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1.
BMC Microbiol ; 24(1): 172, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38760693

RESUMO

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.


Assuntos
Microbiota , Infecções por Mycobacterium não Tuberculosas , RNA Ribossômico 16S , Escarro , Humanos , Escarro/microbiologia , Masculino , Feminino , Microbiota/genética , Microbiota/efeitos dos fármacos , Idoso , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/efeitos dos fármacos , DNA Bacteriano/genética , Pneumopatias/microbiologia , Pneumopatias/tratamento farmacológico
2.
Artigo em Inglês | MEDLINE | ID: mdl-33685889

RESUMO

We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

3.
Antimicrob Agents Chemother ; 66(10): e0077422, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36165626

RESUMO

Short-term intravenous tigecycline therapy during a 1-month initial phase may improve early microbiological response in patients with Mycobacterium abscessus pulmonary disease (PD). However, short-term use of tigecycline did not improve the long-term culture conversion rate of M. abscessus PD. Further studies on the efficacy of prolonged intravenous tigecycline-containing regimens are needed.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Tigeciclina/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/uso terapêutico , Pneumopatias/tratamento farmacológico , Testes de Sensibilidade Microbiana
4.
Antimicrob Agents Chemother ; 66(4): e0202721, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35266825

RESUMO

We evaluated the associations between the in vitro activities of ethambutol and rifampin and clinical outcomes of Mycobacterium avium complex (MAC) pulmonary disease (PD). Among 158 patients with MAC-PD, there was no relationship between high MICs for ethambutol and/or rifampin and treatment failure for MAC-PD. Ethambutol and rifampin resistance was common among MAC isolates (rates of 87% and 59%, respectively), but mutations in embB, rpoB, and rpoC were rare, with detection in only 4% of the drug-resistant MAC isolates.


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Etambutol/farmacologia , Etambutol/uso terapêutico , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Rifampina/farmacologia , Rifampina/uso terapêutico
5.
Antimicrob Agents Chemother ; 65(7): e0230620, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33903101

RESUMO

We evaluated the in vitro activities of oxazolidinone antibiotics, including linezolid, sutezolid, and delpazolid, against clinical nontuberculous mycobacteria (NTM) isolates. Regardless of macrolide resistance, for Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii, sutezolid showed the lowest MIC and minimal bactericidal concentration (MBC) values among oxazolidinone antibiotics. However, for Mycobacterium abscessus and Mycobacterium massiliense, the MIC and MBC for all oxazolidinone antibiotics showed similar values. Oxazolidinone antibiotics warrant further investigation as potential treatment for NTM.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Oxazolidinonas , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Oxazolidinonas/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-31182533

RESUMO

We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. kansasii Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment.


Assuntos
Antibacterianos/farmacologia , Antituberculosos/farmacologia , Diarilquinolinas/farmacologia , Macrolídeos/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Nitroimidazóis/farmacologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Oxazóis/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium kansasii/efeitos dos fármacos
7.
J Clin Microbiol ; 57(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31167842

RESUMO

We evaluated the GenoType NTM-DR (NTM-DR) line probe assay for identifying Mycobacterium avium complex (MAC) species and Mycobacterium abscessus subspecies and for determining clarithromycin and amikacin resistance. Thirty-eight reference strains and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and/or amikacin-resistant strains, were involved. The performance of the NTM-DR assay in rapid identification was evaluated by comparison with results of multigene sequence-based typing, whereas performance in rapid detection of clarithromycin and amikacin resistance was evaluated by comparison with sequencing of the erm(41), rrl, and rrs genes and drug susceptibility testing (DST). The accuracies of MAC and M. abscessus (sub)species identification were 92.1% (35/38) and 100% (145/145) for the 38 reference strains and 145 clinical isolates, respectively. Three MAC strains other than M. intracellulare were found to cross-react with the M. intracellulare probe in the assay. Regarding clarithromycin resistance, NTM-DR detected rrl mutations in 52 isolates and yielded 99.3% (144/145) and 98.6% (143/145) concordant results with sequencing and DST, respectively. NTM-DR sensitivity and specificity in the detection of clarithromycin resistance were 96.3% (52/54) and 100% (91/91), respectively. The NTM-DR yielded accurate erm(41) genotype results for all 87 M. abscessus isolates. Regarding amikacin resistance, NTM-DR detected rrs mutations in five isolates and yielded 99.3% (144/145) and 97.9% (142/145) concordant results with sequencing and DST, respectively. Our results indicate that the NTM-DR assay is a straightforward and accurate approach for discriminating MAC and M. abscessus (sub)species and for detecting clarithromycin and amikacin resistance mutations and that it is a useful tool in the clinical setting.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Técnicas de Genotipagem , Mycobacterium abscessus/genética , Complexo Mycobacterium avium/genética , Amicacina/farmacologia , Claritromicina/farmacologia , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Mutação , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/microbiologia
8.
J Nanosci Nanotechnol ; 19(2): 634-639, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30360134

RESUMO

The aim of this work was to prepare and assess a self-nanoemulsifying drug delivery system (SNEDDS) containing water-insoluble orlistat that was used for the inhibition of lipase activity in gastrointestinal lumen. The pseudo-ternary phase diagram, composed of orlistat and medium chain triglycerides (MCT) as oil phase and Cremophor EL as surfactant, was made for the confirmation of giving SNEDDS preconcentrate. The physical state, particle size dispersed in water, dissolution and lipase inhibition of SNEDDS preconcentrates were investigated. The appointed SNEDDS preconcentrates in the pseudo-ternary phase diagram showed no endothermic peak of orlistat and a liquid state. The particle sizes of SNEDDS dispersed with water were uniform and in the range of <200 nm. In the dissolution test, the liquid SNEDDS preconcentrate and solid state mixture exhibited 90.89±2.03% versus 22.42±3.71% at 60 min., respectively, whereas the raw orlistat showed no significant dissolution rate. The SNEDDS preconcentrate showed a lipase inhibition of 92.42±1.58% until 60 min., with no significant inhibition activity of orlistat. Therefore, the SNEDDS preconcentrate presented in this work solubilized orlistat and increased its dissolution rate, and resulted in sufficient inhibitory action on lipase.


Assuntos
Sistemas de Liberação de Medicamentos , Lipase , Nanopartículas , Orlistate/administração & dosagem , Administração Oral , Disponibilidade Biológica , Emulsões , Tamanho da Partícula , Solubilidade , Tensoativos
9.
J Nanosci Nanotechnol ; 19(2): 640-645, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30360135

RESUMO

Ecabet has a mucosal protection and anti-Helicobacter pylori effect only by local action in the gastric mucous layer, due to an extremely poor absorption into the systemic blood circulation. The aim of the present work was to develop chitosan-ecabet electrolyte complex (ChE) for the enhanced mucosal drug delivery. ChEs were prepared with various ecabet-chitosan concentration ratios. Entrapment efficiency (%), sedimentation volume (%), transmission electron microscopy (TEM), FT-IR spectrum, and drug release were investigated. ChEs were prepared by the simple mixing method in a pH-adjusted solution based on the electrostatic interaction between the sulfonate (negatively charged) group from ecabet and the amine (positively charged) group from chitosan. Sedimentation volume and entrapment efficiency at the same concentration of ecabet sodium with that of chitosan resulted in 53.6% and 86.75%, respectively, suggesting a high degree of forming complex. In TEM images, the complex was approximately 200 nm in particle size and had loosely entangled particles. Forming complex of ChEs was supported by new bands appearance in the FT-IR spectrum. In the drug release study using dialysis membrane sac, ChEs showed a sustainable release up to 80% during 12 h as compared to ecabet sodium suspension at pH 1.2 medium. Based on the results of this work, ChE would be a promising drug delivery system for gastric mucosa.


Assuntos
Antiulcerosos , Quitosana , Diterpenos , Abietanos , Eletrólitos , Diálise Renal , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Clin Infect Dis ; 64(3): 309-316, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011608

RESUMO

BACKGROUND: Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. METHODS: Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. RESULTS: Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. CONCLUSIONS: Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. CLINICAL TRIALS REGISTRATION: NCT00970801.


Assuntos
Antibacterianos/uso terapêutico , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Idoso , Antibacterianos/farmacologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Resistência Microbiana a Medicamentos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/isolamento & purificação , Recidiva , Estudos Retrospectivos , Escarro/microbiologia , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-27895018

RESUMO

In this study, we analyzed the frequency of the AbGRI1-type genomic island (GI) and its association with genotypes. We obtained 130 Acinetobacter baumannii isolates causing bloodstream infections from patients in South Korea. Antimicrobial susceptibility testing and multilocus sequence typing were performed. The presence of AbGRI1-type GIs and their structures were determined by sequential PCR and sequencing. Ninety-eight isolates (75.3%) representing 14 sequence types (STs) belonged to clonal complex 208 (CC208), corresponding to global clone 2 (GC2). AbGRI1-type GIs interrupted the comM gene in 107 isolates (82.4%). Four types of GIs were identified: Tn6022 (50 isolates; 46.7%), AbaR4 (23 isolates; 21.5%), Tn6166 (10 isolates; 9.3%), and Tn6166/Tn2006 (24 isolates; 22.4%). In the 50 isolates with Tn6022, Tn2006 or Tn2008B, both containing ISAba1-blaOXA-23, was present in sites other than GIs in 3 or 28 isolates, respectively. In the 10 isolates with Tn6166, Tn2008B was identified in one isolate. AbGRI1-type GIs were identified nearly exclusively in CC208 isolates, with the exception of nine non-CC208 isolates (AbaR4 in eight ST229 isolates and Tn6022 in one ST1244 isolate). Within CC208 isolates, there was evidence of frequent recombination events, in both housekeeping genes and AbGRI1-type GIs, contributing to genotype diversification and the emergence of carbapenem resistance.


Assuntos
Acinetobacter baumannii/genética , Ilhas Genômicas/genética , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Elementos de DNA Transponíveis/genética , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , República da Coreia , beta-Lactamases/genética , beta-Lactamases/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-28348153

RESUMO

Patients with lung disease caused by Mycobacterium abscessus subsp. abscessus (here M. abscessus) typically have poor treatment outcomes. Although clofazimine (CFZ) has been increasingly used in the treatment of M. abscessus lung disease in clinical practice, there are no reported data on its effectiveness for this disease. This study sought to evaluate the clinical efficacy of a CFZ-containing regimen for the treatment of M. abscessus lung disease. We performed a retrospective review of the medical records of 42 patients with M. abscessus lung disease who were treated with CFZ-containing regimens between November 2013 and January 2015. CFZ was administered in combination with other antibiotics as an initial antibiotic regimen in 15 (36%) patients (initial treatment group), and it was added to an existing antibiotic regimen for refractory M. abscessus lung disease in 27 (64%) patients (salvage treatment group). Overall, there was an 81% treatment response rate based on symptoms and a 31% response rate based on radiographic findings. Conversion to culture-negative sputum samples was achieved in 10 (24%) patients after CFZ-containing antibiotic treatment, and during treatment, there were significant decreases in the positivity of semiquantitative sputum cultures for acid-fast bacilli in both the initial (P = 0.018) and salvage (P = 0.001) treatment groups. Our study suggests that CFZ-containing regimens may improve treatment outcomes in patients with M. abscessus lung disease and that a prospective evaluation of CFZ in M. abscessus lung disease is warranted.


Assuntos
Clofazimina/uso terapêutico , Pneumopatias/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Quimioterapia Combinada , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/patogenicidade , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/patogenicidade , Estudos Retrospectivos , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-27872066

RESUMO

Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.


Assuntos
Antibacterianos/farmacologia , Pneumopatias/microbiologia , Macrolídeos/farmacologia , Mycobacterium/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Macrolídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mycobacterium/patogenicidade , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/microbiologia , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/patogenicidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-28739795

RESUMO

Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant Mycobacterium abscessus subsp. abscessus This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Pneumopatias/tratamento farmacológico , Macrolídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/efeitos dos fármacos , Idoso , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium abscessus/genética , Estudos Retrospectivos , Escarro/microbiologia , Resultado do Tratamento
15.
Antimicrob Agents Chemother ; 60(11): 6758-6765, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27572413

RESUMO

Macrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due to Mycobacterium avium complex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form. M. intracellulare was the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Mutação , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Idoso , Combinação de Medicamentos , Etambutol/uso terapêutico , Feminino , Expressão Gênica , Humanos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Macrolídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/crescimento & desenvolvimento , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecção por Mycobacterium avium-intracellulare/mortalidade , Infecção por Mycobacterium avium-intracellulare/patologia , RNA Ribossômico 23S/genética , Estudos Retrospectivos , Rifampina/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
16.
Opt Express ; 24(2): A350-7, 2016 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-26832587

RESUMO

CdSe/CdS/ZnS core-shell-shell quantum dots (QDs) were synthesized by using a solution process. High-resolution transmission electron microscopy images and energy dispersive spectroscopy profiles confirmed that stoichiometric CdSe/CdS/ZnS core-shell-shell QDs were formed. Ultraviolet-visible absorption and photoluminescence (PL) spectra of CdSe/CdS/ZnS core-shell-shell QDs showed the dominant excitonic transitions from the ground electronic subband to the ground hole subband (1S(e)-1S(3/2)(h)). The PL mechanism is suggested; the carriers generated by the exciting high-energy photons in the shell region are relaxed to the band-edge states of the core region and recombined to emit lower-energy photons. The activation energy of the carriers confined in the CdSe/CdS/ZnS core-shell-shell QDs, as obtained from temperature-dependent PL spectra, was 200 meV. The quantum efficiency of the CdSe/CdS/ZnS core-shell-shell QDs at 300 K was estimated to be approximately 57%.

17.
Pflugers Arch ; 467(8): 1663-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25231973

RESUMO

Raloxifene is widely used for the treatment and prevention of postmenopausal osteoporosis. We examined the effects of raloxifene on the Kv4.3 currents expressed in Chinese hamster ovary (CHO) cells using the whole-cell patch-clamp technique and on the long-term modulation of Kv4.3 messenger RNA (mRNA) by real-time PCR analysis. Raloxifene decreased the Kv4.3 currents with an IC50 of 2.0 µM and accelerated the inactivation and activation kinetics in a concentration-dependent manner. The inhibitory effects of raloxifene on Kv4.3 were time-dependent: the association and dissociation rate constants for raloxifene were 9.5 µM(-1) s(-1) and 23.0 s(-1), respectively. The inhibition by raloxifene was voltage-dependent (δ = 0.13). Raloxifene shifted the steady-state inactivation curves in a hyperpolarizing direction and accelerated the closed-state inactivation of Kv4.3. Raloxifene slowed the time course of recovery from inactivation, thus producing a use-dependent inhibition of Kv4.3. ß-Estradiol and tamoxifen had little effect on Kv4.3. A preincubation of ICI 182,780, an estrogen receptor antagonist, for 1 h had no effect on the inhibitory effect of raloxifene on Kv4.3. The metabolites of raloxifene, raloxifene-4'-glucuronide and raloxifene-6'-glucuronide, had little or no effect on Kv4.3. Coexpression of KChIP2 subunits did not alter the drug potency and steady-state inactivation of Kv4.3 channels. Long-term exposure to raloxifene (24 h) significantly decreased the expression level of Kv4.3 mRNA. This effect was not abolished by the coincubation with ICI 182,780. Raloxifene inhibited Kv4.3 channels by interacting with their open state during depolarization and with the closed state at subthreshold potentials. This effect was not mediated via an estrogen receptor.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Cloridrato de Raloxifeno/farmacologia , Receptores de Estrogênio , Canais de Potássio Shal/antagonistas & inibidores , Animais , Células CHO , Clonagem Molecular , Cricetulus , Relação Dose-Resposta a Droga , Regulação para Baixo , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Cinética , Proteínas Interatuantes com Canais de Kv/genética , Proteínas Interatuantes com Canais de Kv/metabolismo , Potenciais da Membrana , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Potássio Shal/genética , Canais de Potássio Shal/metabolismo , Tamoxifeno/farmacologia , Transfecção
18.
Antimicrob Agents Chemother ; 59(9): 5824-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26100696

RESUMO

To investigate the presence and structure of AbaR-type genomic islands (GIs) in non-Acinetobacter baumannii isolates, a total of 155 non-baumannii Acinetobacter isolates from a South Korean hospital were analyzed. GIs were found in three Acinetobacter nosocomialis and two Acinetobacter seifertii isolates. Their structures were similar to those in A. baumannii isolates from Asian countries, including South Korea. The existence of AbaR-type GIs in non-baumannii Acinetobacter isolates is believed to be due to interspecies transfer of GI.


Assuntos
Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Ilhas Genômicas/genética , Acinetobacter baumannii/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Hospitais , Testes de Sensibilidade Microbiana , República da Coreia
19.
Microbiology (Reading) ; 161(Pt 5): 973-979, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25750083

RESUMO

Recently, it has been reported that some non-typable (NT) Streptococcus pneumoniae isolates from Korea and other countries contained a novel gene pspK in the capsular polysaccharide synthesis (cps) locus. In this study, we investigated the presence of pspK in 120 NT S. pneumoniae isolates from 12 Asian countries; isolate characteristics were also examined. The presence of pspK was assayed by PCR. Clonality of NT S. pneumoniae isolates containing pspK was investigated by MLST and PFGE. Antimicrobial susceptibility testing was performed and the structure of pspK was also determined. Nineteen NT isolates (15.8 %) were identified as containing pspK: two isolates from Korea, four from Vietnam, two from Hong Kong, eight from Thailand, and one each from Taiwan, the Philippines and Saudi Arabia. Seven isolates from Korea, Vietnam and Thailand were identified as ST1106, whereas just one or two belonged to ST310, ST393, ST10137, ST2754 or ST4136. All but one of the ST1106 NT isolates showed non-susceptibility to penicillin, and all isolates were resistant to cefuroxime, erythromycin, clindamycin and trimethoprim/sulfamethoxazole. The structure of pspK was similar amongst 20 isolates, which had a R1-R2-like region and a variable number of repeats in the repetitive region. However, one isolate (P05-11) from the Philippines lacked the R1-R2 region. NT S. pneumoniae isolates containing pspK were distributed across several Asian countries. Although MLST analysis suggested that most pspK-containing NT S. pneumoniae isolates may have emerged independently, ST1106 isolates with the selective advantage of antimicrobial resistance may have disseminated clonally throughout the countries.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Antibacterianos/farmacologia , Ásia/epidemiologia , Farmacorresistência Bacteriana/genética , Genótipo , Geografia , Humanos , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/epidemiologia , Prevalência , Streptococcus pneumoniae/isolamento & purificação
20.
Opt Express ; 23(9): 11211-20, 2015 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-25969217

RESUMO

Organic light-emitting devices (OLEDs) were fabricated utilizing a poly(4-butylphenyl-diphenyl-amine) (poly-TPD):dodecanethiol functionalized Au (DDT-Au) nanocomposite (NC) layer to enhance their current efficiency. The photoluminescence intensity of the poly-TPD:DDT-Au NC film at 514 nm was significantly increased, being about 1.3 times that of the poly-TPD film due to the coupling between the excitons in the emitting layer and the localized surface plasmonic resonance of the DDT-Au nanoparticles. The current efficiency of the green OLEDs with a poly-TPD:DDT-Au NC layer at 1000 cd/m2 was 3.1 cd/A larger than that with a poly-TPD layer, resulting in an enhanced out-coupling efficiency due to the coupling effect.

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