Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline

Abstract

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.

Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients

“…NTMs' susceptibility to standard antituberculosis (TB) drugs displays significant heterogeneity, standard anti-TB drug regimens being ineffective on NTM disease treatment [158]. Anti-NTM regimens are long (at least 18 months), and a 12 months period with sputum-negative results is required to confirm the cure [159,160]. Sputum-conversion, from a positive to negative finding of bacteria, is often difficult to achieve in NTM cases, especially for infection with macrolide-resistant NTM spp.…”

“…For patients with nonsevere MAC-pulmonary disease, the recommended initial therapy consists of a clarithromycin or azithromycin, ethambutol (ETB) and rifampicin (RIF) regimen. In the case of severe conditions, injectable amikacin or streptomycin is advised [159,160]. For clarithromycin-resistant MAC infections a regimen including RIF, ETB, either isoniazid (INH) or a quinolone, and an injectable aminoglycoside should be adopted [160].…”

“…M. kansasii has similar disease/ pathology presentation to pulmonary TB, a regimen with RIF, ETB, INH being recommended for drug-sensitive M. kansasii [159]. Alternatively, BTS (2017) recommends INH combined with pyridoxine, as an alternative to macrolides [160].…”

Differentialin vitroactivity of individual drugs and bedaquiline-rifabutin combinations against actively multiplying and nutrient-starvedMycobacterium abscessus

“…In the United States and around the world, there is mounting evidence that the prevalence of chronic lung disease caused by infections with Mycobacterium abscessus complex has been increasing (1–3). These infections, which primarily affect vulnerable populations with underlying lung conditions such as cystic fibrosis, are particularly difficult to treat, and the limited treatment options that exist are lengthy (1–2+ years in duration), associated with severe side effects, and curative only about 50% of the time (3–5). This dearth of effective treatment options is largely due to the intrinsic resistance of M. abscessus complex to most available antibacterials (2); therefore, it is imperative to thoroughly investigate the potential of drugs known to have activity against this complex.…”

“…In this study, we evaluated the activity of a panel of drugs against M. abscessus populations actively growing in nutrient-rich broth and against those that had been nutrient-starved in PBS for up to 14 days prior to drug exposure. All drugs evaluated (amikacin, bedaquiline, clarithromycin, clofazimine, imipenem, linezolid, and rifabutin) are either currently used for treatment of M. abscessus lung disease and/or are considered potentially active against M. abscessus based on preclinical studies (4, 5, 17–22). After an initial assessment of differential bactericidal activity of each drug alone, we then evaluated the bactericidal activity of bedaquiline and rifabutin combinations, with and without a third drug, amikacin, against actively growing and nutrient-starved M. abscessus populations.…”