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1.
J Infect Dis ; 230(2): e241-e246, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38150401

RESUMO

Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While ß-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral ß-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual ß-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.


Assuntos
Antibacterianos , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare , beta-Lactamas , Humanos , Complexo Mycobacterium avium/efeitos dos fármacos , beta-Lactamas/uso terapêutico , beta-Lactamas/administração & dosagem , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Administração Oral , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Testes de Sensibilidade Microbiana
2.
Clin Infect Dis ; 78(6): 1690-1697, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38563246

RESUMO

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.


Assuntos
Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Qualidade de Vida , Humanos , Masculino , Feminino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , República da Coreia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Micobactérias não Tuberculosas/efeitos dos fármacos , Resultado do Tratamento
3.
J Clin Immunol ; 44(4): 84, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578320

RESUMO

PURPOSE: Patients with STAT1 gain-of-function (GOF) mutations often exhibit autoimmune features. The JAK1/2 inhibitor ruxolitinib can be administered to alleviate autoimmune symptoms; however, it is unclear how immune cells are molecularly changed by ruxolitinib treatment. Then, we aimed to investigate the trnscriptional and epigenetic status of immune cells before and after ruxolitinib treatment in a patient with STAT1 GOF. METHODS: A patient with a heterozygous STAT1 GOF variant (p.Ala267Val), exhibiting autoimmune features, was treated with ruxolitinib, and peripheral blood mononuclear cells (PBMCs) were longitudinally collected. PBMCs were transcriptionally analyzed by single-cell cellular indexing of the transcriptomes and epitopes by sequencing (CITE-seq), and epigenetically analyzed by assay of transposase-accessible chromatin sequencing (ATAC-seq). RESULTS: CITE-seq analysis revealed that before treatment, the patient's PBMCs exhibited aberrantly activated inflammatory features, especially IFN-related features. In particular, monocytes showed high expression levels of a subset of IFN-stimulated genes (ISGs). Ruxolitinib treatment substantially downregulated aberrantly overexpressed ISGs, and improved autoimmune features. However, epigenetic analysis demonstrated that genetic regions of ISGs-e.g., STAT1, IRF1, MX1, and OAS1-were highly accessible even after ruxolitinib treatment. When ruxolitinib was temporarily discontinued, the patient's autoimmune features were aggravated, which is in line with sustained epigenetic abnormality. CONCLUSIONS: In a patient with STAT1 GOF, ruxolitinib treatment improved autoimmune features and downregulated aberrantly overexpressed ISGs, but did not correct epigenetic abnormality of ISGs.


Assuntos
Mutação com Ganho de Função , Pirazóis , Fator de Transcrição STAT1 , Humanos , Mutação com Ganho de Função/genética , Leucócitos Mononucleares/metabolismo , Nitrilas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Fator de Transcrição STAT1/genética
4.
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
5.
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.

6.
Lancet ; 400(10362): 1522-1530, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36522208

RESUMO

BACKGROUND: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. METHODS: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. FINDINGS: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. INTERPRETATION: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. FUNDING: Korea Disease Control and Prevention Agency, South Korea.


Assuntos
Pirazinamida , Tuberculose Resistente a Múltiplos Medicamentos , Masculino , Feminino , Humanos , Pirazinamida/uso terapêutico , Linezolida/uso terapêutico , Levofloxacino/uso terapêutico , Fluoroquinolonas/uso terapêutico , Quimioterapia Combinada , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Resultado do Tratamento
7.
J Clin Microbiol ; 61(1): e0108622, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36602360

RESUMO

The World Health Organization recently lowered the rifampin (RIF) critical concentration (CC) for drug-susceptibility testing (DST) of Mycobacterium tuberculosis complex (MTBC) using the mycobacterial growth indicator tube (MGIT) 960 system. Here, we evaluated the diagnostic performance of the MGIT system with the revised CC for determining MTBC RIF resistance with 303 clinical MTBC isolates, including 122 isolates with rpoB mutations, of which 32 had single borderline-resistance mutations, and 181 wild-type rpoB isolates. The phenotypic RIF resistance was determined via the absolute concentration method (AC) and via MGIT using both previous (1 mg/L) and revised (0.5 mg/L) CCs for the latter method. The diagnostic accuracy of each phenotypic DST (pDST) was assessed based on rpoB genotyping as the reference standard. The overall sensitivity of the AC was 95.1% (95% confidence interval [CI], 89.6 to 98.2%), while the MGIT results with previous and revised CCs were 82.0% (95% CI 74.0 to 88.3%) and 83.6% (95% CI 75.8 to 89.7%), respectively. The 32 MTBC isolates with single borderline-resistance mutations showed a wide range of MICs, and sensitivity was not significantly increased by reducing the MGIT CC. All 181 wild-type rpoB isolates were RIF-susceptible in the AC and with MGIT using the previous CC, whereas 1 isolate was misclassified as RIF-resistant with the revised CC. Our results demonstrate that the overall diagnostic performances of the MGIT DST with the revised RIF CC and previous CC were comparable. A further large-scale study is required to demonstrate the optimal RIF CC for MGIT.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , RNA Polimerases Dirigidas por DNA/genética , Testes de Sensibilidade Microbiana , Mutação , Rifampina/farmacologia , Avaliação Pré-Clínica de Medicamentos
8.
Clin Lab ; 69(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37436396

RESUMO

BACKGROUND: Rapid and accurate identification of nontuberculous mycobacteria (NTM) species is essential for the diagnosis and treatment of NTM disease. MolecuTech REBA Myco-ID (YD Diagnostics, Yongin, Korea) is a line probe assay for identification of NTM species and can be performed using HybREAD480, an instrument for automating the post-PCR steps. In this study, we assessed the performance of MolecuTech REBA Myco-ID using HybREAD480. METHODS: Seventy-four reference strains, including 65 Mycobacterium strains and nine non-Mycobacterium strains within the order Mycobacteriales, were used to determine the analytical specificity of MolecuTech REBA Myco-ID. The clinical performance of this assay was evaluated with 192 clinical Mycobacterium strains, and the assay results were compared to those of multigene sequencing-based typing. RESULTS: The accuracy of MolecuTech REBA Myco-ID for the 74 reference strains and 192 clinical strains was 77.0% (57/74; 95% confidence interval [CI], 65.8 - 86.0%) and 94.3% (181/192; 95% CI, 90.0 - 97.1%), respectively. Although some rarely isolated NTM species are misidentified, the most commonly isolated NTM species, including M. avium complex, M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum com-plex, were all correctly identified. Of note, all M. lentiflavum strains tested (reference strain, n = 1; clinical strain, n = 10) were misidentified as M. gordonae. CONCLUSIONS: MolecuTech REBA Myco-ID using HybREAD480 was accurate for identifying commonly isolated NTM species and for discriminating between M. abscessus subsp. abscessus and M. abscessus subsp. massiliense. However, the main limitations of this assay, including misidentification of some rarely isolated NTM species and cross-reactivity between M. lentiflavum and M. gordonae, should be considered.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Humanos , Micobactérias não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , Escarro/microbiologia
9.
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
10.
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
11.
J Infect Chemother ; 28(8): 1098-1104, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35461769

RESUMO

INTRODUCTION: Whether prolonged intravenous amikacin treatment would lead to better treatment results in patients with Mycobacterium abscessus subspecies abscessus (M. abscessus) pulmonary disease (PD) is unknown. We investigated the efficacy of continued amikacin treatment for the microbiological outcome of M. abscessus PD patients with persistent culture positivity after treatment initiation. METHODS: We retrospectively evaluated 62 patients with M. abscessus PD who were treated with intravenous amikacin and beta-lactams along with a macrolide-based regimen at 3 tertiary referral centers in South Korea. The intravenous antibiotic treatment duration was determined by the attending physician. RESULTS: The median treatment durations with amikacin and beta-lactam in the 62 patients were 25.1 and 8.2 weeks, respectively. The overall microbiological cure rate was 29.0%. Among the 62 patients, 44 showed persistent culture positivity at 8 weeks after treatment with an amikacin-containing multidrug regimen. The median parenteral amikacin treatment duration after 8 weeks in these patients was 18.0 weeks. The conditional probability of microbiological cure with continuation of the amikacin-containing regimen in these patients was 18.2% (95% confidence interval 8.2-32.7). Additionally, the conditional probability of microbiological cure in the 34 patients with persistent culture positivity at 12 weeks was 8.8% (95% confidence interval 1.9-23.7). After 16 weeks, the conditional probability of microbiological cure decreased further, reaching 0% at 28 weeks after treatment initiation. CONCLUSION: The continuation of intravenous amikacin therapy was usually not followed by culture conversion in M. abscessus PD patients with persistent sputum culture positivity after treatment initiation.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Amicacina , Antibacterianos , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
12.
Am J Respir Crit Care Med ; 203(2): 230-236, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32721164

RESUMO

Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed.Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease.Methods: We included patients age ≥20 years with newly diagnosed nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort.Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m2 (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval, 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval, 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5.Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense.


Assuntos
Regras de Decisão Clínica , Infecções por Mycobacterium não Tuberculosas/mortalidade , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
J Korean Med Sci ; 37(32): e250, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971764

RESUMO

The aim of our study was to investigate the incidence of and risk factors for coronavirus disease 2019 (COVID-19) in patients with non-tuberculous mycobacterial-pulmonary disease (NTM-PD). A total of 3,866 patients with NTM-PD were retrospectively identified from a single center. Compared to the general population of Korea, patients with NTM-PD had a substantially increased age-standardized incidence of COVID-19 from January 2020 to February 2021 (2.1% vs. 0.2%). The odds of being infected with COVID-19 was particularly higher in patients who received treatment for NTM-PD than in those who did not receive treatment for NTM-PD (adjusted odd ratio = 1.99, 95% confidence interval = 1.09-3.64, P = 0.026). Patients with NTM-PD might be regarded as a high-risk group for COVID-19 and may need a more proactive preventive strategy for COVID-19 and other pandemics in the future.


Assuntos
COVID-19 , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , COVID-19/epidemiologia , Humanos , Incidência , Pneumopatias/epidemiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , República da Coreia/epidemiologia , Estudos Retrospectivos
14.
Clin Infect Dis ; 72(10): e610-e619, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32926135

RESUMO

BACKGROUND: Population-based studies on the mortality burden of nontuberculous mycobacteria (NTM) infection are lacking. We compared the long-term mortality of NTM-infected patients with tuberculosis (TB)-patients and the general population, and investigated mortality-associated factors. METHODS: We analyzed nationwide-data from the Korean National Health Insurance and Korea-Statistical Office between 2002 and 2017. NTM infection was identified using the International Classification of Disease, Tenth Revision code, with one-to-one matching to TB patients and general population controls. RESULTS: A total of 530 401 individuals were analyzed, including 183 267 with NTM infections; 166 666 with TB; and 180 468 controls. The overall 6-, 10-, and 14-year cumulative survival probabilities in the NTM group were 86.3%, 80.8%, and 77.1%, respectively, which were significantly lower than those of the TB or control groups (log-rank P < .0001). In cases of NTM and TB coinfection, the overall 6-, 10-, and 14-year cumulative survival probabilities were 75.1%, 65.4%, and 57.0%, respectively. Multivariable analysis indicated that old age, male gender, province, and various respiratory or nonrespiratory comorbidities were significantly associated with mortality of NTM infection. The use of a macrolide (more than 1 year) negatively correlated with mortality of NTM infection (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] .53-.71), regardless of azithromycin (aHR 0.60, 95% CI .43-.85) or clarithromycin use (aHR 0.63, 95% CI .53-.75). CONCLUSIONS: NTM-infected patients had poor prognosis when compared to TB patients or the general population, especially for NTM and TB coinfection. NTM mortality was associated with certain demographic characteristics, but long-term use of macrolides may provide survival benefits.


Assuntos
Coinfecção , Infecções por Mycobacterium não Tuberculosas , Tuberculose , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas , Prognóstico , República da Coreia/epidemiologia
15.
Clin Infect Dis ; 73(1): e256-e259, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910814

RESUMO

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Humanos , Pneumopatias/induzido quimicamente , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Micobactérias não Tuberculosas
16.
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
17.
Eur Respir J ; 58(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33542050

RESUMO

RATIONALE: Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear. OBJECTIVES: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen. METHODS: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping. RESULTS: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry. CONCLUSIONS: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Estudo de Associação Genômica Ampla , Humanos , Infecções por Mycobacterium não Tuberculosas/genética , Complexo Mycobacterium avium , Micobactérias não Tuberculosas
18.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31619468

RESUMO

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Seguimentos , Humanos , Masculino , Complexo Mycobacterium avium , Micobactérias não Tuberculosas , Prognóstico , Estudos Retrospectivos
19.
Emerg Infect Dis ; 25(3): 569-572, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30789139

RESUMO

The prevalence and incidence of nontuberculous mycobacterial (NTM) infections increased in South Korea from 2007 to 2016. Annual prevalence of NTM infection increased to 39.6 cases/100,000 population in 2016 and annual incidence to 19.0 cases/100,000 population. Overall prevalence for the study period was higher in the elderly, in females, and in cities.


Assuntos
Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/história , Infecções por Mycobacterium não Tuberculosas/microbiologia , Prevalência , Vigilância em Saúde Pública , República da Coreia/epidemiologia , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-31611366

RESUMO

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary Mycobacterium avium complex pulmonary disease (MAC-PD). Twenty-nine (76%) of 38 patients achieved sputum culture conversion after 12 months of treatment, and sputum smear positivity was an independent factor for failure to achieve culture conversion (adjusted odds ratio, 26.7; 95% confidence interval, 2.1 to 339.9; P = 0.011). Intermittent azithromycin and ethambutol may be an optional treatment regimen for noncavitary MAC-PD.


Assuntos
Antituberculosos/uso terapêutico , Azitromicina/uso terapêutico , Etambutol/uso terapêutico , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/patogenicidade , Índice de Massa Corporal , Quimioterapia Combinada/métodos , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Razão de Chances , Resultado do Tratamento
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