Mortality and Prognostic Factors of Nontuberculous Mycobacterial Infection in Korea:  A Population-Based Comparative Study

Abstract

Background: The burden of human infection with nontuberculous mycobacteria (NTM) is increasing worldwide. There is a great deal of research interest regarding the impact of NTM infection on global health. However, limited data exist on the mortality burden of NTM infection and the factors related to its mortality.

Methods: In this nationwide retrospective cohort study using the claims data from the Korean National Health Insurance, patients with NTM infection were identified using the International Classification of Disease, Tenth Revision code, and were one-to-one matched to tuberculosis (TB) infected patients and general controls .We compared demographic characteristics, underlying medical conditions, medication history, and survival probabilities among NTM, TB, and control groups. The survival probability of NTM infected patients was analyzed according to gender and age groups, and co-infected status with TB. Multivariable Cox proportional hazard regression analyses were conducted to identify factors related to mortality of NTM infected patients.

Findings: A total of 530,401 individuals were analyzed, including 183,267 patients with NTM infections, 166,666 with TB, and 180,468 controls. Overall, 16,325 (8·9%) of the NTM infected patients died during the study period. The overall 6-, 10- and 14-year cumulative survival probabilities in the NTM infection group were 86·3%, 80·8%, and 77·1%, respectively. These probabilities were all significantly lower than those of the TB and control groups (log-rank P <0.0001). In the case of patients co-infected with NTM and TB, the overall 6-, 10- and 14-year cumulative survival probabilities were 75·1%, 65·4%, and 57·0%, respectively. The survival probability of the NTM infected patients decreased with age, and was lower in men. Multivariable analysis indicated that old age, male, province, TB infection, obstructive lung disease, emphysema, interstitial pulmonary diseases, congestive heart failure, moderate or severe liver disease, diabetes with complications, paraplegia/hemiplegia, and renal disease were significantly associated with mortality in NTM infection. Additionally, the use of macrolide antibiotics (by more than one year) was significantly negatively correlated with mortality (adjusted hazard ratio [aHR] 0·61, 95% confidence interval [CI] 0·53-0·71), regardless of azithromycin (aHR 0·60, 95% CI 0·43-0·85) or clarithromycin use (aHR 0·63, 95% CI 0·53-0·75).

Interpretation: Patients with NTM infection had poor prognosis compared to TB or general population, especially in case of NTM and TB coinfection. Mortality of NTM infection was associated with certain demographic and clinical characteristics but, long-term use of macrolide may be associated with survival benefit.

Funding Statement: This study did not have any funding source.

Declaration of Interests: We declare no competing interests.

Ethics Approval Statement: The study protocol was approved by the Samsung Medical Center (IRB file no. 2019-01-144). The requirement for informed consent was waived due to the nature of the study. All data were anonymized to maintain confidentiality.