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1.
Antimicrob Agents Chemother ; 68(3): e0115723, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38259101

RESUMO

Mycobacterium avium complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model. THP-1 cells, which are monocytes isolated from peripheral blood from an acute monocytic leukemia patient, were infected with M. avium ATCC 700898 and exposed to a regimen of azithromycin and ethambutol with either rifampicin or clofazimine. Intrapulmonary pharmacokinetic profiles of azithromycin, ethambutol, and rifampicin were simulated. For clofazimine, a steady-state average concentration was targeted. Drug concentrations and bacterial densities were monitored over 21 days. Exposures to azithromycin and ethambutol were 20%-40% lower than targeted but within clinically observed ranges. Clofazimine exposures were 1.7 times higher than targeted. Until day 7, both regimens were able to maintain stasis. Thereafter, regrowth was observed for the rifampicin-containing regimen, while the clofazimine-containing regimen yielded a 2 Log10 colony forming unit (CFU) per mL decrease in bacterial load. The clofazimine regimen also successfully suppressed the emergence of macrolide tolerance. In summary, substitution of rifampicin with clofazimine in the hollow-fiber model improved the antimycobacterial activity of the regimen. Clofazimine-containing regimens merit investigation in clinical trials.


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Etambutol/farmacologia , Etambutol/uso terapêutico , Azitromicina/farmacologia , Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Quimioterapia Combinada , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Complexo Mycobacterium avium , Pneumopatias/microbiologia
2.
Clin Chest Med ; 44(4): 861-868, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37890922

RESUMO

Rates of nontuberculous mycobacterial pulmonary disease are increasing worldwide, particularly in the United States and other developed countries. While multidrug antimicrobial therapy is the mainstay of treatment, surgical resection has emerged as an important adjunct. In this article, we will review the indications for surgery, preoperative considerations, surgical techniques, and postoperative outcomes.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Estados Unidos , Pneumonectomia/métodos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/cirurgia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/cirurgia , Pneumopatias/microbiologia , Micobactérias não Tuberculosas
3.
Antimicrob Agents Chemother ; 67(11): e0100323, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37843254

RESUMO

This study retrospectively analyzed the treatment outcomes of 110 patients with non-cavitary nodular bronchiectatic-type Mycobacterium avium complex pulmonary disease who received intermittent or daily treatment with a three-drug oral antibiotic regimen (i.e., a macrolide, ethambutol, and rifampin) at a tertiary referral center in South Korea. Among these patients, 36 had sputum smear positivity. Of these 36 patients, intermittent treatment led to a lower culture conversion rate than daily treatment [50.0% (8/16) vs 85.0% (17/20), P = 0.034].


Assuntos
Bronquiectasia , Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Complexo Mycobacterium avium , Estudos Retrospectivos , Escarro/microbiologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Antibacterianos/uso terapêutico , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Resultado do Tratamento
4.
Front Cell Infect Microbiol ; 13: 1205225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424783

RESUMO

Background: The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention. Methods: NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis. Results: 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them. Conclusion: The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.


Assuntos
Bronquiectasia , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Seguimentos , Centros de Atenção Terciária , Azitromicina , Pneumopatias/microbiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico
5.
Sci Rep ; 13(1): 7348, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147519

RESUMO

This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17-24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39-53%) and 43% (95% CI 31-55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Pneumonia , Humanos , Masculino , Estudos Retrospectivos , Infecções por Mycobacterium não Tuberculosas/patologia , Pneumopatias/microbiologia , Progressão da Doença
6.
Med Clin (Barc) ; 160(12): 561-563, 2023 06 23.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37127459

RESUMO

INTRODUCTION: The objective of our study was to evaluate the frequency of isolation of respiratory infection by non-tuberculous mycobacteria (NTM) and to analyze the clinical-epidemiological characteristics of patients infected with NTM. METHODS: Retrospective observational study of 83 respiratory samples with NTM isolation from 62 patients between 2015 and 2021 at the Doctor Balmis General University Hospital. RESULTS: MNT respiratory infection criteria were met in 15 patients (24.2%). The most frequently isolated NTM's in patients who met infection criteria were those belonging to the Mycobacterium avium complex. Of the 15 infected patients, 11 (73.3%) had respiratory comorbidity and the most frequent respiratory comorbidity in infected patients was bronchiectasis (5 patients; 45.5%). Of the infected patients, targeted antibiotic treatment was prescribed in 83.3% of the cases. CONCLUSION: One in 7 patients with NTM isolation meets infection criteria. The main role of the species of Mycobacterium avium complex is corroborated, and the relevance of lung structural damage in the development of lung disease due to NTM.


Assuntos
Bronquiectasia , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Pneumonia Bacteriana , Infecções Respiratórias , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas , Complexo Mycobacterium avium , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia
7.
Microb Pathog ; 178: 106062, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36914054

RESUMO

The human microbiome is a complex ecosystem that mediates interaction between the human host and the environment. All of the human body is colonized by microorganisms. The lung as an organ used to be considered sterile. Recently, however, there has been a growing number of reports with evidence that the lungs are also in a state of carrying bacteria. The pulmonary microbiome is associated with many lung diseases and is increasingly reported in current studies. These include; chronic obstructive pulmonary disease (COPD), asthma, acute chronic respiratory infections, and cancers. These lung diseases are associated with reduced diversity and dysbiosis. It directly or indirectly affects the occurrence and development of lung cancer. Very few microbes directly cause cancer, while many are complicit in cancer growth, usually working through the host's immune system. This review focuses on the correlation between lung microbiota and lung cancer, and investigates the mechanism of action of lung microorganisms on lung cancer, which will provide new and reliable treatments and diagnosis of lung cancer in the future.


Assuntos
Pneumopatias , Neoplasias Pulmonares , Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão/microbiologia , Pneumopatias/microbiologia , Disbiose
8.
J Infect Chemother ; 29(6): 628-630, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36894014

RESUMO

Nontuberculous mycobacteria (NTM) are environmental bacteria resistant to many common disinfectants and ultraviolet radiation. Inhalation of aerosols generated from NTM-containing water and soil causes NTM lung disease, especially in people with underlying lung diseases and decreased immunity. To prevent healthcare-acquired NTM infections, it is important to eradicate NTM living in hospital environments. Therefore, we evaluated the efficacy of gaseous ozone for the inactivation of NTM, namely Mycobacterium (M.) avium, M. intracellulare, M. kansasii, M. abscessus subsp. abscessus and M.abscessus subsp. massiliense. Gaseous ozone treatment at 1 ppm for 3 h reduced the bacterial number of all strains by more than 97%. Gaseous ozone treatment could be a practical, effective and convenient disinfection method for NTM living in hospital environments.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Raios Ultravioleta , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pneumopatias/microbiologia , Hospitais
9.
Ann Clin Microbiol Antimicrob ; 22(1): 14, 2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36800956

RESUMO

Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils' capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections.


Assuntos
Bronquiectasia , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas/fisiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Neutrófilos , Pneumopatias/complicações , Pneumopatias/microbiologia , Bronquiectasia/complicações , Bronquiectasia/microbiologia
11.
J Infect Chemother ; 29(1): 82-86, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36162647

RESUMO

An 81-year-old man was admitted to our hospital because of fever and malaise that had persisted for 3 months. The patient had undergone two aortic valve replacements, 10 and 5 years previously, because of aortic valve regurgitation and infectious endocarditis. He also had had asymptomatic Mycobacterium abscessus complex (MABC) pulmonary disease for the two previous years. Contrast-enhanced computed tomography showed a mediastinal abscess and an ascending aortic aneurysm. Mycobacterium abscessus subsp. massiliense was cultured from his blood, suggesting the aortic aneurysm was secondary to infection of an implanted device. After enlargement over only a few days, a leakage of contrast medium to the mediastinal abscess was found on computed tomography. The patient was diagnosed with rupture of an infectious aortic aneurysm, and emergency aortic replacement and drainage of the mediastinal abscess were successful. The patient was treated with several antibiotics, including meropenem, amikacin, and clarithromycin, and his general condition improved. Cultures from both the mediastinal abscess and a pericardial patch that was placed at the time of surgery 5 years previously revealed MABC. In our case, the infected aortic aneurysm most likely resulted from MABC pulmonary disease rather than from previous intraoperative contamination. This route of infection is rare. Physicians should be aware of the possibility of dissemination and subsequent infection of implants related to MABC pulmonary disease.


Assuntos
Aneurisma Aórtico , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Masculino , Humanos , Idoso de 80 Anos ou mais , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Abscesso , Claritromicina/uso terapêutico , Antibacterianos/uso terapêutico , Pneumopatias/microbiologia , Testes de Sensibilidade Microbiana
12.
Phytomedicine ; 108: 154475, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36252465

RESUMO

BACKGROUND: Opioids are widely used in clinical practice. However, their long-term administration causes respiratory depression, addiction, tolerance, and severe immunosuppression. Traditional Chinese medicine (TCM) can alleviate opioid-induced adverse effects. Compound 511 is particularly developed for treating opioid addiction, based on Jiumi Liangfang, an ancient Chinese drug treatment and rehabilitation monograph completed in 1833 A.D. It is an herbal formula containing eight plants, each of them contributing to the overall pharmacological effect of the product: Panax ginseng C. A. Meyer (8.8%), Astragalus membranaceus (Fisch.) (18.2%), Datura metel Linn. (10.95%), Corydalis yanhusuo W. T. Wang (14.6%), Acanthopanar gracilistµlus W. W. Smith (10.95%), Ophiopogon japonicus (Linn. f.) Ker-Gawl. (10.95%), Gynostemma pentaphyllum (Thunb.) Makino (10.95%), Polygala arvensis Willd. (14.6%). This formula effectively ameliorates opioid-induced immunosuppression. However, the underlying mechanism remains unclear. PURPOSE: To reveal the effects of Compound 511 on the immune response of morphine-induced immunosuppressive mice and their potential underlying molecular mechanism. This study provides information for a better clinical approach and scientific use of opioids. METHODS: Immunosuppression was induced in mice by repeated morphine administration. Th1/Th2/Th17/Treg cell levels were measured using flow cytometry. Splenic transcription factors of Th1/Th2/Th17/Treg and outputs of the regulatory PI3K/AKT/mTOR signaling pathway were determined. Subsequently, methicillin-resistant Staphylococcus aureus (MRSA) was administered intranasally to morphine-induced immunosuppressive mice pretreated with Compound 511. Their lung inflammatory status was assessed using micro-computer tomography (CT), hematoxylin and eosin (H&E) staining, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to morphine, Compound 511 significantly decreased the immune organ indexes of mice, corrected the Th1/Th2 and Treg/Th17 imbalance in the immune organs and peripheral blood, reduced the mRNA levels of FOXP3 and GATA3, and increased those of STAT3 and T-bet in the spleen. It improved immune function and reduced MRSA-induced lung inflammation. CONCLUSION: Compound 511 ameliorates opioid-induced immunosuppression by regulating the balance of Th1/Th2 and Th17/Treg via PI3K/AKT/mTOR signaling pathway. Thus, it effectively reduces susceptibility of morphine-induced immunosuppressive mice to MRSA infection.


Assuntos
Medicamentos de Ervas Chinesas , Pneumopatias , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Analgésicos Opioides/farmacologia , Terapia de Imunossupressão , Morfina/farmacologia , Morfina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T Reguladores , Células Th17 , Serina-Treonina Quinases TOR/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico
13.
Front Public Health ; 10: 912651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979468

RESUMO

According to the existing data, the incidence and prevalence of non-tuberculous mycobacteria (NTM) are increasing worldwide. The risk factors and mental health status of patients with NTM lung disease are important and deserve our attention. A total of 180 patients with NTM lung disease hospitalized from January 2018 to December 2021 were selected as the NTM group, and 90 patients with non-severe community-acquired pneumonia (CAP) who were hospitalized during the same period were selected as the control group. The Symptom Checklist-90 (SCL-90) was used to assess the mental health status of the patients. The data were analyzed using descriptive statistics, logistic regression, and receiver operating characteristic (ROC) curves. There were no significant differences in age, sex, marital status, or smoking history between the two groups (p > 0.05), but there were significant differences in educational level, underlying diseases, occupation, living environment, and body mass index (BMI) (p < 0.01). According to the classification of basic diseases, bronchiectasis was found in 82 (45.6%) patients, followed by hypertension in 66 (36.7%) patients, and chronic obstructive pulmonary disease (COPD) in 39 (21.7%) patients. The NTM strains were identified M. intercelleulare caused 41 cases (22.8%), followed by Mycobacterium avium and Mycobacterium gordonae, each with 35 cases (19.4%), and Mycobacterium abscessus with 32 cases (17.8%). The SCL-90 found that 160 (88.9%) of 180 patients with NTM lung disease had developed mental health problems, among which the four highest-scoring factors were anxiety (ANX: 29.4%), depression (DEPR: 18.8%), sleep and diet (SD: 16.9%), and somatization (SOM: 11.3%). Through multivariate logistic regression analysis, it was found that educational level, underlying diseases, living environment, and BMI were independent risk factors for the occurrence of NTM lung disease (p < 0.01). The Hosmer-Lemeshow test was used to check the model's fitness. The ROC curve showed that the area under the curve (AUC) was 0.896, the sensitivity was 83.3%, and the specificity was 85.6%. Patients with NTM lung disease have many risk factors and prominent mental health problems that may require interventions during the process of clinical diagnosis and treatment.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Nível de Saúde , Humanos , Pneumopatias/complicações , Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Estudos Retrospectivos , Fatores de Risco
14.
Antimicrob Agents Chemother ; 66(9): e0226121, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35950842

RESUMO

We investigated the treatment outcomes of patients with cavitary nodular bronchiectatic (C-NB)-type Mycobacterium avium complex (MAC) pulmonary disease (PD) via outcome comparisons between the fibrocavitary (FC) and C-NB types treated with guideline-based therapy (GBT) composed of daily three-drug oral antibiotics and injectable aminoglycoside. Additionally, we analyzed whether treatment with oral antibiotics alone would result in acceptable outcomes for the C-NB type. From 2002 to 2019, patients with cavitary MAC-PD who received three-drug oral antibiotics with or without an injectable aminoglycoside for ≥1 year were retrospectively enrolled at a tertiary referral center in South Korea. We compared the rates of culture conversion at 12 months according to the radiological type and treatment regimen. The overall culture conversion rate at 12 months of 154 patients with cavitary MAC-PD who received GBT was 75.3%. Among them, the culture conversion rates of 114 patients with the C-NB type were higher than that of 40 patients with the FC-type (80.7% versus 60.0%, respectively; P = 0.009). Of 166 patients with the C-NB-type treated with oral medications with or without an injectable drug, 83.7% achieved culture conversion at 12 months. The conversion rates of those who received oral medications alone and those treated with oral medications and an injectable aminoglycoside were similar (90.4% versus 80.7%, respectively; P = 0.117). In conclusion, the culture conversion rates of the patients with C-NB type treated with GBT were significantly higher than those of patients with the FC type. Additionally, the C-NB type could be treated with oral medications alone.


Assuntos
Bronquiectasia , Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Humanos , Pneumopatias/microbiologia , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/diagnóstico por imagem , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Microbiol Spectr ; 10(3): e0045122, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35579455

RESUMO

The establishment of animal models reflecting human Mycobacterium avium complex (MAC) lung disease (LD) pathology has the potential to expand our understanding of the disease pathophysiology. However, inducing sustained infection in immunocompetent mice is difficult since MAC generally shows less virulence and higher genetic variability than M. tuberculosis. To overcome this hurdle, we developed a screening system for identifying virulent MAC strains using whole-genome sequencing (WGS). We obtained nine clinical strains from Mycobacterium avium complex lung disease (MAC-LD) patients and divided them into two groups to make the mixed strain inocula for infection. Intranasal infection with the strain mixture of both groups in BALB/c mice resulted in progressive infection and extensive granuloma formation in the lungs, suggesting the existence of highly pathogenic strains in each group. We hypothesized that the change in the abundance of strain-specific single-nucleotide variants (SNVs) reflects the change in bacterial number of each strain in infected lungs. Based on this hypothesis, we quantified individual strain-specific SNVs in bacterial DNA from infected lungs. Specific SNVs for four strains were detected, suggesting the pathogenicity of these four strains. Consistent with these results, individual infection with these four strains induced a high lung bacterial burden, forming extensive peribronchial granuloma, while the other strains showed a decreased lung bacterial burden. The current method combining mixed infection and WGS accurately identified virulent strains that induced sustained infection in mice. This method will contribute to the establishment of mouse models that reflect human MAC-LD and lead to antimycobacterial drug testing. IMPORTANCE To promote research on Mycobacterium avium complex (MAC) pathogenicity, animal models reflecting human progressive MAC lung disease (MAC-LD) are needed. Because there is high genetic and virulence diversity among clinical MAC strains, choosing a suitable strain is an important process for developing a mouse model. In this study, we developed a screening system for virulent strains in mice by combining mixed infection and whole-genome sequencing analysis. This approach is designed on the hypothesis that in vivo virulence of MAC strains can be examined simultaneously by comparing changes in the abundance of strain-specific single-nucleotide variants in the mouse lungs after infection with mixed strains. The identified strains were shown to induce high bacterial burdens and cause extensive peribronchial granuloma resembling the pulmonary pathology of human MAC-LD. The current method will help researchers develop mouse models that reflect human MAC-LD and will lead to further investigation of MAC pathogenicity.


Assuntos
Coinfecção , Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Mycobacterium tuberculosis , Animais , Pneumopatias/microbiologia , Camundongos , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/microbiologia , Mycobacterium tuberculosis/genética , Nucleotídeos
18.
Expert Rev Respir Med ; 16(4): 469-475, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35245168

RESUMO

BACKGROUND: Patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) have impaired exercise capacity, but the underlying factors are unknown. We investigated the characteristics of patients with NTM-PD and impaired exercise capacity. METHODS: In total, 149 patients with NTM-PD participated in this study. Patients completed the incremental shuttle walk test (ISWT) to assess exercise capacity. Peripheral muscle strength and pulmonary function were also assessed. Radiological findings were classified into three phenotypes: non-cavitary nodular bronchiectatic (NC-NB) form, cavitary nodular bronchiectatic form, and fibrocavitary (FC) form. RESULTS: The median ISWT distance (ISWD) and %ISWD were 450 meters and 88%. Participants were classified into three groups according to %ISWD, with %ISWD <60% as the severely decreased group, 60%-80% as the moderately decreased group, and >80% as the normal or mildly decreased group. In a comparison of %ISWD among phenotypes, FC form had significantly lower %ISWD than those with NC-NB form. In the severely decreased group, peripheral muscle strength and pulmonary function were significantly lower than the other two groups. From a radiological standpoint, significantly more patients had FC form in the group with severely decreased %ISWD. CONCLUSIONS: Decreased ISWD is characterized by a deterioration in physical function and the presence of FC lesions in NTM-PD.


Assuntos
Bronquiectasia , Pneumopatias , Humanos , Pneumopatias/microbiologia , Força Muscular , Micobactérias não Tuberculosas , Teste de Caminhada
19.
Clin Infect Dis ; 75(8): 1397-1404, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-35165686

RESUMO

BACKGROUND: There are conflicting results regarding endogenous estrogen exposure and risk of incident nontuberculous mycobacterial pulmonary disease (NTM-PD). In addition, evidence on impact of hormone replacement therapy (HRT) on risk of NTM-PD is lacking. This study aimed to evaluate the impacts of endogenous estrogen exposure and HRT on risk of NTM-PD in postmenopausal women. METHODS: This population-based cohort study comprised 1 400 095 postmenopausal women without previous NTM-PD who participated in the 2009 national health screening exam in South Korea. The cohort was followed until the date of incident NTM-PD, death, or December 2018. We evaluated whether lifetime endogenous estrogen exposure and HRT were associated with incident NTM-PD. Endogenous estrogen exposure was evaluated using age at menarche and menopause and reproductive period (duration between age at menarche and age at menopause). RESULTS: During a median of 8.4 (interquartile range, 8.2-8.7) years of follow-up, 0.1% of participants (1818/1 400 095) developed NTM-PD, with an incidence rate of 0.15/1000 person-years. Multivariable Cox regression analyses showed no significant relationship between endogenous estrogen exposure (age at menarche, age at menopause, and reproductive period) and risk of NTM-PD. In contrast, duration of HRT showed a significant dose-response relationship with incident NTM-PD even after adjustment for demographics and reproductive factors (adjusted hazard ratio [95% CI]: 1.30 [1.12-1.51] in HRT for <2 years; 1.28 [1.03-1.59] in 2-5 years; and 1.65 [1.33-2.05] in ≥5 years). CONCLUSIONS: While there was no significant association with endogenous estrogen exposure, HRT was monotonically associated with increased risk of NTM-PD in postmenopausal women.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Estudos de Coortes , Estrogênios/efeitos adversos , Feminino , Humanos , Incidência , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pós-Menopausa , República da Coreia/epidemiologia , Fatores de Risco
20.
Int J Tuberc Lung Dis ; 26(1): 50-56, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969429

RESUMO

BACKGROUND: The surgical treatment for non-tuberculous mycobacterial pulmonary disease (NTM-PD) has an important adjunctive role and reported outcomes have been generally good; however, the prognostic factors remain unclear.METHODS: Sixty-one patients with NTM-PD who underwent surgical resection for a therapeutic purpose from January 2000 to March 2017 at five affiliated institutions were enrolled. We explored the factors that influence complications and prognosis by retrospectively referring to the medical records.RESULTS: The mean age of the present cohort was 61.8 ± 11.4 years. The pathogen was Mycobacterium avium complex in 49 patients, M. abscessus in 5. The most common indications were refractory to medication in 39. The surgical techniques employed were lobectomy or further resection in 49, sublobar resection in 8, with video-assisted thoracoscopic surgery in 21. Sputum culture conversion rate was 95.1%. Univariate analysis of factors associated with deterioration revealed significant differences related to age (P = 0.025), pre-operative albumin level (P = 0.001) and development of postoperative complications (P = 0.037), while pre-operative albumin level alone was a significant factor in multivariate analysis (P = 0.009).CONCLUSION: Outcomes after resection were generally good in the present cases. Nutritional status, as indicated by albumin level, may affect prognosis after surgical treatment.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Idoso , Humanos , Pneumopatias/microbiologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Prognóstico , Estudos Retrospectivos
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