Section 4: What is the evidence for transmission of NTM between individuals? 

Recommendation 

Section 5: How should the lung disease attributable to NTM infection be defined? 

Recommendation 

Good practice point 

Section 6: What samples should be used to detect pulmonary non-tuberculous mycobacterial infection? 

Recommendations 

Good practice points 

Section …

/pdf/british-thoracic-society-guidelines-for-the-management-of-35wnkt4897.pdf

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

The future of cystic fibrosis care: a global perspective

Infections caused by non-tuberculous mycobacteria (NTM) are increasing globally and are notoriously difficult to treat due to intrinsic resistance of these bacteria to many common antibiotics. NTM are diverse and ubiquitous in the environment, with only a few species causing serious and often opportunistic infections in humans, including Mycobacterium abscessus. This rapidly growing mycobacterium is one of the most commonly identified NTM species responsible for severe respiratory, skin and mucosal infections in humans. It is often regarded as one of the most antibiotic-resistant mycobacteria, leaving us with few therapeutic options. In this Review, we cover the proposed infection process of M. abscessus, its virulence factors and host interactions and highlight the commonalities and differences of M. abscessus with other NTM species. Finally, we discuss drug resistance mechanisms and future therapeutic options. Taken together, this knowledge is essential to further our understanding of this overlooked and neglected global threat. Non-tuberculous mycobacteria, such as Mycobacterium abscessus, are an increasing global health burden, in part due their extensive drug resistance. In this Review, Johansen, Herrmann and Kremer discuss the infection process, host interactions, mechanisms of drug resistance and drug development.

Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus.

The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of Mycobacterium tuberculosis (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.

/pdf/the-rise-of-non-tuberculosis-mycobacterial-lung-disease-5cut5bnjlo.pdf

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

NTM drug discovery: status, gaps and the way forward

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium

COVID-19-associated pulmonary aspergillosis (CAPA) refers to co-infection with Aspergillus spp. in patients with COVID-19. It has a higher mortality rate when compared with patients only infected with COVID-19, but we still know little about the epidemiology, diagnosis, and best treatment options for patients with CAPA. We report our findings from a year-long retrospective case series of patients with CAPA in two tertiary hospitals in the United Kingdom. We included all patients admitted to critical care with CAPA between March 2020–2021. We used the European Confederation for Medical Mycology and the International Society for Human and Animal Mycology consensus criteria to categorise CAPA. Demographic data, patients’ co-morbidities, time to and method of diagnosis, COVID-19 and aspergillosis treatment, and outcomes were analysed. Thirteen patients were diagnosed with probable CAPA between October/2020–March/2021, and 54.8% also had hypertension. Diagnosis was established after a median of 18 days post-COVID-19 infection, and a median of 7 days post-intubation. All patients had received corticosteroids, as well as tocilizumab (7; 53.8%) and remdesivir (3; 23%). Eleven patients received antifungal treatment. Nine (69%) patients died by 30 days post-ICU admission, one patient died on day 32, and three (23%) patients survived. CAPA has a very high mortality rate. We also identified three areas that merit further investigation: lack of positive tests between March–October 2020; COVID-19 treatments and possible relationship with increased CAPA rates; and the rationale behind antifungal treatment in our hospitals compared to recommended treatment in the literature.

/pdf/covid-19-associated-pulmonary-aspergillosis-a-year-long-ijbffclq.pdf

COVID-19-Associated Pulmonary Aspergillosis: A Year-Long Retrospective Case Series

Use of long-term ventilation (LTV) benefits patients with a diverse range of conditions, including Duchenne muscular dystrophy, motor neurone disease and scoliosis [1]. Patients with pulmonary disease as well as neuromuscular disease can benefit from LTV. COPD patients treated with LTV experience a reduction in hospital admissions and the use of LTV in cystic fibrosis (CF) patients is increasing [2, 3]. Guidelines suggest that exhaled gases do not reach the outlet of noninvasive ventilators in clinical use. In this study, when tidal volumes exceeded 800 mL, exhaled gases did reach the ventilator, leading to a risk of cross-infection between users. https://bit.ly/3EdvtY6

Exhaled gases and the potential for cross-infection via noninvasive ventilation machines

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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium

COVID-19-Associated Pulmonary Aspergillosis: A Year-Long Retrospective Case Series

Exhaled gases and the potential for cross-infection via noninvasive ventilation machines