Mycobacterium avium Complex: Addressing Gaps in Diagnosis and Management

Abstract

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria-which include clinical, radiological, and microbiologic criteria-should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens.

Keywords: diagnosis; pulmonary disease; refractory disease; risk factors; treatment.

Figure 1.

Annual isolation prevalence and disease prevalence per 100 000 persons of pulmonary nontuberculous mycobacteria, Ontario, Canada, 1998–2010 [10].

Figure 2.

Average annual age- and sex-specific incidence of pulmonary nontuberculous mycobacterial disease in Oregon, 2007–2012 [7]. Adapted with permission of the American Thoracic Society. Copyright 2020 American Thoracic Society. All rights reserved.

Figure 3.

Computed tomography scan from a 74-year-old woman with recurrent Mycobacterium avium complex (MAC) pulmonary disease. This thin woman has classic features of MAC pulmonary disease, including pectus excavatum and right middle lobe and lingula bronchiectasis with infiltrate.

Figure 4.

Treatment of Mycobacterium avium complex pulmonary disease. *Clarithromycin is an alternative. Abbreviations: Inh., inhaled; IV, intravenous; MAC, Mycobacterium avium complex.

Figure 5.

CONVERT study results for the primary outcome of negative sputum culture results with amikacin liposome inhalation suspension plus guideline-based therapy vs guideline-based therapy alone [48]. Abbreviations: ALIS, amikacin liposome inhalation suspension; CI, confidence interval; FDA, US Food and Drug Administration; GBT, guideline-based therapy; MIC, minimum inhibitory concentration; OR, odds ratio. Reprinted with permission of the American Thoracic Society. Copyright 2020 American Thoracic Society. All rights reserved.

Figure 6.

Research priorities for nontuberculous mycobacterial pulmonary infections. Abbreviations: IV, intravenous; NTM, nontuberculous mycobacteria.