Authors: Ian Mason Freelance Medical Writer
The International Congress of the European Respiratory Society (ERS), 15–19 September, Paris (France), is the largest respiratory medicine meeting in the world. Non-tuberculous mycobacteria lung disease (NTM-LD) was included in the huge range of respiratory diseases discussed at the 2018 congress.
The record number of sessions on NTM-LD at this year’s ERS Congress shows the increasing interest from clinicians and researchers in these infections, and their rising incidence and prevalence.
NTM are a group of opportunistic bacterial pathogens, and patients with chronic respiratory diseases such as bronchiectasis, chronic obstructive pulmonary disease (COPD) or cystic fibrosis are more susceptible to NTM infection.
Testing bronchiectasis patients for NTM-LD
According to Professor Michael Loebinger, Consultant Respiratory Physician at London’s Royal Brompton Hospital, UK, all bronchiectasis patients should be tested for NTM infection, as it may be under-recognized .
Looking at data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Bronchiectasis Registry cohort, Professor Loebinger investigated the frequency of NTM-testing in bronchiectasis patients.
Only 35% of patients in the Bronchiectasis Registry were tested for NTM during the first year. NTM-testing was higher in countries with a high prevalence of tuberculosis (TB). Overall, NTM-testing was more common in patients with a history of NTM or more severe bronchiectasis.
Looking at bronchiectasis patients with active or previous NTM infection, he reported that the majority had Mycobacterium avium complex (MAC) infection. Those with active NTM were generally older and female, with lower mean BMI. However, the likelihood of being tested for NTM was not linked to the presence of these risk factors.
Practical update on the management of NTM-LD
NTM-LD also featured in a ‘state of the art’ session on the management of respiratory infections. Dr Jakko van Ingen, Consultant Clinical Microbiologist, Radboud UMC, Nijmegen, the Netherlands, discussed the need for a multidisciplinary approach to NTM-LD . Dr van Ingen highlighted that although multidisciplinary teams are generally led by pulmonologists, they are supported by microbiologists, pharmacists, radiologists and infectious disease physicians.
According to Dr van Ingen, with the use of guideline-based therapy (rifampicin/ ethambutol/ macrolide-based regimen) prolonged culture conversion can be achieved in around 70% of patients with MAC NTM-LD. However, according to a survey in five European countries and Japan, only 9% of patients with MAC NTM-LD received 6 months of guideline recommended therapy. Dr van Ingen noted that much of the non-adherence to guidelines can be explained by intolerance to treatment, particularly rifampicin. He mentioned that new treatments were coming, with recent results showing that the addition of amikacin liposome inhalation solution to guideline-based therapy for treatment-refractory MAC lung disease achieved significantly greater culture conversion by month 6 than guideline-based therapy alone, with comparable rates of serious adverse events. Multiple trials of clofazimine-containing regimens are also ongoing for this indication.
The challenges of managing NTM-LD
A talk by Professor James Chalmers, University of Dundee School of Medicine, UK, further highlighted the substantial challenges in managing NTM-LD .
One key challenge is the lack of dependable specialist advice or information on NTM-LD for clinicians. Other challenges highlighted by Professor Chalmers included treating elderly patients with NTM-LD and comorbidities, delays in diagnosis due to lack of NTM testing and managing drug toxicity.
However, Professor Chalmers said that despite these challenges the management of NTM has reached a ‘turning point’. Citing the new drugs, clinical trials and public grants for NTM that now exist, as well as European and American registries and clinical guidelines, he predicted that the next 5 years would be the ‘age of evidence-based medicine for NTM’.
NTM research updates
Treatment outcome risk factors in MAC lung disease
In macrolide-susceptible MAC lung disease, mean inhibitory concentrations (MICs) of 8 μg/ml or more for rifampin and ethambutol and positive initial sputum acid-fast bacilli (AFB) smear were identified as independent risk factors associated with unfavorable response to treatment . The study, presented by Dr Byoung Soo Kwon, Asan Medical Centre, Seoul, South Korea, found that treatment success rate tended to decrease with increasing MICs for both antibiotics. He said the study will help clarify the relationship between the in vitro susceptibilities of rifampin and ethambutol and clinical response in MAC lung disease.
The clinical significance of Mycobacterium triplex isolates
Dr Justine Gibson, Princess Alexandra Hospital, Brisbane, Australia, presented a review of 43 cases showing that the spectrum of disease and risk factors associated with Mycobacterium triplex pulmonary infections are similar to those for other slow-growing NTM species. She highlighted that treatment of M. triplex NTM-LD proved challenging, and although optimal antimicrobial regimens remain to be determined macrolides should form part of the regimen as macrolide-resistance remains uncommon for this species .
Non-adherence to guidelines could contribute to macrolide resistance
According to Dr Kiyohiko Izumi, TB Research Institute, Tokyo, Japan, if macrolide resistance is to be avoided clinicians need better education on NTM treatment guidelines. Studying a Japanese national database of medical claims, he found that around one in three patients were prescribed ‘non-standard’ (NS) regimens associated with macrolide resistance. Age and comorbidities such as rheumatoid arthritis and COPD were risk factors for receiving NS therapy . In another presentation, Dr Kozo Morimoto also reported sporadic macrolide monotherapy before and after standard treatment .
Six-minute walk test as a quality of life (QoL) measure
According to a cross-sectional study presented by Dr Kazuma Yagi, Keio University Hospital, Tokyo, Japan, 6-minute walk duration and final Borg scale, parameters of the 6-minute walk test, are useful for evaluating health-related QoL in patients with pulmonary MAC disease .
Injectable aminoglycoside in cavitary MAC lung disease
Injectable aminoglycoside with oral antibiotics is recommended for cavitary MAC lung disease; however, the optimal treatment duration remains unclear. A study presented by Dr Ock-Hwa Kim, Asan Medical Centre, Seoul, looked at 101 patients to clarify optimal treatment duration. They found that patients who received aminoglycoside for ≥90 days had significantly higher success rates than those treated for less than 90 days .
Effects of alcohol consumption on NTM-LD treatment outcome
Dr Maria Jacob, Porto, Portugal, highlighted the need to monitor NTM-LD patients’ alcohol consumption. Her retrospective analysis of 610 NTM-LD patients found that alcohol consumption was estimated to double the odds for an unsuccessful treatment outcome .
Genomic mapping reveals the pathophysiology of Mycobacterium abscessus
New genomic mapping data for Mycobacterium abscessus, the most lethal and frequent multidrug-resistant mycobacterial infection in the developed world was presented by Dr Lucas Boeck, Cambridge University, UK. It identified key functional networks controlling pathophysiology, including known and new determinants of resistance to amikacin, clarithromycin, clofazimine, cefoxitin and linezolid .
Financial and competing interests disclosure
This meeting report was funded by Insmed. The authors have no other relevant affiliations of financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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- Ringshausen F, Haworth C, Goeminne P et al. Characteristics of patients with pulmonary non-tuberculous Mycobacterial infection in bronchiectasis: Data from the EMBARC registry. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA348).
- van Ingen J. Non-tuberculous mycobacteria: how to treat these difficult infections. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract 2100).
- Chalmers J. NTM management- right time, right now. Insmed Scientific Dinner, Paris, France, 16th September 2018.
- Chong YP, Kim MN, Sung H et al. In vitro susceptibility to rifampin and ethambutol and treatment outcome in MAC lung disease. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA343).
- Baird T, Pandy S, Tolson C et al. The clinical significance of Mycobacterium triplex isolates in Queensland, Australia. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (ePoster Abstract PA344).
- Morimoto K, Uchimura K, Ato M et al. Population based survey on the NTM pulmonary disease treatment in Japan. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA346).
- Izumi K, Ato M, Mitarai S et al. Actual treatment practices of pulmonary nontuberculous mycobacteriosis analysed from national insurance claim data in Japan. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA347).
- Asakura T, Namkoong Ho, Suzuki S et al. Impact of six-minute walk test on health-related quality of life in pulmonary Mycobacterium avium complex disease. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA355).
- Kwan BS, Koh Y, Kim WS et al. Association between injectable aminoglycoside treatment duration and outcomes in cavitary Mycobacterium avium complex lung disease. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA538).
- Jacob M, Silva R, Gaio R et al. The effect of alcohol consumption in the treatment of nontuberculous mycobacteria. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA539).
- Boeck L, Skwark M, Pearson W et al. Late Breaking Abstract – Multidimensional genomic mapping reveals the pathophysiology of Mycobacterium abscessus. Programme and abstracts of the 2018 European Respiratory Society International Congress. Paris, France, 15–19 September 2018 (Abstract PA5450).