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The European Respiratory Journal Jul 2020Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and...
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as complex, , and among the slowly growing NTM and among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Topics: Adult; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria
PubMed: 32636299
DOI: 10.1183/13993003.00535-2020 -
Clinical Infectious Diseases : An... Aug 2020Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and...
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Topics: Adult; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria
PubMed: 32628747
DOI: 10.1093/cid/ciaa241 -
The Indian Journal of Medical Research Sep 2020Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent... (Review)
Review
Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.
Topics: Diagnostic Tests, Routine; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 33107481
DOI: 10.4103/ijmr.IJMR_902_20 -
Journal of Biomedical Science Jun 2020Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis... (Review)
Review
Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.
Topics: Female; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Tuberculosis
PubMed: 32552732
DOI: 10.1186/s12929-020-00667-6 -
International Journal of Infectious... Dec 2022To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. (Review)
Review
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.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium abscessus; Lung Diseases; Pneumonia
PubMed: 36244600
DOI: 10.1016/j.ijid.2022.10.013 -
Clinical Infectious Diseases : An... Aug 2020Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and...
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Topics: Adult; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria
PubMed: 32797222
DOI: 10.1093/cid/ciaa1125 -
Frontiers in Immunology 2020The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of (TB) were... (Review)
Review
The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of (TB) were once thought to be harmless environmental saprophytics and only dangerous to individuals with defective lung structure or the immunosuppressed. However, NTM are now commonly infecting seemingly immune competent children and adults at increasing rates through pulmonary infection. This is of concern as the pathology of NTM is difficult to treat. Indeed, NTM have become extremely antibiotic resistant, and now have been found to be internationally dispersed through person-to-person contact. The reasons behind this NTM increase are only beginning to be elucidated. Solutions to the problem are needed given NTM disease is more common in the tropics. Importantly, 40% of the world's population live in the tropics and due to climate change, the Tropics are expanding which will increase NTM infection regions. This review catalogs the global and economic disease burden, at risk populations, treatment options, host-bacterial interaction, immune dynamics, recent developments and research priorities for NTM disease.
Topics: Age Distribution; Climate Change; Cost of Illness; Global Health; Host-Pathogen Interactions; Humans; Mycobacterium Infections, Nontuberculous; Opportunistic Infections; Pneumonia, Bacterial; Research; Risk; Sex Distribution; Tropical Climate; Water Microbiology
PubMed: 32194556
DOI: 10.3389/fimmu.2020.00303 -
The European Respiratory Journal Jul 2019Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a challenging infection which is becoming increasingly prevalent, particularly in the elderly, for reasons... (Review)
Review
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a challenging infection which is becoming increasingly prevalent, particularly in the elderly, for reasons which are unknown. While underlying lung disease is a well-established risk factor for NTM-PD, it may also occur in apparently healthy individuals. No single common genetic or immunological defect has been identified in this group, and it is likely that multiple pathways contribute towards host susceptibility to NTM-PD which further interact with environmental and microbiological factors leading to the development of disease.The diagnosis of NTM-PD relies on the integration of clinical, radiological and microbiological results. The clinical course of NTM-PD is heterogeneous, with some patients remaining stable without the need for treatment and others developing refractory disease associated with considerable mortality and morbidity. Treatment regimens are based on the identity of the isolated species, drug sensitivity testing (for some agents) and the severity of disease. Multiple antibiotics are typically required for prolonged periods of time and treatment is frequently poorly tolerated. Surgery may be beneficial in selected cases. In some circumstances cure may not be attainable and there is a pressing need for better regimens to treat refractory and drug-resistant NTM-PD.This review summarises current knowledge on the epidemiology, aetiology and diagnosis of NTM-PD and discusses the treatment of two of the most clinically significant species, the and complexes, with a focus on refractory disease and novel therapies.
Topics: Antitubercular Agents; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Pneumonectomy; Recurrence
PubMed: 31221809
DOI: 10.1183/13993003.00250-2019 -
Frontiers in Cellular and Infection... 2021(MABC is one of the most clinically relevant species among nontuberculous mycobacteria. MABC's prevalence has increased over the last two decades. Although these... (Review)
Review
(MABC is one of the most clinically relevant species among nontuberculous mycobacteria. MABC's prevalence has increased over the last two decades. Although these changes can be explained by improvements in microbiological and molecular techniques for identifying species and subspecies, a higher prevalence of chronic lung diseases may contribute to higher rates of MABC. High rates of antimicrobial resistance are seen in MABC, and patients experience multiple relapses with low cure rates. This review aims to integrate existing knowledge about MABC epidemiology, microbiological identification and familiarize readers with molecular mechanisms of resistance and therapeutic options for pulmonary infections with MABC.
Topics: Anti-Bacterial Agents; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Nontuberculous Mycobacteria
PubMed: 33981630
DOI: 10.3389/fcimb.2021.659997 -
Cell Nov 2023Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with...
Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.
Topics: Humans; Male; Cell Cycle Proteins; Interferon-gamma; Interleukin-12; Interleukin-23; Janus Kinase 2; Mycobacterium; Mycobacterium Infections; Oncogene Proteins
PubMed: 37875108
DOI: 10.1016/j.cell.2023.09.024