-
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 -
Cell May 2022Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung...
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.
Topics: Anti-Bacterial Agents; Bacteriophages; Cystic Fibrosis; Humans; Lung; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 35568033
DOI: 10.1016/j.cell.2022.04.024 -
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 -
European Respiratory Review : An... Mar 2022Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently... (Review)
Review
Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently associated with adverse effects and has variable success. In this review, we consider the factors influencing clinicians when treating NTM-PD and discuss outcomes from key studies on the pharmacological management of complex pulmonary disease and pulmonary disease. We highlight issues relating to treatment-related toxicity and provide an overview of repurposed and emerging therapies for NTM-PD.
Topics: Humans; Lung; Lung Diseases; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection
PubMed: 35140106
DOI: 10.1183/16000617.0212-2021 -
Science (New York, N.Y.) Apr 2021Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the...
Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.
Topics: Communicable Diseases, Emerging; Datasets as Topic; Epigenesis, Genetic; Evolution, Molecular; Gene Transfer, Horizontal; Genetic Fitness; Genome, Bacterial; Humans; Lung; Mutation; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Pneumonia, Bacterial; Virulence
PubMed: 33926925
DOI: 10.1126/science.abb8699 -
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 -
Nature Medicine May 2019A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung...
A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
Topics: Adolescent; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Genetic Engineering; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Phage Therapy
PubMed: 31068712
DOI: 10.1038/s41591-019-0437-z -
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 -
Molecular Microbiology Mar 2022Respiratory infections remain a major global health concern. Tuberculosis is one of the top 10 causes of death worldwide, while infections with Non-Tuberculous...
Respiratory infections remain a major global health concern. Tuberculosis is one of the top 10 causes of death worldwide, while infections with Non-Tuberculous Mycobacteria are rising globally. Recent advances in human tissue modeling offer a unique opportunity to grow different human "organs" in vitro, including the human airway, that faithfully recapitulates lung architecture and function. Here, we have explored the potential of human airway organoids (AOs) as a novel system in which to assess the very early steps of mycobacterial infection. We reveal that Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mabs) mainly reside as extracellular bacteria and infect epithelial cells with very low efficiency. While the AO microenvironment was able to control, but not eliminate Mtb, Mabs thrives. We demonstrate that AOs responded to infection by modulating cytokine, antimicrobial peptide, and mucin gene expression. Given the importance of myeloid cells in mycobacterial infection, we co-cultured infected AOs with human monocyte-derived macrophages and found that these cells interact with the organoid epithelium. We conclude that adult stem cell (ASC)-derived AOs can be used to decipher very early events of mycobacteria infection in human settings thus offering new avenues for fundamental and therapeutic research.
Topics: Humans; Macrophages; Mycobacterium abscessus; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Organoids; Tuberculosis
PubMed: 34605588
DOI: 10.1111/mmi.14824