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Background: Epidemiological trends and clinical relevance of NTM species in Japan following the adoption of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry remain unclear., Methods: We analyzed the results of mycobacterial culture tests of respiratory specimens collected between January 2017 and December 2021. We assessed the clinical relevance of NTM species by analyzing the proportion of patients diagnosed with NTM pulmonary infection (NTM-PI). We illustrated the incidence and clinical relevance of each NTM species using a two-dimensional scatter plot. Medical chart review and radiological analysis were also performed for less common species., Results: Among 65,368 respiratory specimens tested for acid-fast bacilli, NTM were identified in 12,802 specimens from 3177 patients. The number of incident cases with NTM-PI has continued to increase. Notably, the number of incident cases with M. abscessus species (MABS) was continuously increasing and accounted for 10.6% of all incident cases with NTM-PI. The clinical relevance of the common NTM species, M. avium complex, MABS and M. kansasii, ranged from 57 to 72%. Seven other species exhibited a higher clinical relevance than these common NTM species, with M. shinjukuense (100%) having the highest clinical relevance. On the other hand, 11 species, including M. fortuitum (32.4%), M. xenopi (20.0%), and M. gordonae (22.9%), showed clinical relevance below 50%., Conclusions: The present study clarified the incidence and clinical relevance of NTM species using a two-dimensional scatter plot, which could serve as a useful tool for clinical decision-making and future epidemiological research., Competing Interests: Declaration of competing interest Kozo Morimoto received an honorarium for consulting fees and an educational lecture from Insmed G.K. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that cause chronic lung disease. Rates of NTM pulmonary disease (NTM PD) have increased over the last several decades, yet national estimates in the United States (US) have not been assessed since 2015., Methods: We used a nationally representative population of Medicare beneficiaries aged ≥ 65 years to assess rates of NTM PD in a high-risk population from 2010 to 2019. Poisson generalized linear models were used to assess the annual percent change in incidence in the overall population and among key demographic groups such as sex, geography, and race/ethnicity. We evaluated the relative prevalence of various comorbid conditions previously found to be associated with NTM PD., Results: We identified 59,724 cases of incident NTM PD from 2010 to 2019 from an annual mean population of 29,687,097 beneficiaries, with an average annual incidence of 20.1 per 100,000 population. NTM PD incidence was overall highest in the South and among women, Asian individuals, and persons aged ≥ 80 years relative to other studied demographic groups. The annual percent change in NTM PD incidence was highest in the Northeast, at 6.5%, and Midwest, at 5.9%, and among women, at 6.5%. Several comorbid conditions were highly associated with concurrent NTM diagnosis, including allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis., Conclusions: Here we provide current estimates of NTM PD incidence and prevalence and describe increasing trends in the US from 2010 to 2019. Our study suggests a need for improved healthcare planning to handle an increased future caseload, as well as improved diagnostics and therapeutics to better detect and treat NTM PD in populations aged ≥ 65 years., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Nontuberculous mycobacteria (NTM) prevalence in water systems has raised concerns about Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD). Understanding the relationship between NTM-PD, drinking water distribution systems (DWDS), and other epidemiological factors is crucial for public health., Methods: A case-control study was conducted at the Inpatient Department of Tuberculosis Department of Shanghai Pulmonary Hospital. Subjects were divided into the NTM-PD group (n = 314) and pulmonary tuberculosis (PTB) group (n = 308) at a 1:1 ratio. Data was collected through questionnaires covering general information, depression (Self-Rating Depression Scale, SDS), and anxiety (Self-Rating Anxiety Scale, SAS). Multivariate unconditional logistic regression analysis was employed for the study., Results: The average age of NTM-PD patients was 55.26±14.44, with clinical symptoms including chest tightness, shortness of breath, hemoptysis, fever, and expectoration. Risk factors for NTM-PD included age (>60 years old, OR=1.042), gender (female, OR = 3.089), secondary water supply system (OR = 7.813), occupation (farmer/flower farmer, OR=2.676), depression (OR = 2.956), recurrent bronchiectasis (OR = 6.314), chronic obstructive pulmonary disease (COPD, OR = 2.704), and autoimmune disease (OR = 13.588) (P < .05). Use of household water purifiers was identified as a protective factor (OR = 0.128, P < .001)., Conclusion: DWDS, drinking water mode, soil-related occupation, bronchiectasis, COPD, age, sex, and depression were closely related to the risk of NTM-PD. It is suggested to pay attention to water hygiene and illness progress and regulate mood to prevent NTM-PD in daily life.

Background: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy., Research Question: What is the rate of NTM-PD progression, and what are the predictors of progression?, Study Design and Methods: Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed., Results: Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV 1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression., Interpretation: About one-half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely., Trial Registry: ClinicalTrials.gov; No.: NCT01616745; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US $5,044 (interquartile range US $3,586-$9,680) over 49.7 months (interquartile range 33.0-68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Introduction: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui., Methodology: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens., Results: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found., Conclusions: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Zhaoyu Zha, Long Gao, Dongping Wang, Dongfang Xu, Yanyan Liu, Yi Liu, Shengsheng Liu, Jiabin Li, Wenhong Lin.)

Nontuberculous mycobacteria (NTM) pulmonary disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The existence of host susceptibility to NTM infection has been recognized from a high incidence among Asians compared to other populations in the United States, a high incidence among slender, middle-aged women, and the presence of familial clusters. Recent whole exome sequencing and genome-wide association studies have identified immune, CFTR, cilia, connective tissue and ion homeostasis genes as host susceptibility genes. Large-scale international collaborative studies and functional analyses are expected to elucidate host susceptibility in the future., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium avium. Single-center studies also support increasing trends as well as a persistent burden of undiagnosed NTM among persons suspected of having tuberculosis (TB), in countries with moderate-to-high TB prevalence. Cumulative exposure to water and soil presents an increased risk to susceptible hosts, and trace metals in water supply are recently recognized risk factors. Establishing standard case definitions for subnational and national surveillance systems with mandatory notification of NTM-PD are needed to allow comparisons within and across countries and regions., (Published by Elsevier Inc.)

Objective: The objective of this study is to analyze the risk factors associated with bronchiectasis combined with non-tuberculous mycobacteria pulmonary disease(NTM-PD) and provide a basis for more effective prevention and treatment strategies., Methods: The study subjects for this manuscript were patients with bronchiectasis who were admitted to the infection department between January 2021 and June 2023.There were 34 patients with NTM-PD in the observation group, and 52 patients with simple bronchiectasis in the control group. Basic information, imaging features, serum albumin levels, and infection indicators were collected from both groups of patients.Univariate and multivariate logistic regression analysis were performed to analyze the risk factors for NTM-PD in patients with bronchiectasis., Results: Multivariate logistic regression analysis revealed that bronchiectasis exacerbation occurring at least twice a year(OR = 3.884, 95% CI: 1.200-12.568), involvement of three or more lung lobes with bronchiectasis (OR = 3.932, 95% CI: 1.208-12.800), hypoalbuminemia (OR = 3.221, 95% CI: 1.015-10.219), and the NLR index (OR = 1.595, 95% CI: 1.200-2.119) were significant risk factors for non-tuberculous mycobacteria pulmonary disease in individuals with bronchiectasis (P < 0.05)., Conclusion: Patients with bronchiectasis accompanied by NTM-PD present specific risk factors that should be promptly addressed through prevention and treatment., (© 2023. The Author(s).)

Background: Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance., Methods: The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review., Results: Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure., Conclusions: Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions., Competing Interests: Potential conflicts of interest. EIP site coauthors' institutions received funding from the CDC. E. H. reports receipt of consulting fees and serving on advisory boards for AN2 Therapeutics and the MannKind Corporation. K. L. W. reports receipt of grants or contracts and consulting fees from Insmed, Paratek, Red Hill Biopharma, AN2 Therapeutics, Renovion, and Spero and participation on a data and safety monitoring board or advisory board for Red Hill Biopharma. R. L. reports service on the program committee for IDWeek and receipt of travel support for conference planning and for the conference; service as associate editor for the American Academy of Pediatrics (AAP) Red Book; receipt of fees for editorial work that were donated to the Minnesota Department of Health; receipt of support to attend the AAP Committee on Infectious Disease meetings; service on the Council of State and Territorial Epidemiologists (CSTE) Executive Board and receipt of travel support to attend CSTE meetings; and service on the board of the National Foundation of Infectious Disease (NFID) and receipt of travel support to attend NFID meetings. D. R. P. reports support for this work and support for attending meetings and/or travel from the Division of Intramural Research, NIAID, NIH. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.

Introduction: Nontuberculous mycobacteria (NTM) are a diverse group of mycobacterial species that are ubiquitous in the environment. They are opportunistic pathogens that can cause a range of diseases, especially in individuals with underlying structural lung disease or compromised immune systems., Areas Covered: This paper provides an in-depth analysis of NTM infections, including microbiology, environmental sources and transmission pathways, risk factors for disease, epidemiology, clinical manifestations and diagnostic approaches, guideline-based treatment recommendations, drugs under development, and management challenges., Expert Opinion: Future approaches to the management of NTM pulmonary disease will require therapies that are well tolerated, can be taken for a shorter time period and perhaps less frequently, have few drug-drug interactions, and are active against the various strains of pathogens. As the numbers of infections increase, such therapies will be welcomed by clinicians and patients.

Purpose: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data., Methods: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment., Results: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped., Conclusion: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers., (© 2023. The Author(s).)

In recent years, the incidence and prevalence of pulmonary nontuberculous mycobacterial (NTM) disease have increased worldwide. Although the reasons for this increase are unclear, dealing with this disease is essential. Pulmonary NTM disease is a chronic pulmonary infection caused by NTM bacteria, which are ubiquitous in various environments. In Japan, Mycobacterium avium-intracellulare complex (MAC) accounts for approximately 90% of the causative organisms of pulmonary NTM disease, which is also called pulmonary MAC disease or pulmonary MAI disease. It is important to elucidate the pathophysiology of this disease, which occurs frequently in postmenopausal women despite the absence of obvious immunodeficiency. The pathophysiology of this disease has not been fully elucidated; however, it can largely be divided into bacterial (environmental) and host-side problems. The host factors can be further divided into immune and airway problems. The authors suggest that the triangular relationship between bacteria, immunity, and the airway is important in the pathophysiology of this disease. The latest findings on the pathophysiology of pulmonary NTM disease are reviewed., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Slowly growing nontuberculous mycobacteria (NTM) comprise a diverse group of environmental organisms, many of which are important human pathogens. The most common and well-known member of this group is Mycobacterium avium, the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) globally. This review focuses on the less common, but notable, species of slowly growing NTM with respect to lung disease. To prepare this article, literature searches were performed using each species name as the key word. Society guidelines were consulted, and relevant articles also were identified through the reference lists of key articles. The specific organisms highlighted include Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Although these organisms are closely related, they have distinct epidemiologic features and behavior as pathogens. Therefore, the diagnosis and management of NTM-PD require a nuanced approach that takes into consideration the unique characteristics of each species. There is limited evidence to inform the optimal treatment of NTM-PD. Antimicrobial therapy is often challenging because of the presence of drug resistance and few antibiotic options. Regimen selection should generally be guided by drug susceptibility testing, although the correlation between clinical outcomes and in vitro susceptibility thresholds has not been defined for most species., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Nontuberculous mycobacterial (NTM) pleuritis is an uncommon manifestation of NTM infection. Case reports and small case series have shown a variable clinical course and high mortality rates., Objective: To describe patients' characteristics, clinical presentation and outcomes of NTM pleural infections., Methods: A systematic review of cases of NTM pleural infections published in PubMed-indexed journals from 1980 to 2021., Results: A total of 206 cases of NTM pleural infections were found and analyzed. Fifty-eight percent of cases were males. The mean age was 57.5 yrs (range 9-87 yrs). Forty-three percent of patients were immunosuppressed, and 43% had a chronic lung disease; thirty-two percent had neither risk factor. In addition to the pleural infection, 67% of cases had a concurrent pulmonary NTM infection, and in 18 cases there was another extrapulmonary site of NTM infection. In 29% of cases the pleural infection was the sole manifestation of NTM disease. The most common isolated mycobacterium was Mycobacterium avium complex (65%). Fifty-three percent and 26% of patients required pleural effusion drainage and a surgical intervention, respectively, to treat the infection, in addition to anti-NTM chemotherapy. Forty percent of patients developed pneumothorax, 16% suffered from empyema, and 16.5% had broncho-pleural fistula. The reported mortality rate was 24%., Conclusion: NTM pleural infections may arise in immunocompetent and immunosuppressed patients, with or without chronic lung disease or concurrent NTM pulmonary infection. These infections carry a poor prognosis and a high risk of complications requiring surgical interventions in addition to anti-NTM chemotherapy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease., Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated., Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%)., Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation., Competing Interests: Declaration of competing interest CW is on an advisory board for Pfizer on COVID-19 treatments and was recently lecturing on future pandemics for pulmonology specialists for Novartis. All other authors have no competing interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Regarding to known association between underweight and non-tuberculous mycobacterial pulmonary disease (NTM-PD), the underweight was simply categorized as body mass index (BMI) less than 18.5 kg/m 2 , mainly because of its low prevalence. We aimed to better define the impact of BMI severity on NTM-PD development. We analysed health data from 4,332,529 individuals examined in 2009 and followed up until December 2017 to determine the incidence of NTM-PD. Based on the BMI in kg/m 2 , the population was categorized into mild (17.00-18.49), moderate (16.00-16.99), and severe underweight (< 16.00) groups. Using Cox proportional-hazards analyses, hazard ratios for NTM-PD were calculated according to the severity of underweight in reference to normal BMI (18.50-22.99). Over a median follow-up of 5.6 ± 1.2 years, 6223 participants developed NTM-PD. Risk of NTM-PD increased significantly with the severity of underweight: multivariate adjusted hazard ratios (95% confidence intervals) for mild, moderate, and severe underweight were 2.34 (2.17-2.52), 3.50 (3.07-3.99), and 4.35 (3.63-5.21), respectively. In subgroup analysis, being younger (< 65 years old) or male exacerbated the effect of severe underweight on the risk of NTM-PD. This study proved that as underweight categories became more severe, the risk of NTM-PD increased proportionally., (© 2022. The Author(s).)

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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

In mid-2014, Public Health Ontario Laboratories identified coincident increasing Mycobacterium avium isolation and falling M. xenopi isolation in the Toronto, Ontario, Canada, area. We performed a retrospective cohort of all patients in a Toronto clinic who began treatment for either M. avium or M. xenopi pulmonary disease during 2009-2012 (early period) or 2015-2018 (late period), studying their relative proportions and sputum culture conversion. We conducted a subgroup analysis among patients who lived in the Toronto-York region. The proportion of patients with M. avium was higher in the late period (138/146 [94.5%] vs. 82/106 [77.4%]; p<0.001). Among M. avium patients, conversion was lower in the late period (26.1% vs. 39.0%; p = 0.05). The increase in the proportion of patients with M. avium pulmonary disease and the reduction in the frequency of sputum culture conversion is unexplained but could suggest an increase in environmental M. avium exposure.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Hu, Wang, Li and Tang.)

Background: The number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly increasing globally, especially in the older population. However, there is a dearth of evidence regarding the impact of aging on the treatment outcomes of NTM-PD., Methods: We analyzed consecutive patients who satisfied the diagnostic criteria for Mycobacterium avium complex (MAC)-PD and received antibiotic treatment between January 2009 and December 2020 at a tertiary referral hospital in Korea. The main outcomes were (1) long-term treatment success, defined by negative culture conversion for more than 12 months; and (2) adverse drug reactions (ADRs). Multivariable logistic regression model was used to evaluate the association between age and main outcomes., Results: A total of 614 patients (median age, 65 years, interquartile range [IQR] 57-73 years; men, 35.3%) were included. Median treatment duration (530 days, IQR 290-678 days; P for trend < 0.001) and long-term treatment success (P for trend = 0.026) decreased, whereas ADRs (P for trend < 0.001) increased significantly with age. Multivariable analyses demonstrated that age ≥ 80 years was an independent factor associated with ADRs (adjusted odds ratio [aOR] 3.29; 95% confidence interval [CI] 1.05-10.28) and worse treatment outcome (aOR 0.42; 95% CI 0.19-0.91)., Conclusions: Aging is associated with worse treatment outcome and frequent ADRs of patients with MAC-PD. Individualized treatment with reduced-intensity may be a reasonable alternative for older adults., (© 2022. The Author(s).)

Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916 T ), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.

Background: There have been reports of increases in the incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in several countries, but no studies have analyzed claims data using laboratory tests. This study aimed to estimate the nationwide epidemiology and medical treatments of NTM-PD according to laboratory tests run in Korea., Methods: Using claims data from the Health Insurance Review and Assessment Service, we analyzed patients with nontuberculous mycobacterium (ICD-10: A31) who were diagnosed from Jan 2007 to Jun 2019. The incidence and prevalence of NTM-PD and whether related laboratory tests were performed were analyzed. Diagnostic code-based NTM-PD patients were defined as patients who had NTM as a diagnosis on at least 2 occasions within 180 days. Clinically refined NTM-PD patients were defined as those excluding hospital-diagnosed patients with acid-fast bacilli (AFB) culture rates less than 5%. Laboratory tests included AFB smears, AFB culture, NTM identification, and drug susceptibility tests (DSTs)., Results: A total of 60,071 diagnostic code-based NTM-PD patients were evaluated. Clinically refined NTM-PD included 45,321 patients, excluding 14,750 (24.6%) patients diagnosed in hospitals with low AFB culture rates. The annual incidence per 100,000 population increased from 2.9 cases in 2008 to 12.3 cases in 2018. The annual prevalence per 100,000 population increased from 5.3 cases in 2008 to 41.7 cases in 2018. After removing outliers according to the AFB culture rate, a significant decrease in incidence was observed in women younger than 50 years. Among patients with clinically refined NTM-PD, the test rates for AFB culture, NTM identification, and DST were 84.3%, 59.1%, and 40.4%, respectively. From the outpatient clinic, 17,977 (39.7%) patients were prescribed drugs related to NTM treatment, with a median number of prescriptions of 7 (interquartile range (IQR) 3-11) and a median duration from the diagnosis to end of treatment of 330 (IQR 118-578) days., Conclusions: Although the incidence and prevalence of NTM-PD are on the rise, the recent surge in women 50 years of age is overestimated in patients not adequately tested. In claim-based studies, there may be limitations in estimating the epidemiological data with only the diagnostic codes., (© 2022. The Author(s).)

Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objective: To present the frequency and species diversity of non-tuberculous mycobacteria, estimate the prevalence of non-tuberculous mycobacterial pulmonary disease, describe the epidemiological profile, and determine the follow-up of patients with non-tuberculous mycobacterial pulmonary disease living in a region with a high burden of tuberculosis., Methods: This a retrospective cohort observational study using data records obtained from the Instituto Adolfo Lutz - Santos and from the São Paulo Sistema de Vigilância de Tuberculose do Estado de São Paulo in the period between 2000 and 2009. The studied variables were: socio-demographic characteristics, current and past history of tuberculosis, aspects related to diagnosis, and treatment and associated diseases., Results: We included 319 non-tuberculous mycobacteria isolates in the study, corresponding to 257 patients. The species Mycobacterium kansasii (28.5%) and Mycobacterium fortuitum (16.6%) presented the higher occurrence. In 10.9% (24) of the patients, there was a criterion for confirming a case of pulmonary disease due to non-tuberculous mycobacteria. In relation to gender and age, male and individuals over 50 years old were the most frequent. Considering the confirmed cases, 47.8% had a past history of tuberculosis., Conclusion: The lack of information about the cases is evident, since pulmonary disease due to non-tuberculous mycobacteria is not mandatory. The therapeutic regimen according to the identified species is fundamental for success in combating the infections caused by non-tuberculous mycobacteria. Besides that, information about the regional epidemiology of pulmonary disease caused by non-tuberculous mycobacteria and the search for associations with other comorbidities are important to establish the correct treatment. In order to improve surveillance of pulmonary diseases by non-tuberculous mycobacteria, we suggest the implantation of a sentinel surveillance and of population-based studies.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an uncommon mycobacterial infection characterized by worsening lung function and increased health care resource utilization; however, the overall risk for hospitalization among patients with NTM-PD remains unclear., Research Question: What is the hospitalization risk among older adults with NTM-PD?, Study Design and Methods: A retrospective, nested, case-control study was conducted by using the Medicare claims database. Cases were defined as patients with ≥ 2 NTM-PD claims ≥ 30 days apart between January 1, 2007, and December 31, 2015. The study included individuals aged ≥ 65 years with ≥ 12 months of continuous enrollment in both Parts A and B before the first NTM-PD diagnosis. Cases were matched 1:2 to Medicare beneficiaries without NTM-PD (control subjects) according to age and sex. Hospitalizations following the first NTM-PD claim were compared between case and control subjects by using univariate and multivariate analyses., Results: A total of 35,444 case subjects and 65,467 matched control subjects (mean age, 76.6 years; 70% female; ≥ 87% White) were identified. Baseline comorbidities, particularly pulmonary comorbidities, were more common in case subjects than in control subjects (81.1% vs 17.7% for COPD; 44.6% vs 0.6% for bronchiectasis). All-cause hospitalization was observed in 65.7% of case subjects and 44.9% of control subjects. Unadjusted annual hospitalization rates were significantly (P < .05) greater among case subjects than control subjects. Case subjects also had a significantly shorter time to hospitalization than control subjects. The increased burden due to hospitalization was reflected in multivariate analysis adjusting for baseline comorbidities. All-cause hospitalization in patients with NTM-PD relative to control subjects was 1.2 times more likely (relative risk, 1.23; 95% CI, 1.21-1.25; P < .0001) with a 46% greater hazard (hazard ratio, 1.46; 95% CI, 1.43-1.50; P < .0001)., Interpretation: Patients with NTM-PD were significantly more likely to be hospitalized, had greater annualized hospitalization rates, and had shorter time to hospitalization than age- and sex-matched control subjects without NTM-PD. These findings highlight the significantly increased burden of hospitalizations among patients with NTM-PD., (Published by Elsevier Inc.)

Background: The objective of the study was to describe the epidemiology, management and cost of non-tuberculous mycobacteria pulmonary disease (NTM-PD) in France., Methods: A retrospective analysis was performed using the SNDS ("Système national des données de santé") database over 2010-2017. Patients with NTM-PD were identified based on the ICD10 codes during hospitalizations and/or specific antibiotics treatment regimens. The study population was matched (age, sex and region) to a control group (1:3) without NTM-PD., Results: 5628 patients with NTM-PD (men: 52.9%, mean age = 60.9 years) were identified over the study period and 1433 (25.5%) were treated with antibiotics. The proportion of patients still receiving treatment at 6 and 12 months was 40% and 22%, respectively. The prevalence of NTM-PD was estimated at 5.92 per 100,000 inhabitants and the incidence rate of NTM-PD remained stable over time between 1.025/100,000 in 2010 and 1.096/100,000 in 2017. Patients with NTM-PD had more co-morbidities compared to controls: corticoids (57.3% vs. 33.8%), chronic lower respiratory disease (34.4% vs. 2.7%), other infectious pneumonia (24.4% vs. 1.4%), malnutrition (based on hospitalization with the ICD-10 code reported during a hospital stay as a main or secondary diagnosis) (22.0% vs. 2.0%), history of tuberculosis (14.1% vs. 0.1%), HIV (8.7% vs. 0.2%), lung cancer and lung graft (5.7% vs. 0.4%), cystic fibrosis (3.2% vs. 0.0%), gastro-esophageal reflux disease (2.9% vs. 0.9%) and bone marrow transplant (1.3% vs. 0.0%) (p < 0.0001). The mean Charlson comorbidity index score was 1.6 (vs. 0.2 for controls; p < 0.0001). NTM-PD was independently associated with an increased mortality rate with a hazard ratio of 2.8 (95% CI: 2.53; 3.11). Mortality was lower for patients treated with antibiotics compared to untreated patients (HR = 0.772 (95% CI [0.628; 0.949]). Annual total expenses the year following the infection in a societal perspective were € 24,083 (SD: 29,358) in NTM-PD subjects vs. € 3402 (SD: 8575) in controls (p < 0.0001). Main driver of the total expense for NTM-PD patients was hospital expense (> 50% of the total expense)., Conclusion: Patients with NTM-PD in France were shown to have many comorbidities, their mortality risk is high and mainly driven by NTM-PD, and their management costly. Only a minority of patients got treated with antibiotics and of those patients treated, many stopped their therapy prematurely. These results underline the high burden associated with NTM-PD and the need for improvement of NTM-PD management in France., (© 2021. The Author(s).)

Background: The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting., Methods: We conducted a retrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records., Results: Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was a significant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003)., Conclusion: The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD., (© 2021. Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.

Purpose: There is a dearth of data on epidemiology, diagnosis and management of slow growing non tuberculous mycobacteria(NTM) in India, despite being a TB endemic country. This study aims to describe the geographic distribution, risk factors, and the challenges in management of slow growing NTM causing pulmonary infections., Methods: Over a period of 3 years, all slow growing NTM received from pulmonary specimens at a tertiary care centre were further studied from electronic hospital records to correlate non tuberculous mycobacteria species with demographics, geographic location, describe comorbidities including immunosuppression, radiologic findings and treatment regimes., Results: M.intracellullare was found in the majority of isolates with significant geographic variation and M.simiae the second commonest found exclusively in southern states. Common comorbidities included a previous history of treatment for tuberculosis, structural lung disease as well as systemic risk factors. Disseminated disease only occurred in immunocompromised hosts as was expected, but at a high rate of 44%. Treatment completion and outcomes were difficult to attain in our population., Conclusion: The burden of NTM infection and its management in India remain a challenge. Ensuring it is made a notifiable disease may improve the current situation., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: Bronchoscopy is recommended for patients with suspected nontuberculous mycobacterial pulmonary disease (NTM-PD) whose sputum culture results are consistently negative or from whom adequate sputum samples cannot be obtained. Post-bronchoscopy sputum (PBS) collection is recommended for patients with suspected tuberculosis who undergo bronchoscopy. However, it remains unclear whether PBS collection can increase the diagnostic yield of NTM-PD., Methods: Patients with suspected NTM-PD who underwent diagnostic bronchoscopy from January 1, 2017 to June 30, 2020 at the Seoul National University Hospital were included in the study. They were divided into the sputum culture-negative and scanty sputum groups. The results of mycobacterial cultures from bronchial washing specimens and PBS were compared between these groups., Results: In total, 141 patients were included in the study; there were 39 and 102 patients in the sputum culture-negative and scanty sputum groups, respectively. Nontuberculous mycobacteria were cultured from bronchial washing specimens collected from 38.3% (54/141) of all patients (30.7% [12/39] patients in the sputum culture-negative group and 41.2% [42/102] patients in the scanty sputum group; P = 0.345). Nontuberculous mycobacteria were exclusively cultured from PBS collected from 3.5% (5/141) of all patients (7.7% [3/39] patients in the sputum culture-negative group and 2.0% [2/102] patients in the scanty sputum group; P = 0.255)., Conclusions: Additional PBS collection improved diagnostic yield marginally in patients with suspected NTM-PD who undergo bronchoscopy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and 193 species of NTM have been discovered thus far. NTM species vary in virulence from benign environmental organisms to difficult-to-treat human pathogens. Pulmonary infections remain the most common manifestation of NTM disease in humans and bronchiectasis continues to be a major risk factor for NTM pulmonary disease (NTM PD). This article will provide a useful introduction and framework for clinicians involved in the management of bronchiectasis and NTM. It includes an overview of the epidemiology, pathogenesis, diagnosis, and management of NTM PD. We will address the challenges faced in the diagnosis of NTM PD and the importance of subspeciation in guiding treatment and follow-up, especially in Mycobacterium abscessus infections. The treatment of both Mycobacterium avium complex and M. abscessus , the two most common NTM species known to cause disease, will be discussed in detail. Elements of the recent ATS/ERS/ESCMID/IDSA NTM guidelines published in 2020 will also be reviewed., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Lymphopenia has been reported as a risk factor for poor prognosis in various infectious diseases, including Mycobacterium avium complex lung disease (MAC-LD), and recurrence in several infectious diseases. However, the association between lymphopenia and the risk of redeveloping nontuberculous lung disease (NTM-LD) after completed treatment for MAC-LD is unknown., Methods: We performed a retrospective cohort study with 147 patients with MAC-LD who successfully completed guideline-based therapy. Lymphopenia was defined as an absolute lymphocyte count (ALC) <1000 cells/μL based on commonly accepted reference values., Results: During the median follow-up period of 41.9 months after treatment completion, 59 (40.1%) patients redeveloped NTM-LD. Patients with NTM-LD redevelopment had significantly lower posttreatment ALCs (median, 1260 vs 1420 cells/μL) than those without, and the univariate Cox proportional hazard analysis identified posttreatment ALC as a predictive factor for redevelopment (hazard ratio, .94 [95% confidence interval, .89-.99] for every increase of 100 cells/μL; P = .04). In the multivariate analysis, posttreatment ALC and the extent of bronchiectasis were independently associated with NTM-LD redevelopment. The cumulative rate of NTM-LD redevelopment was significantly higher in patients with posttreatment lymphopenia than in those without (P = .008)., Conclusions: Posttreatment lymphopenia could predict an increased risk of NTM-LD redevelopment after completed treatment for MAC-LD., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Nontuberculous mycobacteria (NTM) are diverse microbial species encompassing commensals and pathogens with the ability to cause pulmonary disease in both immunocompetent and immunocompromised individuals. In contrast to Mycobacterium tuberculosis , which has seen a reduction in disease rates in developed countries, the incidence and prevalence of NTM disease is increasing. NTM are difficult to treat with standard antimicrobial regimens and may contain both virulence and antibiotic-resistance genes with potential for pathogenicity. With the advent of molecular techniques, it has been elucidated that these organisms do not reside in isolation and are rather part of a complex milieu of microorganisms within the host lung microbiome. Over the last decade, studies have highlighted the impact of the microbiome on host immunity, metabolism and cell-cell communication. This recognition of a broader community raises the possibility that the microbiome may disrupt the balance between infection and disease. Additionally, NTM disease progression and antimicrobial therapy may affect the healthy steady state of the host and function of the microbiome, contributing to further dysbiosis and clinical deterioration. There have been limited studies assessing how NTM may influence the relationship between microbiome and host. In this review, we highlight available studies about NTM and the microbiome, postulate on virulence mechanisms by which these microorganisms communicate and discuss implications for treatment., Competing Interests: Conflict of interest: C.S. Thornton has nothing to disclose. Conflict of interest: M. Mellett has nothing to disclose. Conflict of interest: J. Jarand has nothing to disclose. Conflict of interest: L. Barss has nothing to disclose. Conflict of interest: S.K. Field reports grants and personal fees from GSK, Novartis and Boehringer-Ingelheim; grants from InsMed; and personal fees from Teva, Canadian Agency for Drugs and Health Technologies (CADTH), and Grifols, outside the submitted work. Conflict of interest: D.A. Fisher has nothing to disclose., (Copyright ©The authors 2021.)

Background: Nontuberculous mycobacteria (NTM) are opportunistically pathogenic bacteria that are found abundantly in the soil and water. Susceptible individuals exposed to NTM-containing aerosols from environmental sources may develop NTM pulmonary disease (NTM-PD). Reported survival after NTM-PD diagnosis varies widely among existing studies. Prior work has suggested that mortality among persons with NTM-PD is primarily driven by comorbidities rather than NTM-PD., Methods: We retrospectively identified a cohort of patients in the Duke University Health System who were diagnosed with NTM-PD between 1996 and 2015. Hospitalizations and survival were compared among patients with NTM-PD with and without other comorbidities. Additionally, survival among patients with NTM-PD was compared with standardized mortality data for a similar cohort of the general population., Results: Patients with NTM-PD without other comorbidities had 0.65 hospitalizations/1000 patient-days compared with 1.37 hospitalizations/1000 patient-days for patients with other comorbidities. Compared with a cohort of the general population, expected survival decreased by approximately 4 years for a diagnosis of NTM-PD without comorbidities and 8.6 years for a diagnosis of NTM-PD with comorbidities. Mortality 5 years after diagnosis was 25.0% and 44.9% among NTM patients without and with comorbidities, respectively, compared with 5.7% in the general-population cohort., Conclusions: NTM-PD was associated with significant morbidity that was worse in patients with comorbidities. Patients with NTM-PD, even without comorbidities, had worse survival than expected., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.

Introduction: Management of nontuberculous mycobacterial lung disease (NTM-LD) can be encumbered by difficult diagnostic criteria and complex treatment decisions. As prevalence of this debilitating, often refractory, progressive lung disease increases globally, management must evolve beyond antimicrobials to encompass holistic and customized treatments coordinated by practitioners across various specialties., Areas Covered: This review aims to complement the recently updated NTM-LD treatment guidelines and expand current approaches to diagnosis, treatment, and disease management in a multidisciplinary dimension. The foundation of effective long-term management of NTM-LD is awareness of diagnostic criteria, individual patient risk factors, and the importance of managing underlying pulmonary and nonpulmonary comorbidities. The value of adopting all available pharmacological and nonpharmacological treatment modalities with a patient-centered approach to address the needs of long-term patient care cannot be minimized., Expert Opinion: This section, while acknowledging the limited advances in understanding of NTM-LD and the availability of newer diagnostic and therapeutic tools over the last decade, underscores the need for a programmatic approach to this chronic, debilitating pulmonary infection. This will not only lead to more comprehensive patient care with better outcomes, but will also inspire and activate robust networks of research and public health initiatives in this field.

Background: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States., Methods: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria., Results: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%., Conclusions: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Administrative claims data are prone to underestimate the burden of non-tuberculous mycobacterial pulmonary disease (NTM-PD)., Methods: We developed machine learning-based algorithms using historical claims data from cases with NTM-PD to predict patients with a high probability of having previously undiagnosed NTM-PD and to assess actual prevalence and incidence. Adults with incident NTM-PD were classified from a representative 5% sample of the German population covered by statutory health insurance during 2011-2016 by the International Classification of Diseases, 10th revision code A31.0. Pre-diagnosis characteristics (patient demographics, comorbidities, diagnostic and therapeutic procedures, and medications) were extracted and compared to that of a control group without NTM-PD to identify risk factors., Results: Applying a random forest model (area under the curve 0.847; total error 19.4%) and a risk threshold of >99%, prevalence and incidence rates in 2016 increased 5-fold and 9-fold to 19 and 15 cases/100,000 population, respectively, for both coded and non-coded vs. coded cases alone., Conclusions: The use of a machine learning-based algorithm applied to German statutory health insurance claims data predicted a considerable number of previously unreported NTM-PD cases with high probabilty., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) have been increasing worldwide. The risk of NTM-PD may be higher in undernourished populations. In this study, we tried to elucidate the impact of body mass index (BMI) and its change on development of NTM-PD.We performed a retrospective cohort study including South Koreans aged >40 years who underwent biennial National Health Insurance System (NHIS) health check-ups in both 2005 and 2009 or 2006 and 2010. We monitored eligible individuals from the study initiation date (NHIS health check-up date in 2009 or 2010) until the diagnosis of NTM-PD or until December 31, 2017. Enroled individuals were classified based on BMI at initiation date. By calculating hazard ratios, we compared NTM-PD incidence per 100   000 person-years by BMI group and by BMI change.A total of 5   670   229 individuals were included in the final analysis. Compared with the BMI <18.5 kg·m -2 group, the incidence of NTM-PD gradually decreased with increased BMI (adjusted hazard ratio 0.38, 95% confidence interval (CI) 0.35-0.42 for BMI 18.5-22.9; 0.17, 95% CI 0.15-0.19 for BMI 23-24.9; 0.1, 95% CI 0.09-0.11 for BMI 25-29.9; and 0.1, 95% CI 0.07-0.13 for BMI ≥30). A BMI decrease of ≥1 kg·m -2 over 4 years increased the incidence of NTM-PD (adjusted hazard ratio 1.08, 95% CI 1.01-1.16) whereas a BMI increase of ≥1 kg·m -2 decreased the incidence of NTM-PD (adjusted hazard ratio 0.77, 95% CI 0.71-0.83).In conclusion, BMI was inversely related to development of NTM-PD and weight loss increased the risk of NTM-PD., Competing Interests: Conflict of interest: J.H. Song has nothing to disclose. Conflict of interest: B.S. Kim has nothing to disclose. Conflict of interest: N. Kwak has nothing to disclose. Conflict of interest: K-D. Han has nothing to disclose. Conflict of interest: J-J. Yim has nothing to disclose., (©ERS 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Background/aims: The incidence rate of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. However, data regarding the age- and sex-specific epidemiology of NTM-PD are limited. This study aimed to investigate the long-term epidemiologic trends of NTM-PD within the recent 11- year period in a tertiary referral hospital in Korea., Methods: We retrospectively reviewed the medical records of the patients diagnosed with NTM-PD between January 2006 and December 2016 at Severance Hospital, South Korea., Results: There were 1,017 incident cases with NTM-PD during the study period. The mean age was 62.7 years, and 41.2% were men. Women were younger than men (59.9 years vs. 66.7 years, p < 0.001) and a higher proportion of women had bronchiectasis (88.6% vs. 77.1%, p < 0.001). The incidence rates of NTM-PD annually increased by 14% (95% confidence interval, 10% to 19%) from 1.2 in 2006 to 4.8 in 2016 (per 100,000 patients-year). The peak incidence rate was in the 50s for women and in the 70s for men, except for those aged ≥ 80 years. Mycobacterium avium complex was the most common causative species of NTM-PD (63.6%)., Conclusion: The incidence rate of NTM-PD in a tertiary referral hospital in South Korea continued to increase from 2006 to 2016. Furthermore, there were age- and sex-related differences in the clinical characteristics, which might contribute to understanding the nature of the disease and inherited and acquired host factors.

Background: Nontuberculous mycobacterial (NTM) lung disease is one of a growing number of chronic health problems that is difficult to cure in aging societies. While it is important to be vigilant about associated comorbidities in order to provide better patient care, data on the prevalence of comorbidities stratified by country or region are scarce. We aimed to elucidate the comorbidities associated with NTM disease based on Japanese health insurance claims data., Methods: Cross-sectional analyses were performed using the claims data for 2014 provided by the Japan Medical Data Center Co., Ltd. Patients aged 20-75 years with ≥3 claims associated with NTM disease were identified and matched to 10 sex-and-age-matched controls that had never made a claim for NTM disease. Thirty-one comorbidities previously suspected to be associated with NTM disease were selected, and the prevalence of these comorbidities compared between cases and controls., Result: Overall, 419 NTM patients (134 males and 285 females) and 4190 non-NTM controls were identified from the JMDC database. Aspergillosis, asthma, chronic heart failure, diffuse panbronchiolitis, gastroesophageal reflux, interstitial pneumonia, lung cancer, cancer other than breast, lung, ovary, or prostate cancer, and rheumatoid arthritis were associated with NTM disease in both males and females. Chronic obstructive pulmonary disease was associated with NTM in males while chronic kidney disease, osteoporosis, and Sjögren syndrome were associated with NTM in females., Conclusion: NTM disease was associated with multiple comorbidities that should be considered when providing medical care to individuals with NTM disease.

Objectives: As the number of patients with nontuberculous mycobacterial pulmonary disease (NTMPD) increases, surgical treatment to control disease becomes more important. However, postoperative outcomes and predictors of recurrence have been insufficiently evaluated., Methods: We retrospectively investigated 100 patients with NTMPD who underwent pulmonary resection from 2009 to 2016 at our institution. Clinical data of patients with and without postoperative recurrence were statistically compared. Recurrence was defined as microbiological re-identification or computed tomography findings highly suspicious for relapse after excluding other diseases. Recurrence-free survival was calculated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Predictive factors were evaluated using univariate and multivariate analyses., Results: Nine patients experienced recurrence. A significant difference in recurrence-free survival was detected between patients with and without a positive preoperative sputum culture (P = 0.000942). Moreover, patients with a positive preoperative sputum smear (≥ 2 +) had a significantly higher recurrence rate than those who did not (P = 0.000216). Multivariate analysis revealed that preoperative sputum smear (≥ 2 +) is an independent risk factor for recurrence after pulmonary resection for NTMPD (odds ratio, 7.38; 95% confidential interval, 1.29-42.2; P = 0.024)., Conclusions: NTM discharge might have an impact on postoperative recurrence of NTMPD patients without residual cavitary lesions. Preoperative NTM discharge should be minimized by optimizing medical therapy before surgical treatment to improve the postoperative course. Intensive follow-up and prolonged postoperative medical therapy should be considered for patients without a sufficient reduction in bacterial discharge before pulmonary resection.

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001-2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.

As a cause of lung disease (LD), Mycobacterium kansasii is regarded as a highly virulent species among nontuberculous mycobacteria (NTM). Both the frequency of M. kansasii isolates and global prevalence of M. kansasii-LD have increased gradually over recent decades. Treatment of M. kansasii-LD is recommended because of the disease's poor prognosis and fatal outcome. The decision on the optimal time point for treatment initiation should be based on both the benefits and risks posed by multiple antimicrobial agents. For treatment-naïve patients with M. kansasii-LD, rifampin-containing multiple antimicrobial regimens for ≥12 months after culture negative conversion are effective. However, some challenges remain, such as determining the precise length of treatment duration as well as addressing intolerable adverse effects, the uncertain effectiveness of isoniazid and ethambutol in treatment, the uncertain correlation between in vitro drug susceptibility testing and clinical outcomes, and the increasing prevalence of clarithromycin-resistant M. kansasii isolates. Short-course and effective therapies must be developed. New candidate drugs, such as tedizoid and clofazimine, exhibit excellent antimycobacterial activity against M. kansasii in vitro, but in vivo studies of their clinical applications are lacking. This paper reviews the treatment, outcomes and future directions in patients with M. kansasii-LD., 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.)