Nontuberculous Mycobacterial Disease in Solid-Organ Transplant Recipients and the General Population

Importance: Single-center studies suggest that solid-organ transplant recipients (SOTRs) with nontuberculous mycobacterial disease (NTM-D) face increased mortality, particularly in the presence of comorbidities such as chronic lung disease. Large-scale studies are needed to quantify the risk of NTM-D and its impact on mortality in this population. Objective: To compare the risk of NTM-D between the general population and SOTRs, stratified by lung and nonlung transplants, and to assess whether NTM-D is associated with increased mortality risk in SOTRs. Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada, from April 1, 2002, to December 31, 2018. Adult SOTRs were matched 1:10 with general population controls by age, sex, and region. Analyses were conducted from January 2024 to March 2025. Exposure: Solid-organ transplantation. Main Outcomes and Measures: The primary outcome was NTM-D, defined as isolation of NTM from blood, tissues, or respiratory samples (≥2 sputum cultures with the same species or 1 bronchoscopic or lung biopsy culture). The secondary outcome was all-cause mortality in the SOTR cohort at 1 year and by the end of follow-up (March 31, 2021). Cox proportional hazard models were used to estimate the risk of outcomes. Results: The study included 138 175 individuals (49 611 female [35.9%]; mean [SD] age, 51.87 [12.99] years), comprising 12 564 SOTRs (7674 kidney, 2419 liver, 1257 lung, 584 heart, 563 kidney-pancreas, and 67 multiorgan recipients) and 125 611 matched controls. During the study period, 368 SOTRs (2.92%) and 127 controls (0.10%) developed NTM-D. Receipt of a lung transplant (adjusted hazard ratio [aHR], 177.34; 95% CI, 79.65-394.82) or other solid-organ transplant (aHR, 8.89; 95% CI, 5.90-13.40) were both associated with increased risk of NTM-D compared with controls. NTM-D by Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) were associated with significant long-term mortality in lung SOTRs (MAC aHR, 1.66; 95% CI, 1.35-2.04; RGM aHR, 2.33; 95% CI, 1.59-3.39) and nonlung SOTRs (MAC aHR, 2.12; 95% CI, 1.36-3.29; RGM aHR, 2.25; 95% CI, 1.07-4.74). Conclusions and Relevance: In this cohort study of SOTRs and the general population, both lung transplantation and other solid-organ transplantation were associated with a significantly elevated risk of NTM-D, which was linked to a higher mortality risk. These findings highlight the need for preventive and screening strategies.