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Background: The incidence of nontuberculous mycobacterial (NTM) pulmonary disease caused by Mycobacterium avium complex (MAC) in apparently immune-competent people is increasing worldwide. We performed a systematic review of the published literature on five-year all-cause mortality in patients with MAC lung disease, and pooled the mortality rates to give an overall estimate of five-year mortality from these studies., Methods: We systematically reviewed the literature up to 1st August 2017 using PubMed® and ProQuest Dialog™ to search Medline® and Embase® databases, respectively. Eligible studies contained > 10 patients with MAC, and numerical five-year mortality data or a treatment evaluation for this patient group. Mortality data were extracted and analysed to determine a pooled estimate of all-cause mortality., Results: Fourteen of 1035 identified studies, comprising 17 data sets with data from a total of 9035 patients, were eligible. The pooled estimate of five-year all-cause mortality was 27% (95% CI 21.3-37.8%). A high degree of heterogeneity was observed (I 2  = 96%). The mortality in the data sets varied between 10 and 48%. Studies predominantly including patients with cavitary disease or greater comorbidity reported a higher risk of death. Patients in Asian studies tended to have a lower mortality risk. Predictors of mortality consistent across studies included male sex, presence of comorbidities and advanced patient age., Conclusions: Despite high heterogeneity, most studies in patients with MAC pulmonary disease document a five-year all-cause mortality exceeding 25%, indicating poor prognosis. These findings emphasise the need for more effective management and additional prospective mortality data collection.

Background: In multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review., Methods: The study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients., Results: All 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3 months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2 μg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy., Conclusions: Inhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.

Background: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival., Methods: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2., Results: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m 2 , lymphocyte count <1000 cells/μL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2., Conclusions: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

Background: The incidence of nontuberculous mycobacteria (NTM) infections is increasing worldwide, however formal evaluations of the epidemiology of NTM infections are limited. Understanding the trends and true prevalence of NTM is a major priority for optimizing infection control programmes and resources. The purpose of this study was to investigate the epidemiology, clinical manifestations, and radiologic findings in NTM-infected patients at specialized Tuberculosis (Tb) treatment centre in South Korea, which is endemic to Tb, and find solutions to control NTM infections., Methods: A retrospective descriptive study was conducted among patients who were diagnosed with NTM from November 2011 to January 2016 at Seoul Metropolitan Government Seobuk hospital, Korea, using medical records and chest radiography results. Prevalence of NTM using national health insurance data was compared to the prevalence and incidence of Tb using National statistics data., Results: The age- and sex- adjusted prevalence of NTM infection per 100,000 population increased between 2009 (9.4) and 2016 (36.1). However, the prevalence and incidence of Tb per 100,000 population decreased from 106.5 to 74.4, and 81.2 to 61.8, respectively. In total, 64 patients (37 [57.8%] men) were enrolled in the study. Among 33 (51.6%) patients with slowly growing nontuberculous mycobacteria (SGM) infection, 29 were detected with Mycobacterium avium complex (n = 13, M. avium; n = 16, M. intracellulare), and 4 with M. kansasii. Among 31 (48.4%) patients with rapidly growing nontuberculous mycobacteria (RGM) infection, 27 and 4 patients were detected with M. abscessus complex and M. fortuitum complex, respectively. RGM patients were more likely to have current Tb (P = 0.041), cough (P < 0.05), and sputum (P < 0.01) than SGM patients in the univariate analysis, but not in the multivariate analysis., Conclusion: Given the increasing prevalence of NTM infections, precise epidemiological and surveillance data should be obtained by reporting NTM infections to public health authorities. Introducing nucleic acid amplification tests to differentiate between Tb and NTM in smear-positive specimens should be considered.

Background: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level., Methods: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included., Results: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old., Conclusion: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required.