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1.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(1): 55-56, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30342825

RESUMO

INTRODUCTION: Burkholderia gladioli are non-fermenting, Gram-negative, rod-shaped aerobic bacteria that were first identified as a plant pathogen. Most of the B. gladioli infections reported in the literature have involved immunocompromised adults and newborn infants. B. gladioli in humans is often associated with a poor prognosis. CASE REPORT: We describe the first case of sinonasal infection due to B. gladioli and Staphylococcus aureus in an immunocompetent patient who had recently travelled to the Congo. DISCUSSION: As in the few other reported cases involving immunocompetent patients, the appropriate approach to this multidrug-resistant B. gladioli infection was a combination of surgery and antibiotics chosen in the light of an antibiogram.


Assuntos
Infecções por Burkholderia/diagnóstico , Sinusite Maxilar/microbiologia , Rinite/microbiologia , Doença Relacionada a Viagens , Antibacterianos/uso terapêutico , Infecções por Burkholderia/terapia , Burkholderia gladioli , Endoscopia , Feminino , Humanos , Imunocompetência , Levofloxacino/uso terapêutico , Sinusite Maxilar/terapia , Pessoa de Meia-Idade , Rinite/terapia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/terapia
2.
ACS Infect Dis ; 4(5): 806-814, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29461800

RESUMO

The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development necessitates novel therapeutics. Peptide-conjugated phosphorodiamidate morpholino oligomers are antisense molecules that inhibit bacterial mRNA translation. Targeting of PPMOs to the gene acpP, which is essential for membrane synthesis, lead to defects in the membrane and ultimately bactericidal activity. Exploration of additional PPMO sequences identified the ATG and Shine-Dalgarno sites as the most efficacious for targeting acpP. The CF lung is a complex microenvironment, but PPMO inhibition was still efficacious in an artificial model of CF sputum. PPMOs had low toxicity in human CF cells at doses that were antibacterial. PPMOs also reduced the bacterial burden in the lungs of immunocompromised CyBB mice, a model of CGD. Finally, the use of multiple PPMOs was efficacious in inhibiting the growth of both Burkholderia and Pseudomonas in an in vitro model of coinfection. Due to the intrinsic resistance of Burkholderia to traditional antibiotics, PPMOs represent a novel and viable approach to the treatment of Burkholderia infections.


Assuntos
Infecções por Burkholderia/microbiologia , Burkholderia/genética , Oligonucleotídeos Antissenso/genética , Pneumonia Bacteriana/microbiologia , Animais , Antibacterianos/administração & dosagem , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/genética , Fibrose Cística/complicações , Modelos Animais de Doenças , Camundongos , Testes de Sensibilidade Microbiana , Morfolinos/administração & dosagem , Morfolinos/química , Morfolinos/genética , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/química , Pneumonia Bacteriana/terapia
3.
Wien Klin Wochenschr ; 129(15-16): 527-532, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28236043

RESUMO

Registry data for patients with cystic fibrosis (CF) are increasingly used to evaluate the natural history, for benchmarking of therapy and in order to identify eligible patients for clinical studies. So far, no data on frequency and clinical status of CF patients have been available for Austria on a national level. We collected data of CF patients treated 2014 in Austrian CF outpatient clinics by means of a European CF registry and on an individual search basis. A total of 773 CF patients with a median age of 18.9 years (SD 11.8 years) were seen in 13 centers (18-151 patients/center). Homozygous F508del mutation being the most common genotype was observed in 48.8% of patients. Mean age at diagnosis was 27 days. In 59% of all patients FEV1% predicted (Forced Exspiratory Volume in 1 second) was <80% and in 20% <50%. An average FEV1 predicted decline per year of 1.9% was observed between 6-18 years of age. Colonisation with Pseudomonas aeruginosa ranged between 12% and 69% in adult patients and in 0-16% in children with CF. Burkholderia cepacia complex species were present in a total of 29 samples (3.8%). Insulin therapy for diabetes was given in 14.5%. Liver involvement was reported in 36.3%. A wide variation of prescribed CF therapy was observed between centers. Data on CF patients living in Austria are now available and form a basis for clinical benchmarking as well as analyses from a public health perspective.


Assuntos
Fibrose Cística , Adolescente , Adulto , Áustria/epidemiologia , Infecções por Burkholderia/complicações , Infecções por Burkholderia/epidemiologia , Infecções por Burkholderia/terapia , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Fibrose Cística/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Progressão da Doença , Feminino , Seguimentos , Volume Expiratório Forçado , Genótipo , Humanos , Lactente , Masculino , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/terapia , Sistema de Registros , Adulto Jovem
4.
J Med Toxicol ; 13(2): 173-179, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28105575

RESUMO

INTRODUCTION: Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. METHODS: We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. CONCLUSIONS: Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.


Assuntos
Ácido Bongcréquico/envenenamento , Infecções por Burkholderia/microbiologia , Burkholderia gladioli/metabolismo , Cocos/microbiologia , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/microbiologia , Mitocôndrias/enzimologia , Translocases Mitocondriais de ADP e ATP/antagonistas & inibidores , Zea mays/microbiologia , Animais , Ácido Bongcréquico/farmacocinética , Infecções por Burkholderia/enzimologia , Infecções por Burkholderia/epidemiologia , Infecções por Burkholderia/terapia , Burkholderia gladioli/patogenicidade , Doenças Transmitidas por Alimentos/enzimologia , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/terapia , Mitocôndrias/patologia , Translocases Mitocondriais de ADP e ATP/metabolismo , Resultado do Tratamento
5.
Perit Dial Int ; 36(4): 390-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26493755

RESUMO

UNLABELLED: ♦ BACKGROUND: Burkholderia cepacia is a hardy bacterium with intrinsic resistance to multiple antibiotics and high transmissibility. Opportunistic healthcare-associated B. cepacia infections among immunocompromised or critically ill patients have been reported, but there is limited data on the clinical characteristics and treatment outcomes of exit-site infection (ESI) in peritoneal dialysis (PD) patients. ♦ PATIENTS AND METHODS: Patients who suffered from B. cepacia ESI from 1 January 2004 to 31 December 2014 were reviewed. The clinical characteristics and treatment outcomes of the patients and the antibiotic susceptibility patterns of the bacterial isolates were analyzed. ♦ RESULTS: Twenty-two patients were included for analysis. Eight patients (36.4%) had medical conditions which impaired host immunity, while 7 (31.8%) had pre-existing skin abnormalities. Three patients (13.6%) progressed to tunnel-tract infection and another 3 patients (13.6%) developed associated peritonitis. Fifteen patients (68.2%) responded to medical treatment while 7 (31.8%) required catheter removal. Eleven patients (50.0%) had recurrent B. cepacia ESI, which occurred at 7.8 months (95% confidence interval [CI] 0.1 - 19.4 months) after the first episode. Most B. cepacia strains were susceptible to ceftazidime (95.5%), piperacillin/tazobactam (95.5%), and piperacillin (90.9%). Besides aminoglycosides (80 - 100%), high rates of resistance were also observed for ticarcillin/clavulanate (90.9%). ♦ CONCLUSION: Burkholderia cepacia ESI is associated with low rates of tunnel-tract infection or peritonitis, but the risk of recurrence is high. Most cases can be managed with medical treatment alone, although one third of patients might require catheter removal.


Assuntos
Infecções por Burkholderia/diagnóstico , Infecções por Burkholderia/etiologia , Burkholderia cepacia , Infecções Relacionadas a Cateter/etiologia , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Idoso , Antibacterianos/uso terapêutico , Infecções por Burkholderia/terapia , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/terapia , Cateteres de Demora/efeitos adversos , Remoção de Dispositivo , Farmacorresistência Bacteriana , Feminino , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Peritonite/diagnóstico , Peritonite/microbiologia , Peritonite/terapia , Estudos Retrospectivos , Resultado do Tratamento
6.
Antimicrob Agents Chemother ; 58(7): 4005-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24798268

RESUMO

Phage therapy has been suggested as a potential treatment for highly antibiotic-resistant bacteria, such as the species of the Burkholderia cepacia complex (BCC). To address this hypothesis, experimental B. cenocepacia respiratory infections were established in mice using a nebulizer and a nose-only inhalation device. Following infection, the mice were treated with one of five B. cenocepacia-specific phages delivered as either an aerosol or intraperitoneal injection. The bacterial and phage titers within the lungs were assayed 2 days after treatment, and mice that received the aerosolized phage therapy demonstrated significant decreases in bacterial loads. Differences in phage activity were observed in vivo. Mice that received phage treatment by intraperitoneal injection did not demonstrate significantly reduced bacterial loads, although phage particles were isolated from their lung tissue. Based on these data, aerosol phage therapy appears to be an effective method for treating highly antibiotic-resistant bacterial respiratory infections, including those caused by BCC bacteria.


Assuntos
Bacteriófagos , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia , Infecções Respiratórias/terapia , Aerossóis , Animais , Carga Bacteriana , Farmacorresistência Bacteriana , Feminino , Hospedeiro Imunocomprometido , Injeções Intraperitoneais , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Myoviridae , Resultado do Tratamento
7.
Tuberk Toraks ; 60(1): 52-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22554367

RESUMO

Congenital isolated pleural effusion, a non-specific accumulation of fluid in the pleural space, is an uncommon anomaly which can be associated with structural malformations, inflammatory or iatrogenic problems, genetic syndromes or fetal hydrops. Here, we present two neonates with isolated congenital pleural effusion, one of which was associated with Down syndrome and the other with empyema and bloodstream infection caused by Burkholderia gladioli septicemia. We wanted to discuss the diagnosis and management of this rare clinical entity.


Assuntos
Infecções por Burkholderia/complicações , Burkholderia gladioli/isolamento & purificação , Síndrome de Down/complicações , Derrame Pleural/congênito , Derrame Pleural/diagnóstico , Antibacterianos/uso terapêutico , Infecções por Burkholderia/diagnóstico , Infecções por Burkholderia/terapia , Síndrome de Down/diagnóstico , Drenagem , Feminino , Humanos , Recém-Nascido , Masculino , Derrame Pleural/etiologia , Derrame Pleural/terapia , Resultado do Tratamento
8.
J Hosp Infect ; 81(2): 104-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22579442

RESUMO

BACKGROUND: There is currently little evidence regarding potential risks of bacterial contamination of non-invasive ventilation (NIV) devices used by cystic fibrosis (CF) patients. AIM: The aim of this study was to determine the extent of bacterial contamination of NIV devices in our regional adult CF centre. METHODS: Seven NIV devices recently used by CF patients chronically infected with Pseudomonas aeruginosa or Burkholderia cepacia complex (BCC) were swabbed in seven areas, both external and internal. Two devices had undergone ethylene oxide (EtO) sterilization between patient use and swabbing, and five devices had not undergone EtO sterilization. FINDINGS: Swabs from five devices had insignificant growth of environmental organisms and two devices had significant growth of environmental organisms. No CF pathogens were isolated from any machine. CONCLUSIONS: No evidence was found of pathogenic microbial contamination of NIV devices used by CF patients in this small study. We suggest that further studies examine for evidence of bacterial contamination of NIV devices and that this issue should be included in future CF infection control guidelines.


Assuntos
Bactérias/isolamento & purificação , Infecções por Burkholderia/terapia , Fibrose Cística/complicações , Fibrose Cística/terapia , Infecções por Pseudomonas/terapia , Ventiladores Mecânicos/microbiologia , Adulto , Humanos
9.
Mikrobiyol Bul ; 46(2): 304-18, 2012 Apr.
Artigo em Turco | MEDLINE | ID: mdl-22639321

RESUMO

Burkholderia cepacia complex is a group of 17 closely related species. For a long time B.cepacia complex is believed to be only a plant pathogen but later it has emerged as an important opportunistic pathogen causing morbidity and mortality in hospitalized patients. B.cepacia complex particularly causes bacteraemia/sepsis, septic arthritis, osteomyelitis, meningitis, peritonitis, urinary and respiratory tract infections. Patients with cystic fibrosis or chronic granulomatous disease are predisposed to B.cepacia complex infections. B.cepacia complex can survive for a long period of time and can easily multiply in aqueous environments such as disinfectant agents and intravenous fluids used in hospitals. Patients may acquire B.cepacia complex either from the environment or through patient-to-patient transmission. It has always been a tedious task for routine microbiology laboratory to identify B.cepacia complex. In these laboratories, the identification of B.cepacia complex isolates is generally performed using a combination of selective media, conventional biochemical analysis and/or commercial systems. Three media commonly used for isolation of B.cepacia complex are as follows: the Pseudomonas cepacia agar, the oxidation-fermentation based polymyxin bacitracin lactose agar, and more recently the B.cepacia selective agar. Members of the B.cepacia complex can be identified by available commercial tests, such as API 20NE, Phoenix, MicroScan or VITEK. Molecular techniques are useful for confirmation of phenotypic identification and discrimination beyond the species-level. B.cepacia complex is intrinsically resistant to antimicrobial agents such as aminoglycosides, first- and second-generation cephalosporins, antipseudomonal penicillins and polymyxins. B.cepacia complex bacteria often develop resistance to beta-lactams due to presence of inducible chromosomal beta-lactamases and altered penicillin- binding proteins. Antibiotic efflux pumps in B.cepacia complex bacteria mediate resistance to chloramphenicol, trimethoprim and fluoroquinolones. Under antimicrobial pressure, resistance can quickly develop to all susceptible antimicrobials. In this review, the classification and microbiological features of B.cepacia complex, mechanisms of virulence and pathogenesis, epidemiological properties, clinical spectrum, laboratory diagnosis, antimicrobial resistance and treatment, prevention and control measures were summarized.


Assuntos
Infecções por Burkholderia/microbiologia , Complexo Burkholderia cepacia/patogenicidade , Hospedeiro Imunocomprometido , Infecções Oportunistas/microbiologia , Infecções por Burkholderia/complicações , Infecções por Burkholderia/diagnóstico , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/classificação , Complexo Burkholderia cepacia/efeitos dos fármacos , Complexo Burkholderia cepacia/isolamento & purificação , Fibrose Cística/complicações , Fibrose Cística/imunologia , Farmacorresistência Bacteriana Múltipla , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/imunologia , Humanos , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/terapia , Virulência , Resistência beta-Lactâmica
10.
J Infect Dis ; 205(11): 1709-18, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22448004

RESUMO

BACKGROUND: New therapeutic targets for antibiotic-resistant bacterial pathogens are desperately needed. The bacterial surface polysaccharide poly-ß-(1-6)-N-acetyl-glucosamine (PNAG) mediates biofilm formation by some bacterial species, and antibodies to PNAG can confer protective immunity. By analyzing sequenced genomes, we found that potentially multidrug-resistant bacterial species such as Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia, and the Burkholderia cepacia complex (BCC) may be able to produce PNAG. Among patients with cystic fibrosis patients, highly antibiotic-resistant bacteria in the BCC have emerged as problematic pathogens, providing an impetus to study the potential of PNAG to be targeted for immunotherapy against pan-resistant bacterial pathogens. METHODS: The presence of PNAG on BCC was assessed using a combination of bacterial genetics, microscopy, and immunochemical approaches. Antibodies to PNAG were tested using opsonophagocytic assays and for protective efficacy against lethal peritonitis in mice. RESULTS: PNAG is expressed in vitro and in vivo by the BCC, and cystic fibrosis patients infected by the BCC species B. dolosa mounted a PNAG-specific opsonophagocytic antibody response. Antisera to PNAG mediated opsonophagocytic killing of BCC and were protective against lethal BCC peritonitis even during coinfection with methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Our findings raise potential new therapeutic options against PNAG-producing bacteria, including even pan-resistant pathogens.


Assuntos
Anticorpos Antibacterianos/imunologia , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/efeitos dos fármacos , Polissacarídeos Bacterianos/imunologia , Animais , Anticorpos Antibacterianos/administração & dosagem , Atividade Bactericida do Sangue , Complexo Burkholderia cepacia/imunologia , Modelos Animais de Doenças , Feminino , Imunoterapia/métodos , Camundongos , Fagocitose
11.
Can J Microbiol ; 58(3): 221-35, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22339239

RESUMO

The Burkholderia cepacia complex (Bcc) is a group of 17 Gram-negative predominantly environmental bacterial species that cause potentially fatal opportunistic infections in cystic fibrosis (CF) patients. Although its prevalence in these individuals is lower than that of Staphylococcus aureus and Pseudomonas aeruginosa , the Bcc remains a serious problem in the CF community because of the pathogenicity, transmissibility, and inherent antibiotic resistance of these organisms. An alternative treatment for Bcc infections that is currently being developed is phage therapy, the clinical use of viruses that infect bacteria. To assess the suitability of individual phage isolates for therapeutic use, the complete genome sequences of a panel of Bcc-specific phages were determined and analyzed. These sequences encode a broad range of proteins with a gradient of relatedness to phage and bacterial gene products from Burkholderia and other genera. The majority of these phages were found not to encode virulence factors, and despite their predominantly temperate nature, a proof-of-principle experiment has shown that they may be modified to a lytic form. Both the genomic characterization and subsequent engineering of Bcc-specific phages are fundamental to the development of an effective phage therapy strategy for these bacteria.


Assuntos
Bacteriófagos/genética , Complexo Burkholderia cepacia/virologia , Genoma Viral/genética , Animais , Bacteriófagos/patogenicidade , Infecções por Burkholderia/terapia , Fibrose Cística/complicações , Genômica , Humanos , Camundongos , Infecções Oportunistas/complicações , Infecções Oportunistas/microbiologia , Infecções Oportunistas/terapia , Fatores de Virulência/genética
12.
Can Respir J ; 18(4): e64-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22059186
13.
J Appl Microbiol ; 110(1): 106-17, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20875034

RESUMO

AIMS: To determine the feasibility of formulating and aerosolizing powders containing bacteriophages KS4-M and ΦKZ for lung delivery and treatment of pulmonary Burkholderia cepacia complex and Pseudomonas aeruginosa infections. METHODS AND RESULTS: Endotoxin-removed bacteriophages KS4-M and ΦKZ were lyophilized in lactose/lactoferrin 60 : 40 w/w matrix and deagglomerated in a mixer mill (without beads) to formulate respirable powders. The powders were then aerosolized using an Aerolizer(®) capsule inhaler. Mass median aerodynamic diameter (MMAD) of this inhalable aerosol was determined using Andersen cascade impactor at 60 l min(-1). Measured MMAD for both types of powders was 3·4 µm, and geometric standard deviation was 1·9-2·0. Viability of bacteriophages delivered distal to an idealized mouth-throat replica was determined from bioassays of samples collected on filters placed after the idealized replica. As a percentage of inhaler load, amount of powder delivered distal to the mouth-throat replica, which is a measure of lung delivery, was 33·7 ± 0·3% for KS4-M and 32·7 ± 0·9% for ΦKZ. Titres collected downstream of the mouth throat were (3·4 ± 2·5) × 10(6) PFU for KS4-M with an Aerolizer capsule load of (9·8 ± 4·8) × 10(6) and (1·9 ± 0·6) × 10(7) for ΦKZ with an Aerolizer capsule load of (6·5 ± 1·9) × 10(7). CONCLUSIONS: Bacteriophages KS4-M and ΦKZ can be lyophilized without significant loss of viability in a lactose/lactoferrin 60 : 40 w/w matrix. The resulting powders can be aerosolized to deliver viable bacteriophages to the lungs. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of lactoferrin-based bacteriophage aerosol powders solidifies the ground for future research on developing novel formulations as an alternative to inhaled antibiotic therapy in patients with cystic fibrosis.


Assuntos
Bacteriófagos , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia , Fibrose Cística/complicações , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Aerossóis , Bacteriófagos/ultraestrutura , Inaladores de Pó Seco , Liofilização , Humanos , Lactoferrina/análise , Pulmão , Nebulizadores e Vaporizadores
14.
Artigo em Inglês | MEDLINE | ID: mdl-22919592

RESUMO

In recent times, increased attention has been given to evaluating the efficacy of phage therapy, especially in scenarios where the bacterial infectious agent of interest is highly antibiotic resistant. In this regard, phage therapy is especially applicable to infections caused by the Burkholderia cepacia complex (BCC) since members of the BCC are antibiotic pan-resistant. Current studies in BCC phage therapy are unique from many other avenues of phage therapy research in that the investigation is not only comprised of phage isolation, in vitro phage characterization and assessment of in vivo infection model efficacy, but also adapting aerosol drug delivery techniques to aerosol phage formulation delivery and storage.


Assuntos
Bacteriófagos/fisiologia , Terapia Biológica/métodos , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia , Infecções Respiratórias/terapia , Aerossóis , Animais , Bacteriófagos/genética , Terapia Biológica/tendências , Complexo Burkholderia cepacia/virologia , Liofilização , Humanos , Myoviridae/genética , Myoviridae/fisiologia , Podoviridae/genética , Podoviridae/fisiologia , Pós , Siphoviridae/genética , Siphoviridae/fisiologia
15.
Appl Microbiol Biotechnol ; 87(1): 31-40, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20390415

RESUMO

The Burkholderia cepacia complex (Bcc) is a group of 17 closely related species of the beta-proteobacteria subdivision that emerged in the 1980s as important human pathogens, especially to patients suffering from cystic fibrosis. Since then, a remarkable progress has been achieved on the taxonomy and molecular identification of these bacteria. Although some progress have been achieved on the knowledge of the pathogenesis traits and virulence factors used by these bacteria, further work envisaging the identification of potential targets for the scientifically based design of new therapeutic strategies is urgently needed, due to the very difficult eradication of these bacteria with available therapies. An overview of these aspects of Bcc pathogenesis and opportunities for the design of future therapies is presented and discussed in this work.


Assuntos
Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/patogenicidade , Fatores de Virulência/metabolismo , Animais , Infecções por Burkholderia/microbiologia , Complexo Burkholderia cepacia/classificação , Complexo Burkholderia cepacia/efeitos dos fármacos , Complexo Burkholderia cepacia/genética , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Humanos , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/genética
16.
J Infect Dis ; 201(2): 264-71, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20001604

RESUMO

The therapeutic potential of bacteriophages (phages) in a mouse model of acute Burkholderia cenocepacia pulmonary infection was assessed. Phage treatment was administered by either intranasal inhalation or intraperitoneal injection. Bacterial density, macrophage inflammatory protein 2 (MIP-2), and tumor necrosis factor alpha (TNF-alpha) levels were significantly reduced in lungs of mice treated with intraperitoneal phages (P < .05). No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with intranasal phages, intraperitoneal ultraviolet-inactivated phages, or intraperitoneal lambda phage control mice. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNF-alpha levels compared with mock-infected/mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic phage administration was more effective than inhalational administration, suggesting that circulating phages have better access to bacteria in lungs than do topical phages.


Assuntos
Bacteriófagos , Terapia Biológica , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/virologia , Infecções Respiratórias/terapia , Administração Intranasal , Animais , Modelos Animais de Doenças , Injeções Intraperitoneais , Camundongos , Infecções Respiratórias/microbiologia
17.
Antimicrob Agents Chemother ; 53(5): 2205-8, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19223640

RESUMO

The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterpillar infection model, we show that BCC phage therapy is an alternative treatment possibility and is highly effective under specific conditions.


Assuntos
Bacteriófagos/fisiologia , Infecções por Burkholderia/terapia , Complexo Burkholderia cepacia/virologia , Modelos Animais de Doenças , Mariposas/crescimento & desenvolvimento , Mariposas/microbiologia , Animais , Infecções por Burkholderia/microbiologia , Hemolinfa/virologia , Humanos , Larva/crescimento & desenvolvimento , Resultado do Tratamento
18.
Infect Immun ; 77(4): 1579-88, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19179415

RESUMO

Burkholderia mallei and B. pseudomallei are important human pathogens and cause the diseases glanders and melioidosis, respectively. Both organisms are highly infectious when inhaled and are inherently resistant to many antimicrobials, thus making it difficult to treat pneumonic Burkholderia infections. We investigated whether it was possible to achieve rapid protection against inhaled Burkholderia infection by using inhaled immunotherapy. For this purpose, cationic liposome DNA complexes (CLDC), which are potent activators of innate immunity, were used to elicit the activation of pulmonary innate immune responses. We found that mucosal CLDC administration before or shortly after bacterial challenge could generate complete or nearly complete protection from inhalational challenge with 100% lethal doses of B. mallei and B. pseudomallei. Protection was found to be dependent on the CLDC-mediated induction of gamma interferon responses in lung tissues and was partially dependent on the activation of NK cells. However, CLDC-mediated protection was not dependent on the induction of inducible nitric oxide synthase, as assessed by depletion studies. We concluded that the potent local activation of innate immune responses in the lung could be used to elicit rapid and nonspecific protection from aerosol exposure to both B. mallei and B. pseudomallei.


Assuntos
Infecções por Burkholderia , Burkholderia mallei/patogenicidade , Burkholderia pseudomallei/patogenicidade , Imunoterapia/métodos , Pneumopatias , Administração por Inalação , Animais , Infecções por Burkholderia/imunologia , Infecções por Burkholderia/microbiologia , Infecções por Burkholderia/prevenção & controle , Infecções por Burkholderia/terapia , Cátions , Linhagem Celular , DNA Bacteriano/administração & dosagem , DNA Bacteriano/genética , DNA Bacteriano/imunologia , Escherichia coli/genética , Mormo/imunologia , Mormo/microbiologia , Mormo/prevenção & controle , Mormo/terapia , Humanos , Interferon gama/biossíntese , Lipossomos/administração & dosagem , Lipossomos/imunologia , Pneumopatias/imunologia , Pneumopatias/microbiologia , Pneumopatias/prevenção & controle , Pneumopatias/terapia , Macrófagos Alveolares/microbiologia , Melioidose/imunologia , Melioidose/microbiologia , Melioidose/prevenção & controle , Melioidose/terapia , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/administração & dosagem , Plasmídeos/genética , Plasmídeos/imunologia
19.
Singapore Med J ; 49(9): e219-21, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18830523

RESUMO

We report a 64-year-old man presenting with meningitis caused by Burkholderia pseudomallei predisposed by persistent aortic graft infection following inadequate treatment of a melioidotic mycotic aneurysm. The relapse of melioidosis presenting as acute meningitis is a unique event. Successful treatment of deep-seated melioidosis can only be achieved when robust antimicrobial therapy is combined with appropriate surgical debridement.


Assuntos
Aneurisma Infectado/complicações , Aneurisma Infectado/terapia , Infecções por Burkholderia/etiologia , Infecções por Burkholderia/microbiologia , Burkholderia pseudomallei/metabolismo , Melioidose/complicações , Melioidose/terapia , Meningite/etiologia , Meningite/microbiologia , Administração Oral , Antibacterianos/uso terapêutico , Aorta/microbiologia , Aorta/transplante , Implante de Prótese Vascular/efeitos adversos , Infecções por Burkholderia/terapia , Doxiciclina/uso terapêutico , Humanos , Masculino , Meningite/terapia , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
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