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population pharmacokinetic analyses for bc-3781 using phase 2 data from patients with acute bacterial skin and skin structure infections.bc-3781, a pleuromutilin antimicrobial agent, is being developed for the treatment of patients with acute bacterial skin and skin structure infections (absssi) and community-acquired bacterial pneumonia. data from a phase 2 study of patients with absssi were used to refine a previous population pharmacokinetic (pk) model and explore potential predictors of pk variability. the previously derived population pk model based on data from three phase 1 studies was applied to sparse sampling data from ...201425348519
first report on prevalence and risk factors of severe atypical pneumonia in vietnamese children aged 1-15 years.atypical pathogens such as mycoplasma pneumoniae, chlamydophila pneumoniae, and legionella pneumophila are increasingly recognized as important causes of community acquired pneumonia (cap) worldwide. such etiological data for vietnam is scarce and clinical doctors lack accurate information on which to base their diagnosis and treatment of pneumonia. this study identifies the prevalence and risk factors of severe community acquired pneumonia due to these atypical pathogens (severe-apcap) in child ...201425524126
detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia.severe pneumonia remains an important cause of morbidity and mortality. polymerase chain reaction (pcr) has been shown to be more sensitive than current standard microbiological methods--particularly in patients with prior antibiotic treatment--and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. conventional detection techniques and multiplex pcr for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory sample ...201425397673
validation of sputum gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study.the usefulness of sputum gram stain in patients with community-acquired pneumonia (cap) is controversial. there has been no study to evaluate the diagnostic value of this method in patients with healthcare-associated pneumonia (hcap). the purpose of this study was to evaluate the usefulness of sputum gram stain in etiological diagnosis and pathogen-targeted antibiotic treatment of cap and hcap.201425326650
relationship between the gold combined copd assessment staging system and bacterial isolation.acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (copd) prognosis by accelerating loss of lung function. it is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations.201425298733
the role of multiplex pcr test in identification of bacterial pathogens in lower respiratory tract infections.lower respiratory tract infection is one of the most important causes of morbidity and mortality. however establishing a microbial diagnosis for patients with lower respiratory tract infection is still challenging and is often achieved in only half of cases by conventional methods. this study was designed to compare the fast responsive pcr method with the culture method in lower respiratory tract infections and to evaluate the reliability of multiplex pcr method.201425225517
evaluation of the kinetics and mechanism of action of anti-integration host factor-mediated disruption of bacterial biofilms.the extracellular polymeric substance produced by many human pathogens during biofilm formation often contains extracellular dna (edna). strands of bacterial edna within the biofilm matrix can occur in a lattice-like network wherein a member of the dnabii family of dna-binding proteins is positioned at the vertex of each crossed strand. to date, treatment of all biofilms tested with antibodies directed against one dnabii protein, integration host factor (ihf), results in significant disruption. ...201425069521
inflammatory response in mixed viral-bacterial community-acquired pneumonia.the role of mixed pneumonia (virus+bacteria) in community-acquired pneumonia (cap) has been described in recent years. however, it is not known whether the systemic inflammatory profile is different compared to monomicrobial cap. we wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral cap.201425073709
evaluation of curetis unyvero, a multiplex pcr-based testing system, for rapid detection of bacteria and antibiotic resistance and impact of the assay on management of severe nosocomial pneumonia.health care-associated pneumonia due to multidrug-resistant organisms represents a major therapeutic challenge. unfortunately, treatment is dependent on empirical therapy, which often leads to improper and inadequate antimicrobial therapy. a rapid multiplex pcr-based unyvero pneumonia application (upa) assay that assists in timely decision-making has recently become available. in this study, we evaluated the performance of upa in detecting etiological pathogens and resistance markers in patients ...201424789196
efficacy and safety of moxifloxacin in community acquired pneumonia: a prospective, multicenter, observational study (caprivi).community acquired pneumonia (cap) is a major cause of morbidity, hospitalization, and mortality worldwide. management of cap for many patients requires rapid initiation of empirical antibiotic treatment, based on the spectrum of activity of available antimicrobial agents and evidence on local antibiotic resistance. few data exist on the severity profile and treatment of hospitalized cap patients in eastern and central europe and the middle east, in particular on use of moxifloxacin (avelox®), w ...201424975809
rapid laboratory diagnosis for respiratory infectious diseases by using maldi-tof mass spectrometry.it is still challenging to prevent and treat respiratory infectious diseases. one critical step in the successful treatment of respiratory infections is rapid diagnosis by identifying the causative microorganisms in a timely fashion. however, traditional methods for identification of causative agents could not satisfy the need for rapid and accurate testing due to the limitations of technology-used. in recent years, matrix-assisted laser desorption/ionization time of flight mass spectrometry (ma ...201424822111
the bacterial aetiology of adult community-acquired pneumonia in asia: a systematic review.community-acquired pneumonia (cap) is a major cause of adult mortality in asia. appropriate empirical treatment depends on knowledge of the pathogens commonly responsible. however, assessing the aetiological significance of identified organisms is often difficult, particularly with sputum isolates that might represent contamination with oropharyngeal flora.201424781376
viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia.viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (hap), except in patients with hematologic malignancy or transplant recipients. we investigated the role and distribution of viruses in adult with severe hap who required intensive care.201424752070
lower respiratory tract virus findings in mechanically ventilated patients with severe community-acquired pneumonia.the role of viral infections in the etiology of severe community-acquired pneumonia (scap) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit.201424729498
tools for detection of mycoplasma amphoriforme: a primary respiratory pathogen?mycoplasma amphoriforme is a recently described organism isolated from the respiratory tracts of patients with immunodeficiency and evidence of chronic infection. novel assays for the molecular detection of the organism by real-time quantitative pcrs (qpcrs) targeting the uracil dna glycosylase gene (udg) or the 23s rrna gene are described here. the analytical sensitivities are similar to the existing conventional m. amphoriforme 16s rrna gene pcr, with the advantage of being species specific, r ...201424478412
efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis and copd: a systematic review and meta-analysis.to evaluate the efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis (aecb) and chronic obstructive pulmonary disease (aecopd).201424624286
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
penetration of gsk1322322 into epithelial lining fluid and alveolar macrophages as determined by bronchoalveolar lavage.gsk1322322 is a potent peptide deformylase inhibitor with in vitro and in vivo activity against multidrug-resistant skin and respiratory pathogens. this report provides plasma and intrapulmonary pharmacokinetics, safety, and tolerability of gsk1322322 after repeat (twice daily intravenous dosing for 4 days) dosing at 1,500 mg. plasma samples were collected over the last 12-hour dosing interval of repeat dosing following the day 4 morning dose (the last dose). bronchoalveolar lavage samples were ...201424189245
real-time detection of a virus using detection dogs.viral infections are ubiquitous in humans, animals, and plants. real-time methods to identify viral infections are limited and do not exist for use in harsh or resource-constrained environments. previous research identified that tissues produce unique volatile organic compounds (voc) and demonstrated that voc concentrations change during pathologic states, including infection, neoplasia, or metabolic disease. patterns of voc expression may be pathogen specific and may be associated with an odor ...201526779494
real-time detection of a virus using detection dogs.viral infections are ubiquitous in humans, animals, and plants. real-time methods to identify viral infections are limited and do not exist for use in harsh or resource-constrained environments. previous research identified that tissues produce unique volatile organic compounds (voc) and demonstrated that voc concentrations change during pathologic states, including infection, neoplasia, or metabolic disease. patterns of voc expression may be pathogen specific and may be associated with an odor ...201526779494
polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome.microbial aetiology of intensive care unit (icu)-acquired pneumonia (icuap) determines antibiotic treatment and outcomes. the impact of polymicrobial icuap is not extensively known. we therefore investigated the characteristics and outcomes of polymicrobial aetiology of icuap.201526703094
full genomic characterization of a saffold virus isolated in peru.while studying respiratory infections of unknown etiology we detected saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. the full viral genome recovered by deep sequencing showed 98% identity to a previously described saffold strain isolated in japan. phylogenetic analysis confirmed the peruvian saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in asia. this is the first docum ...201526610576
spectrophotometric investigations of macrolide antibiotics: a brief review.macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by streptomyces species. they belong to the polyketide class of natural products. their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. they are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. different analytical techniques have been reported for the determination of macrolides such a ...201526609215
real life management of community-acquired pneumonia in adults in the gulf region and comparison with practice guidelines: a prospective study.very few data exist on the management of community-acquired pneumonia (cap) in patients admitted to hospitals in the gulf region. the objectives of this study were to describe treatment patterns for cap in 38 hospitals in five gulf countries (united arab emirates, kuwait, bahrain, oman, and qatar) and to compare the findings to the most recent infectious diseases society of america (idsa)/american thoracic society (ats) guidelines.201526424530
clinical characteristics of nursing home-acquired pneumonia in elderly patients admitted to a korean teaching hospital.nursing home-acquired pneumonia (nhap) is included under healthcare-associated pneumonia. however, the optimal treatment strategy for nhap has been controversial in several studies. we evaluated the clinical features of nhap compared to community-acquired pneumonia (cap) in elderly patients admitted with pneumonia.201526354058
differentiation of acute q fever from other infections in patients presenting to hospitals, the netherlands(1).differentiating acute q fever from infections caused by other pathogens is essential. we conducted a retrospective case-control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for q fever. patients with acute q fever were younger and had higher c-reactive protein levels but lower leukocyte coun ...201526196955
profile of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections.tedizolid phosphate is the first once-daily oxazolidinone approved by the united states food and drug administration for the treatment of acute bacterial skin and skin structure infections (absssi). it is more potent in vitro than linezolid against methicillin-resistant staphylococcus aureus (mrsa) and other gram-positive pathogens causing absssi, even retaining activity against some linezolid-resistant strains. tedizolid is approximately 90% protein bound, leading to lower free-drug concentrati ...201525960671
bacteriological assessment of healthcare-associated pneumonia using a clone library analysis.the causative pathogens of healthcare-associated pneumonia (hcap) remain controversial, and the use of conventional cultivation of sputum samples is occasionally inappropriate due to the potential for oral bacterial contamination. it is also sometimes difficult to determine whether methicillin-resistant staphylococcus aureus (mrsa) is a true causative pathogen of hcap.201525874715
the burden and etiology of community-onset pneumonia in the aging japanese population: a multicenter prospective study.the increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. this study was conducted to elucidate the burden of community-onset pneumonia (cop) and its etiologic fractions in japan, the world's most aged society.201525822890
etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in norway.despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (cap) is still not well described. we applied polymerase chain reaction (pcr) and conventional methods to describe etiology of cap in hospitalized adults and evaluated their respective diagnostic yields.201525887603
colistin for lung infection: an update.increasing incidence of resistance of gram-negative bacteria against even newer antibiotic including carbapenem has generated interest in the old antibiotic colistin, which are being used as salvage therapy in the treatment of multidrug resistant infection. colistin has excellent bactericidal activity against most gram-negative bacilli. it has shown persist level in the liver, kidney, heart, and muscle; while it is poorly distributed to the bones, cerebrospinal fluid, lung parenchyma, and pleura ...201525705428
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
the diagnostic value of serum c-reactive protein for identifying pneumonia in hospitalized patients with acute respiratory symptoms.background. the clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. in this study, we aimed to assess whether serum c-reactive protein (crp) could assist in identifying patients with pneumonia. methods. for one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. in addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of c ...201627610265
risk factors to predict drug-resistant pathogens in hemodialysis-associated pneumonia.after the concept of healthcare associated pneumonia (hcap) was introduced in 2005 by the american thoracic society/infectious disease society of america (ats/idsa), pneumonia in hemodialysis patients has been classified as hcap. even though there are several risk factors and scoring systems of drug-resistant pathogens (drps) in hcap, the risk factors for drps in hemodialysis-associated pneumonia are unclear.201627502599
canine detection of the volatilome: a review of implications for pathogen and disease detection.the volatilome is the entire set of volatile organic compounds (voc) produced by an organism. the accumulation of voc inside and outside of the body reflects the unique metabolic state of an organism. scientists are developing technologies to non-invasively detect voc for the purposes of medical diagnosis, therapeutic monitoring, disease outbreak containment, and disease prevention. detection dogs are proven to be a valuable real-time mobile detection technology for the detection of voc related ...201627446935
the fifth international meeting of isev, isev2016, rotterdam, the netherlands, 4 - 7 may, 2016. 201627247029
results from the solithromycin international surveillance program (2014).solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including streptococcus pneumoniae (1,713 isolates), haemophilus influenzae (1,308), moraxella catarrhalis (577), staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. the geographic s ...201627044551
derivation and multicenter validation of the drug resistance in pneumonia clinical prediction score.the health care-associated pneumonia (hcap) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. we aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of hcap criteria. a derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. ris ...201626856838
facility characteristics as independent prognostic factors of nursing home-acquired pneumonia.recently, the incidence of nursing home-acquired pneumonia (nhap) has been increasing and is now the leading cause of death among nursing home residents. this study was performed to identify risk factors associated with nhap mortality, focusing on facility characteristics.201626837007
comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia.the frequent lack of a microbiological diagnosis in community-acquired pneumonia (cap) impairs pathogen-directed antimicrobial therapy. this study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with cap.201626747825
correlation between acrb trimer association affinity and efflux activity.the majority of membrane proteins function as oligomers. however, it remains largely unclear how the oligomer stability of protein complexes correlates with their function. understanding the relationship between oligomer stability and activity is essential to protein research and to virtually all cellular processes that depend on the function of protein complexes. proteins make lasting or transient interactions as they perform their functions. obligate oligomeric proteins exist and function excl ...201424854514
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
in vitro antimicrobial activity of doripenem, a new carbapenem.the doripenem mics at which 90% of the tested strains were inhibited ranged from 0.03 to 1 microg/ml for 10 species of enterobacteriaceae (n = 351), from 0.03 to 0.12 microg/ml for oxacillin-susceptible staphylococci (n = 119), from 4 to 32 microg/ml for oxacillin-resistant staphylococci (n = 64), from < or =0.008 to 0.06 microg/ml for penicillin-susceptible streptococci (n = 132), and from 1 to 4 microg/ml for penicillin-resistant streptococci (n = 51). overall, doripenem demonstrated in vitro ...200415047550
antimicrobial activity and spectrum of ppi-0903m (t-91825), a novel cephalosporin, tested against a worldwide collection of clinical strains.ppi-0903m is a novel n-phosphono-type cephalosporin active against oxacillin-resistant staphylococci and many other gram-positive organisms. this study evaluated the in vitro activity and spectrum of ppi-0903m against 1,478 recent clinical isolates collected from 80 medical centers (22 countries). ppi-0903m demonstrated broader in vitro activity against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci of current clinical concern, than currently avai ...200516048970
in vitro and in vivo antibacterial activities of dw-224a, a new fluoronaphthyridone.dw-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. against gram-negative bacteria, dw-224a was slightly less active than the other fluoroquinolones. the in vivo activities of dw-224a against gram-positive bacteria were more potent than those of other quinolones.200616723601
tigecycline: an evidence-based review of its antibacterial activity and effectiveness in complicated skin and soft tissue and intraabdominal infections.there is an urgent need for novel agents to manage serious bacterial infections, particularly those contracted in healthcare facilities. tigecycline is a novel broad-spectrum glycylcycline with good activity against gram-positive, many gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need.200622500153
evaluation of the merlin micronaut system for rapid direct susceptibility testing of gram-positive cocci and gram-negative bacilli from positive blood cultures.bloodstream infections are life-threatening conditions which require the timely initiation of appropriate antimicrobial therapy. we evaluated the automated merlin micronaut system for rapid direct microtiter broth antimicrobial susceptibility testing (ast) of gram-positive cocci and gram-negative bacilli from bactec 9240 bottles with positive blood cultures in comparison to the standard method for the merlin micronaut system. this prospective study was conducted under routine working conditions ...200717202283
nosocomial pneumonia in critically ill patients.the care of critically ill patients in the intensive care unit (icu) is a primary component of modern medicine. icus create potential for recovery in patients who otherwise may not have survived. however, they may suffer from problems associated with of nosocomial infections. nosocomial infections are those which manifest in patients 48 hours after admission to hospital. nosocomial infections are directly related to diagnostic, interventional or therapeutic procedures a patient undergoes in hosp ...201020931034
activity of the thiopeptide antibiotic nosiheptide against contemporary strains of methicillin-resistant staphylococcus aureus.the rapid rise in antimicrobial resistance in bacteria has generated an increased demand for the development of novel therapies to treat contemporary infections, especially those caused by methicillin-resistant staphylococcus aureus (mrsa). however, antimicrobial development has been largely abandoned by the pharmaceutical industry. we recently isolated the previously described thiopeptide antibiotic nosiheptide from a marine actinomycete strain and evaluated its activity against contemporary cl ...201223047246
repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative.febrile neutropenia is a common reason for the hospitalization of pediatric oncology patients. the initiation of antibiotics and the overall decline in rates of bacteremia, would predict a low yield of detection of bacteremia in repeated blood cultures. despite little evidence supporting the utility of serial cultures, repeat culturing with fever persists.201223047811
repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative.febrile neutropenia is a common reason for the hospitalization of pediatric oncology patients. the initiation of antibiotics and the overall decline in rates of bacteremia, would predict a low yield of detection of bacteremia in repeated blood cultures. despite little evidence supporting the utility of serial cultures, repeat culturing with fever persists.201223047811
the human milk protein-lipid complex hamlet sensitizes bacterial pathogens to traditional antimicrobial agents.the fight against antibiotic resistance is one of the most significant challenges to public health of our time. the inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. one such compound is hamlet, a natural complex from human milk that kills streptococcus pneumoniae (the pneumococcus) using a mechanism ...201222905269
identification of ata, a multifunctional trimeric autotransporter of acinetobacter baumannii.acinetobacter baumannii has recently emerged as a highly troublesome nosocomial pathogen, especially in patients in intensive care units and in those undergoing mechanical ventilation. we have identified a surface protein adhesin of a. baumannii, designated the acinetobacter trimeric autotransporter (ata), that contains all of the typical features of trimeric autotransporters (ta), including a long signal peptide followed by an n-terminal, surface-exposed passenger domain and a c-terminal domain ...201222609912
proteomic analysis of neisseria gonorrhoeae biofilms shows shift to anaerobic respiration and changes in nutrient transport and outermembrane proteins.neisseria gonorrhoeae, the causative agent of gonorrhea, can form biofilms in vitro and in vivo. in biofilms, the organism is more resistant to antibiotic treatment and can serve as a reservoir for chronic infection. we have used stable isotope labeling by amino acids in cell culture (silac) to compare protein expression in biofilm and planktonic organisms. two parallel populations of n. gonorrhoeae strain 1291, which is an arginine auxotroph, were grown for 48 h in continuous-flow chambers over ...201222701624
current epidemiology and growing resistance of gram-negative pathogens.in the 1980s, gram-negative pathogens appeared to have been beaten by oxyimino-cephalosporins, carbapenems, and fluoroquinolones. yet these pathogens have fought back, aided by their membrane organization, which promotes the exclusion and efflux of antibiotics, and by a remarkable propensity to recruit, transfer, and modify the expression of resistance genes, including those for extended-spectrum β-lactamases (esbls), carbapenemases, aminoglycoside-blocking 16s rrna methylases, and even a quinol ...201222707882
quantitative real-time pcr for detection of acinetobacter baumannii colonization in the hospital environment.a real-time pcr assay was developed for detecting the presence of acinetobacter baumannii on hospital equipment and compared to conventional bacterial culture using 100 hospital environmental samples. the real-time pcr detected contaminated surfaces in 4 h with high sensitivity (100%) compared to conventional culture. thirty-eight percent of samples were positive by real-time pcr and negative by bacterial culture (false positives), possibly indicating the widespread presence of bacterial dna tha ...201222301021
a new pharmacological agent (akb-4924) stabilizes hypoxia inducible factor-1 (hif-1) and increases skin innate defenses against bacterial infection.hypoxia inducible factor-1 (hif-1) is a transcription factor that is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress. hif-1 is also activated in response to bacterial pathogens and supports the innate immune response of both phagocytes and keratinocytes. in this work, we show that a new pharmacological compound akb-4924 increases hif-1 levels and enhances the antibacterial activity of phagocytes and keratinocytes against both methicillin-sensitive and methici ...201222371073
dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics.the judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise toxicity. critical to dose optimisation is an understanding of the pharmacokinetics and pharmacodynamics of available drugs. optimal dosing strategies may take advantage of pharmacokinetic/pharmacodynamic (pk/pd) principles so that antibiotic dosing can be individualised to assure effective bacterial killing in patients who have a ...201324389079
dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics.the judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise toxicity. critical to dose optimisation is an understanding of the pharmacokinetics and pharmacodynamics of available drugs. optimal dosing strategies may take advantage of pharmacokinetic/pharmacodynamic (pk/pd) principles so that antibiotic dosing can be individualised to assure effective bacterial killing in patients who have a ...201324389079
in vitro activity of ceftaroline-avibactam against gram-negative and gram-positive pathogens isolated from patients in canadian hospitals from 2010 to 2012: results from the canward surveillance study.the in vitro activities of ceftaroline-avibactam, ceftaroline, and comparative agents were determined for a collection of bacterial pathogens frequently isolated from patients seeking care at 15 canadian hospitals from january 2010 to december 2012. in total, 9,758 isolates were tested by using the clinical and laboratory standards institute (clsi) broth microdilution method (document m07-a9, 2012), with mics interpreted by using clsi breakpoints (document m100-s23, 2013). ceftaroline-avibactam ...201323979759
on the essentiality of lipopolysaccharide to gram-negative bacteria.lipopolysaccharide is a highly acylated saccharolipid located on the outer leaflet of the outer membrane of gram-negative bacteria. lipopolysaccharide is critical to maintaining the barrier function preventing the passive diffusion of hydrophobic solutes such as antibiotics and detergents into the cell. lipopolysaccharide has been considered an essential component for outer membrane biogenesis and cell viability based on pioneering studies in the model gram-negative organisms escherichia coli an ...201324148302
structure-based gene targeting discovery of sphaerimicin, a bacterial translocase i inhibitor.rise and shine: using a gene-targeting approach aimed at identifying potential l-threonine:uridine-5'-transaldolases that catalyze the formation of (5's,6's)-c-glycyluridine, a new bacterial translocase i inhibitor was discovered from an actinomycete following fermentation optimization.201324014169
efficacy of levofloxacin versus cefuroxime in treating acute exacerbations of chronic obstructive pulmonary disease.antibiotic treatment is one of the major pharmacologic treatments for acute exacerbation of chronic obstructive pulmonary disease (aecopd). however, the choice of antibiotic depends on the local resistance pattern. a multicenter, randomized, controlled trial was done in patients with aecopd to compare the efficacy of levofloxacin with that of cefuroxime axetil.201323874094
rna-seq-based analysis of the physiologic cold shock-induced changes in moraxella catarrhalis gene expression.moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. the prevalence of pharyngeal colonization and respiratory tract infections caused by m. catarrhalis is greatest in winter. we investigated how m. catarrhalis uses the physiologic exposure to cold air to regulate pivotal survival systems that may contribute to m. catarrhalis virulence.201323844181
antianaerobic antimicrobials: spectrum and susceptibility testing.susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. the clinical and laboratory standards institute (clsi) has standardized many laboratory procedures, including anaerobic susceptibility testing (ast), and has published documents for ast. the standardization of testing methods by the clsi allows comparisons of resistance trends among various laboratories. susceptibility testing should be performed on organisms recovered fr ...201323824372
bronchoscopy-derived correlates of lung injury following inhalational injuries: a prospective observational study.acute lung injury (ali) is a major factor determining morbidity following burns and inhalational injury. in experimental models, factors potentially contributing to ali risk include inhalation of toxins directly causing cell damage; inflammation; and infection. however, few studies have been done in humans.201323691180
sensitization of staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of hamlet.hamlet (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. hamlet exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including staphylococci. still, ion transport associated with death in s. pneumoniae is also detected to a lower degree in insensitive organi ...201323650551
rapid discrimination of haemophilus influenzae, h. parainfluenzae, and h. haemolyticus by fluorescence in situ hybridization (fish) and two matrix-assisted laser-desorption-ionization time-of-flight mass spectrometry (maldi-tof-ms) platforms.due to considerable differences in pathogenicity, haemophilus influenzae, h. parainfluenzae and h. haemolyticus have to be reliably discriminated in routine diagnostics. retrospective analyses suggest frequent misidentifications of commensal h. haemolyticus as h. influenzae. in a multi-center approach, we assessed the suitability of fluorescence in situ hybridization (fish) and matrix-assisted laser-desorption-ionization time-of-flight mass-spectrometry (maldi-tof-ms) for the identification of h ...201323646201
applications of pharmacometrics in the clinical development and pharmacotherapy of anti-infectives.with the increased emergence of anti-infective resistance in recent years, much focus has recently been drawn to the development of new anti-infectives and the optimization of treatment regimens and combination therapies for established antimicrobials. in this context, the field of pharmacometrics using quantitative numerical modeling and simulation techniques has in recent years emerged as an invaluable tool in the pharmaceutical industry, academia and regulatory agencies to facilitate the inte ...201323473593
rapid identification of bacteria and yeasts from positive-blood-culture bottles by using a lysis-filtration method and matrix-assisted laser desorption ionization-time of flight mass spectrum analysis with the saramis database.rapid identification of microorganisms causing bloodstream infections directly from a positive blood culture would decrease the time to directed antimicrobial therapy and greatly improve patient care. matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry (ms) is a fast and reliable method for identifying microorganisms from positive culture. this study evaluates the performance of a novel filtration-based method for processing positive-blood-culture broth for i ...201323254131
lipopolysaccharide-deficient acinetobacter baumannii shows altered signaling through host toll-like receptors and increased susceptibility to the host antimicrobial peptide ll-37.infections caused by multidrug-resistant acinetobacter baumannii have emerged as a serious global health problem. we have shown previously that a. baumannii can become resistant to the last-line antibiotic colistin via the loss of lipopolysaccharide (lps), including the lipid a anchor, from the outer membrane (j. h. moffatt, m. harper, p. harrison, j. d. hale, e. vinogradov, t. seemann, r. henry, b. crane, f. st. michael, a. d. cox, b. adler, r. l. nation, j. li, and j. d. boyce, antimicrob. age ...201323250952
influenza a(h1n1)pdm09-associated pneumonia deaths in thailand.the first human infections with influenza a(h1n1)pdm09 virus were confirmed in april 2009. we describe the clinical and epidemiological characteristics of influenza a(h1n1)pdm09-associated pneumonia deaths in thailand from may 2009-january 2010.201323390508
lower respiratory tract infections (ltris): an insight into the prevalence and the antibiogram of the gram negative, respiratory, bacterial agents.community acquired respiratory tract infections are one of the commonest health issues globally, which demand frequent visits to the family practitioners. the emergence of antibiotic resistance in the frequently isolated pathogens has complicated the use of the empiric therapy with traditional agents.201323543819
the negatively charged regions of lactoferrin binding protein b, an adaptation against anti-microbial peptides.lactoferrin binding protein b (lbpb) is a bi-lobed membrane bound lipoprotein that is part of the lactoferrin receptor complex in a variety of gram-negative pathogens. despite high sequence diversity among lbpbs from various strains and species, a cluster of negatively charged amino acids is invariably present in the protein's c-terminal lobe in all species except moraxella bovis. the function of lbpb in iron acquisition has yet to be experimentally demonstrated, whereas in vitro studies have sh ...201424465982
the skin microbiome in healthy and allergic dogs.changes in the microbial populations on the skin of animals have traditionally been evaluated using conventional microbiology techniques. the sequencing of bacterial 16s rrna genes has revealed that the human skin is inhabited by a highly diverse and variable microbiome that had previously not been demonstrated by culture-based methods. the goals of this study were to describe the microbiome inhabiting different areas of the canine skin, and to compare the skin microbiome of healthy and allergic ...201424421875
kingella kingae: carriage, transmission, and disease.kingella kingae is a common etiology of pediatric bacteremia and the leading agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. this gram-negative bacterium is carried asymptomatically in the oropharynx and disseminates by close interpersonal contact. the colonized epithelium is the source of bloodstream invasion and dissemination to distant sites, and certain clones show significant association with bacteremia, osteoarthritis, or endocarditis. kingella kingae produces ...201525567222
two outer membrane proteins are bovine lactoferrin-binding proteins in mannheimia haemolytica a1.mannheimia haemolytica is a gram negative bacterium that is part of the bovine respiratory disease, which causes important economic losses in the livestock industry. in the present work, the interaction between m. haemolytica a1 and bovine lactoferrin (blf) was studied. this iron-chelating glycoprotein is part of the mammalian innate-immune system and is present in milk and mucosal secretions; lf is also contained in neutrophils secondary granules, which release this glycoprotein at infection si ...201627599994
types and drug susceptibility patterns of bacterial isolates from eye discharge samples at gondar university hospital, northwest ethiopia.the type and pattern of organisms that cause ocular infection changes over time. moreover, the causative organisms have developed increased drug resistance. therefore, the aim of this study was to determine the prevalent bacterial agents of eye discharge and their drug susceptibility patterns to commonly used antimicrobial agents.201424885599
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
draft genome sequence of psychrobacter sp. ennn9_iii, a strain isolated from water in a polluted temperate estuarine system (ria de aveiro, portugal).the genus psychrobacter includes gram-negative coccobacilli that are non-pigmented, oxidase-positive, non-motile, psychrophilic or psychrotolerant, and halotolerant. psychrobacter strain ennn9_iii was isolated from water in a polluted temperate estuarine system, contaminated with hydrocarbons and heavy metals. the genome has a g + c content of 42.7%, 2618 open reading frames (orfs), three copies of the rrnas operon, and 29 trna genes. twenty-five sequences related to the degradation of aromatic ...201627114904
effects of vaccination with 10-valent pneumococcal non-typeable haemophilus influenza protein d conjugate vaccine (phid-cv) on the nasopharyngeal microbiome of kenyan toddlers.pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable haemophilus influenzae protein-d conjugate vaccine (phid-cv).201526083474
the microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx.invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. this poses substantial challenges to longitudinal study of paediatric airway microbiota. non-invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. in this study, we compared the upper and lower airway microbiota in you ...201627388563
nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis.upper respiratory infections (uri) and their complications are a major healthcare burden for pediatric populations. although the microbiology of the nasopharynx is an important determinant of the complications of uri, little is known of the nasopharyngeal (np) microbiota of children, the factors that affect its composition, and its precise relationship with uri.201627364497
accumulation of trospectomycin by strains of salmonella typhimurium, escherichia coli and haemophilus influenzae.trospectomycin, unlike aminoglycosidic aminocyclitols, is accumulated by a nonsaturable, energy-independent, diffusional process in salmonella typhimurium, escherichia coli and haemophilus influenzae. a deep rough mutant of s typhimurium was more susceptible and accumulated the drug faster, and f porin deficient mutants of e coli were more resistant than parental strains. trospectomycin likely uses both porin and nonporin pathways to cross the outer membrane. an e coli strain effectively accumul ...199022553440
clinical features fail to distinguish respiratory infections caused by branhamella catarrhalis from those caused by haemophilus influenzae.branhamella catarrhalis is being isolated with increasing frequency from patients with symptoms and signs of respiratory tract infection. records of 77 patients were reviewed to define the spectrum of respiratory illness and to compare clinical and laboratory features with those of respiratory infection due to haemophilus influenzae. both b catarrhalis and h influenzae caused respiratory infection predominantly in elderly males with underlying heart or lung disease. there were no clinical or lab ...199222451757
cefixime use in children: when and why. 199522514398
epidemiological typing of moraxella catarrhalis by pulsed field gel electrophoresis.pulsed field gel electrophoresis (pfge) was used to compare 59 strains of moraxella catarrhalis to evaluate pfge for the epidemiological typing of this organism. pfge-generated patterns were compared with those obtained by small fragment restriction enzyme analysis (rea) and species-specific probe hybridization. the strains used in the study were isolated from various geographic locations and included proven epidemiologically related strains. pfge yielded more unique patterns than dna-dna hybrid ...199522514386
recent advances: medical microbiology. 19989774296
are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? a meta-analysis.to examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors.19989727991
treatment of the common cold. 19989651268
re: the new macrolide antibiotics: use them carefully. 199820401263
antibiotic management of acute otitis media. 199820401260
acute otitis media. 199910496831
pharmacokinetics and inflammatory-fluid penetration of moxifloxacin following oral or intravenous administration.a single 400-mg oral or intravenous (i.v.) dose of moxifloxacin was given to each of eight healthy male volunteers, and 6 weeks later the dose was administered by the other route. the concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured over the subsequent 24 h. the mean maximum concentrations observed in plasma were 4.98 microg/ml after oral dosing and 5.09 microg/ml after i.v. dosing. the mean maximum concentrations attained in the inflammatory ...199910348784
a cross-canada surveillance of antimicrobial resistance in respiratory tract pathogens.to determine the prevalence of antimicrobial resistance in clinical isolates of streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis from medical centres across canada.199922346378
interpretation of middle ear fluid concentrations of antibiotics: comparison between ceftibuten, cefixime and azithromycin.the aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media.199910215750
eye disorders: bacterial conjunctivitis. 200010986192
determination of mic quality control ranges for abt-733, a novel ketolide antimicrobial agent. quality control study group. 200010917777
selective iga deficiency (sigad) and common variable immunodeficiency (cvid). 200010792368
the pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing.to examine the pharmacokinetics of ciprofloxacin and fleroxacin in plasma and sputum of patients with an acute exacerbation of chronic bronchitis or bronchiectasis following the first dose and again during the third day of treatment.200010606835
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