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Background: The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied. Methods: Patients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression. Results: Among enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells. Conclusions: In patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment. [ABSTRACT FROM AUTHOR]

Incidentally discovered solitary pulmonary nodules (SPN) caused by nontuberculous mycobacteria (NTM) is uncommon, and its optimal treatment strategy remains uncertain. This cohort study determined the clinical characteristics and outcome of asymptomatic patients with NTM-SPN after surgical resection. Resected SPNs with culture-positive for NTM in six hospitals in Taiwan during January, 2010 to January, 2017 were identified. Asymptomatic patients without a history of NTM-pulmonary disease (PD) or same NTM species isolated from the respiratory samples were selected. All were followed until May 1, 2019. A total of 43 patients with NTM-SPN were enrolled. Mycobacterium avium complex (60%) and M. kansasii (19%) were the most common species. The mean age was 61.7 ± 13.4. Of them, 60% were female and 4% had history of pulmonary tuberculosis. The NTM-SPN was removed by wedge resection in 38 (88%), lobectomy in 3 (7%) and segmentectomy in 2 (5%). Caseating granuloma was the most common histologic feature (58%), while chronic inflammation accounts for 23%. Mean duration of the follow-up was 5.2 ± 2.8 years (median: 4.2 years [2.5–7.0]), there were no mycobacteriology recurrence or NTM-PD development. In conclusion, surgical resection is likely to curative for incidentally discovered NTM-SPN in asymptomatic patients without culture evidence of the same NTM species from respiratory specimens, and routine mycobacterium culture for resected SPN might be necessary for differentiating pulmonary tuberculosis and NTM because further treatment differs. [ABSTRACT FROM AUTHOR]

Background/purpose: Mycobacterium avium complex (MAC) is frequently considered to be a contaminant or transient colonizer. To the best of our knowledge, there have been very few reports regarding the clinical significance of MAC isolates in respiratory specimens, and the associated disease spectrum in Taiwan. The purpose of this study was to investigate the clinical significance of MAC isolates in respiratory specimens.Methods: We retrospectively reviewed the medical records of patients in a medical center in Southern Taiwan from whom MAC isolates were recovered from respiratory specimens, and analyzed their clinical features, chest imaging findings, treatment and prognosis. We also performed an antibiotic susceptibility test on our MAC isolates.Results: The 64 isolates used in this study were recovered from April to October 2001 from respiratory specimens in 54 patients admitted to Kaohsiung Veterans General Hospital, Taiwan. According to the 2007 criteria of the American Thoracic Society, a total of 12 patients (22.2%) had clinically significant MAC pulmonary disease.Conclusion: Despite the increased frequency of recovering MAC from respiratory specimens, most cases did not meet the criteria of American Thoracic Society for clinically significant nontuberculous pulmonary disease. The minimum inhibitory concentrations of drugs against these MAC isolates might help to guide treatment, but further studies should be done. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 627–630 The clinical characteristics and outcomes of 71 patients with mycobacterial bacteraemia, infected with human immunodeficiency virus (HIV) ( n = 47) and not infected with HIV ( n = 24) are described. Mycobacterium avium complex (MAC) (54.9%) constituted the most frequently isolated mycobacterium, followed by Mycobacterium tuberculosis (MTB) (38.0%), Mycobacterium kansasii (4.2%), and Mycobacterium abscessus (2.8%). The Beijing family genotype was the most common type in MTB, and Mycobacterium intracellulare was the most common species in MAC. The overall mortality rate was 33.8%; it was lower in HIV-infected than in non-HIV-infected patients. HIV-infected patients were younger, had fewer underlying diseases and better nutritional status, and were more likely to have MAC bacteraemia than MTB bacteraemia. [ABSTRACT FROM AUTHOR]

Purpose: Mycobacterium avium complex-lung disease (MAC-LD) is increasing worldwide and may progress to cause mortality significantly. However, for patients without initial treatment at diagnosis, the survival outcomes and predictors of mortality remain unclear., Methods: From 2011 to 2017, MAC-LD patients at two medical centers in Taiwan were screened, and those who received MAC treatment at the initial were excluded. The clinical course and characteristics were recorded. Cox regression analysis and receiver operating characteristic (ROC) curves were performed to assess risk factors of mortality within 4 years., Results: We included 123 MAC-LD patients without initial MAC treatment. The mean follow-up period was 4.15 ± 2.52 years. Twenty-two (17.9%) patients died within four years. Multivariate analysis showed that four independent factors related to 4-year mortality were consolidation pattern (hazard ratio [HR] 6.0, 95% confidence interval [2.3-15.5]), radiographic score > 6 (HR:11.0 [4.0-31.1]), radiographic deterioration within two years (HR: 5.2 [2.1-13.1]) and no MAC treatment during follow up (HR: 6.5 [1.3-31.1]). The areas under the ROC curves for prediction of 4-year mortality for the combination of consolidation and radiographic score >6, the two factors plus radiographic progression, the two plus no MAC treatment, and the combination of the four factors were 0.702, 0.798, 0.758, and 0.835, respectively., Conclusions: The four-year mortality rate in MAC-LD without initial treatment is high. Presence of consolidation pattern and radiographic score >6 at initial visit, radiographic deterioration and no treatment during follow-up were risk factors of 4-year mortality in initially untreated MAC-LD., (Copyright © 2020. Published by Elsevier Ltd.)

BACKGROUND: Disseminated Mycobacterium avium complex infection (DMAC) has symptoms and microscopic findings similar to those of TB in HIV patients. To inform a clinical algorithm-based differential diagnosis, we aimed to characterise the clinical features of DMAC. METHODS: This was a retrospective cohort study of 192 HIV-positive patients with culture-confirmed mycobacterial infections hospitalised during 1996-2016 at a major HIV/AIDS treatment centre in Taiwan. RESULTS: HIV patients with DMAC ( n = 58) had a three times higher 1-year mortality than those with TB ( n = 98) (48.3% vs. 16.3%, P < 0.001). DMAC and TB were not distinguishable by the WHO TB screening criteria (fever, cough, night sweats or weight loss). Nevertheless, DMAC was characterised by a lower median CD4 count (5.0 cells/µL vs. 38.5 cells/µL, P < 0.001), lower median body mass index (BMI) (17.7 kg/m² vs. 19.7 kg/m², P = 0.002) and the absence of chest radiographic findings ( P < 0.001). Simultaneous presence of CD4 <20 cells/µl, BMI <18.5 kg/m² and negative chest radiographic finding had a 98% specificity for diagnosing DMAC against TB or other types of mycobacterial infections. CONCLUSION: DMAC is an important differential diagnosis of TB in HIV patients. A simple rule based on CD4, BMI and chest radiography may inform the decision to start anti-DMAC treatment in patients with mycobacterial infection.

Nontuberculous mycobacteria (NTM) are critical emerging global infectious pathogens. Though NTM can be mere colonizers when isolated from human specimens, NTM are also responsible for diverse human infections. NTM-lung disease (NTM-LD) is the most common human disease entity. The present review aims to provide general insight into NTM-LD epidemiology in Taiwan. In reviewing NTM epidemiology in Taiwan, we discovered three distinguishing features. First, NTM disease incidence has increased in Taiwan over the past decade. Second, the distribution of NTM varies geographically in Taiwan. Mycobacterium avium-intracellulare complex (MAC) is the dominant species in northern Taiwan, whereas Mycobacterium abscessus complex and MAC may be equally dominant in southern Taiwan. Third, researchers in Taiwan have published valuable research investigating NTM among special patient populations, including patients in intensive care units, with ventilator dependency, with pulmonary tuberculosis, and who are infected with specific NTM species. The largest obstacle to clarifying NTM epidemiology in Taiwan may be the lack of routine NTM species identification in laboratories. Increased awareness of NTM diseases and acknowledgment that NTM species identification is crucial and guides clinical management are essential steps for facilitating the identification of NTM species in laboratories., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Advanced molecular typing methods have greatly expanded the taxonomy of Mycobacterium avium complex (MAC) species; however, little is known about the epidemiology and clinical features of bacteraemia caused by different MAC species. In this study, the clinical characteristics of patients treated for MAC bacteraemia in a tertiary-care centre in northern Taiwan during 2008-2014 were investigated. Isolates were identified to species level by rpoB gene and 16S-23S rRNA internal transcribed spacer region sequencing. Among 30 patients with bacteraemia due to MAC, the majority (n = 26) had concomitant human immunodeficiency virus (HIV) infection. Of the 30 blood isolates obtained from patients, 24 were M. avium subsp. hominissuis, 4 were Mycobacterium colombiense and 2 were Mycobacterium intracellulare. All four M. colombiense isolates were from HIV-infected patients. Bacteraemia due to M. colombiense was associated with higher 30-day mortality than bacteraemia due to M. avium subsp. hominissuis [2/4 (50%) vs. 1/24 (4%); P = 0.045, Fisher's exact test]. All four M. colombiense isolates were susceptible to clarithromycin, moxifloxacin and linezolid. Among the five patients who received ethambutol treatment and four patients who received fluoroquinolone treatment for various durations between positive MAC cultures, two and three patients, respectively, had isolates with significantly increased (≥4-fold) ethambutol and fluoroquinolone minimum inhibitory concentrations. M. colombiense was the second leading causative pathogen of MAC bacteraemia, comprising 15% of all MAC isolates obtained from HIV-positive patients. Monitoring the susceptibility of MAC isolates to ethambutol and fluoroquinolones is warranted in patients with persistent MAC bacteraemia., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients., Design: Prospective cohort study., Setting: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan., Methods: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens., Results: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60)., Conclusion: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.