectrum, bacteriological profile and outcome.to determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis.201627806810
microbiologic investigation of patients before living-donor liver transplant.chronic infections can cause serious complications and create morbidity and mortality for affected patients during immunosuppressive therapy in the posttransplant period. here, we studied the microbiologic screening results of patients before living-donor liver transplant.201627805525
microbiologic monitoring of kidney transplant recipients before transplant.drug immunosuppression, traditionally used to minimize autoimmune developments after liver, kidney, heart, and lung transplant, and which requires high doses of corticosteroids, creates favorable conditions for the development of various infectious processes and the existence of pathogens, which can be activated after transplant. this study aimed to investigate the bacterial pathogens in patients before living-donor kidney transplant.201627805513
convergent evolution of the arginine deiminase pathway: the arcd and arce arginine/ornithine exchangers.the arginine deiminase (adi) pathway converts l-arginine into l-ornithine and yields 1 mol of atp per mol of l-arginine consumed. the l-arginine/l-ornithine exchanger in the pathway takes up l-arginine and excretes l-ornithine from the cytoplasm. analysis of the genomes of 1281 bacterial species revealed the presence of 124 arc gene clusters encoding the pathway. about half of the clusters contained the gene encoding the well-studied l-arginine/l-ornithine exchanger arcd, while the other half co ...201727804281
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
comparative in vivo efficacies of tedizolid in neutropenic versus immunocompetent murine streptococcus pneumoniae lung infection models.given that tedizolid exhibits substantial lung penetration, we hypothesize that it could achieve good efficacy against streptococcus pneumoniae lung infections. we evaluated the pharmacodynamics of tedizolid for treatment of s. pneumoniae lung infections and compared the efficacies of tedizolid human-simulated epithelial lining fluid (elf) exposures in immunocompetent and neutropenic murine lung infection models. icr mice were rendered neutropenic via intraperitoneal cyclophosphamide injections ...201727799200
streptococcus pneumoniae serotypes and antibiotic susceptibility patterns in middle ear fluid isolates during acute otitis media and nasopharyngeal isolates during community-acquired alveolar pneumonia in central romania.streptococcus pneumoniae is a common cause of community-acquired alveolar pneumonia (caap) and acute otitis media (aom) in children. romania has high rates of s. pneumoniae antibiotic resistance. the pneumococcal conjugated vaccines (pcvs) are not being used routinely in this country. the aims of the study were as follows: 1) to compare pneumococcal antibiotic resistance patterns in aom and caap in children from central romania and 2) to compare differences in the distribution of pneumococcal se ...201727798547
impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia.although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (capp) is lacking.201727798219
safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in china.the invasive pneumococcal diseases (ipds) caused by streptococcus pneumoniae pose an enormous threat to children under 5 years of age. however, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of ipds. the purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (pcv13) to the currently licensed 7-valent pneumococcal conjugate vaccine (pcv7).201627798013
most preschool children hospitalised for acute rhinosinusitis had orbital complications, more common in the youngest and among boys.this study established the incidence of acute rhinosinusitis and related orbital complications in tertiary care in stockholm county and surveyed the clinical outcomes.201727797408
unraveling the pore-forming steps of pneumolysin from streptococcus pneumoniae.pneumolysin (ply) is the main virulence factor of streptococcus pneumoniae that causes pneumonia, meningitis, and invasive pneumococcal infection. ply is produced as monomers, which bind to cholesterol-containing membranes, where they oligomerize into large pores. to investigate the pore-forming mechanism, we determined the crystal structure of ply at 2.4 å and used it to design mutants on the surface of monomers. electron microscopy of liposomes incubated with ply mutants revealed that several ...201627796097
management of acute complicated mastoiditis at an urban, tertiary care pediatric hospital.to describe the presentation and management of acute complicated mastoiditis in children.201627796038
infections of the central nervous system after unrelated donor umbilical cord blood transplantation or human leukocyte antigen-matched sibling transplantation.we analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (cns) infections in consecutive patients with receiving umbilical cord blood transplantation (ucbt) (n = 343) or hla-matched sibling donor stem cell transplantation (mst) (n = 366). thirty-four cns infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). the cumulative incidence (ci) risk of developing a cns infection was .6% at day +30, 2.3% at ...201727794456
comparison of culture and pcr methods in the diagnosis of bacterial meningitis.our aim in this study is to compare the standard culture method with the multiplex pcr and the speed-oligo(®) bacterial meningitis test (so-bmt) - a hybridization-based molecular test method - during the csf examination of the patients with the pre-diagnosis of acute bacterial meningitis. for the purposes of this study, patients with acute bacterial meningitis treated at the dicle university medical faculty hospital, infectious diseases and clinical microbiology clinic between december 2009 and ...201727793541
serotype 3 remains the leading cause of invasive pneumococcal disease in adults in portugal (2012-2014) despite continued reductions in other 13-valent conjugate vaccine serotypes.since 2010 the 13-valent pneumococcal conjugate vaccine (pcv13) replaced the 7-valent vaccine (pcv7) as the leading pneumococcal vaccine used in children through the private sector. although, neither of the pcvs were used significantly in adults, changes in adult invasive pneumococcal disease (ipd) were expected due to herd protection. we characterized n = 1163 isolates recovered from ipd in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobia ...201627790208
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
antibiotic resistance patterns and related mobile genetic elements of pneumococci and β-hemolytic streptococci in thai healthy children.transmission of antibiotic resistance genes among streptococcus pneumoniae and beta-hemolytic streptococcus (bhs) was generally associated with transmissible genetic elements. the objectives of this study were to investigate carriage rate, antibiotic resistance and related mobile genetic elements of pneumococci and bhs from school-children. the pneumococci and bhs were recovered from 220 thai school-children, and then tested for antibiotic susceptibility pattern by disc diffusion. antibiotic res ...201627784937
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
infectious diseases in poland in 2014the aim of the study is to assess epidemiological situation of infectious and parasitic diseases in poland in 2014, and an indication of the potential health risks from communicable diseases occurring in other areas of the globe.201727779831
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
value of polymerase chain reaction in diagnosis of streptococcus pneumoniae valve endocarditis. 201627776728
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