Abstract
BACKGROUND: Nontuberculous mycobacterial (NTM) disease, predominantly caused by Mycobacterium avium complex (MAC), is an emerging global health concern. The evidence regarding MAC-specific mortality and causes of death remains limited. This study investigated mortality and causes of death among patients with MAC isolates. METHODS: A nationwide study in Denmark (1991-2018) included all patients with MAC isolates, excluding those identified using gastric lavages alone. Data from the International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, were linked with national registries. Patients were classified as having pulmonary (PMAC), extrapulmonary (EMAC), or disseminated MAC (DMAC) disease. Cumulative mortality rates were calculated, and adjusted hazard ratios (aHR) for mortality were estimated using Cox models, adjusting for age, sex, disease manifestation, and comorbidities. RESULTS: Among 2,027 patients, 1-year mortality rates were 19% (PMAC), 15% (EMAC), and 52% (DMAC), increasing to 68%, 22%, and 84% at 10 years, respectively. Mortality decreased over time, especially for EMAC and DMAC. The risk factors for higher mortality included older age (aHR 1.04), male sex (aHR 1.85), DMAC (aHR 2.66), and higher comorbidity (aHR 1.21). Over time, age-related mortality hazards increased (0.4%/year on average), while hazards related to EMAC (-9%/year), DMAC (-13%/year), and comorbidities (-1%/year) declined. Chronic respiratory disease and HIV were the leading causes of death. CONCLUSIONS: Despite improvements over nearly three decades, PMAC remains associated with substantial mortality. This study offers valuable insights into mortality trends and risk factors for MAC disease, providing findings that can assist clinicians in delivering more accurate prognoses for different patient groups.