We retrospectively analyzed patients who underwent SOT other than the lungs and subsequently developed NTM-PD during follow-up between January 2001 and December 2020 at Seoul National University Hospital, a tertiary referral hospital in South Korea. Because lung transplant recipients have an exceptionally high risk of developing NTM-PD due to structural lung disease or allograft exposure to NTM,8 we excluded patients who received lung transplantation in this study. All patients with NTM-PD satisfied the diagnostic criteria of the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America for NTM-PD.9

The demographic and clinical characteristics of the patients at the time of diagnosis of NTM-PD were collected, including age, sex, body mass index (BMI), type of organ transplantation (deceased/living donor; liver, kidney, heart, pancreas), the time between transplantation and NTM-PD diagnosis, identification of NTM species from respiratory specimens, drug susceptibility test results, radiographic findings based on chest computed tomography (CT), smoking history, and relevant comorbidities (interstitial lung disease, chronic obstructive pulmonary disease, myocardial infarction, chronic heart failure, diabetes mellitus, cerebrovascular disease, and malignancy). The regimen and duration of antibiotic treatment targeting the NTM-PD, if initiated, were also collected.

Baseline characteristics were summarized as counts and proportions for categorical variables and medians with interquartile ranges (IQRs) for continuous variables. To assess the impact of a previous history of SOT on the long-term survival of patients with NTM-PD, we performed a 1:20 propensity score-matched Kaplan–Meier analysis comparing the survival of the study population with that of patients who were diagnosed with NTM-PD between January 2007 and December 2020 at the same institution. Age, sex, BMI, the presence of cavitary lesion at the time of diagnosis of NTM-PD, having M. abscessus complex species versus other species as the causative species, initiation of treatment for NTM-PD, and the presence of comorbidities (interstitial lung disease, chronic obstructive pulmonary disease, myocardial infarction, chronic heart failure, diabetes mellitus, cerebrovascular disease, and malignancy) were matched and the log-rank test was utilized. Two-sided P values < 0.05 were considered statistically significant. All analyses were conducted using the R software (version 4.1.1; R Foundation for Statistical Computing, Vienna, Austria).

The present study protocol was reviewed and approved by the Institutional Review Board of the Seoul National University Hospital (approval No. H-2202-109-1303), and the requirement to obtain informed consent was waived owing to the retrospective and observational study design. This study was performed in accordance with the principles of the Declaration of Helsinki.

During the study period, 12 patients (median age, 64 years; IQR, 59–67 years; men, 66.7%) subsequently developed NTM-PD among a total of 4,685 SOT recipients (2,298 for kidney, 2,153 for liver, 200 for heart, and 34 for pancreas after or simultaneously with kidney). Seven (58.3%) and five (41.7%) patients underwent renal and liver transplantation, respectively. The median Model For End-Stage Liver Disease score of liver transplant recipients was 25. Nine out of 12 patients (6 for kidney and 3 for liver) received transplantation from deceased donors. The median time between transplantation and diagnosis of NTM-PD was 3.3 years (IQR, 1.5–10.8 years). Two patients (18.7%) developed NTM-PD within 1 year of transplantation. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.6 cases per 100,000 person-years among liver transplant recipients. One (8.3%) and three (25.0%) patients underwent desensitization or induction before transplantation, respectively. No one received thymoglobulin induction. Four (33.3%) patients received corticosteroid pulse therapy for the treatment of allograft rejection. At the time of NTM-PD diagnosis, tacrolimus was administered to 11 (91.7%) patients with a median trough level of 4.7 ng/mL (IQR, 4.1–5.9 ng/mL). Other than patient No. 9, whose mizoribine was stopped and tacrolimus was changed to sirolimus, no reduction or modification of immunosuppressant was made in other patients at the time of NTM-PD diagnosis. The detailed demographic and clinical characteristics of the study population are summarized in Table 1.

The most common mycobacterial species identified were M. avium (n = 6, 50.0%), followed by M. intracellulare (n = 3, 25.0%), M. abscessus subsp. abscessus (n = 1, 8.3%), M. abscessus subsp. bolletti (n = 1, 8.3%), and M. kansasii (n = 1, 8.3%). Most patients showed a nodular bronchiectatic pattern (n = 10, 83.3%), whereas two patients (16.7%) had cavitary lesions on chest CT. Detailed clinical information of each patient is presented in Table 2.

At the time of transplantation, chest radiographs showed no definite abnormalities in 8 patients (66.7%) and mild lung infiltration in 4 patients (33.3%). Among them, only one patient showed worsening of the existing lung infiltrates, whereas three patients developed new lesions in different lung regions. All sputum acid-fast bacilli tests were negative at the time of operation.

During a median follow-up of 4.2 (IQR, 2.3–8.8) years after the diagnosis of NTM-PD, antibiotic treatment was initiated in five (41.7%) patients with M. avium (4 patients) and M. intracellulare (1 patient) due to radiographic and/or symptomatic aggravation. The interval between NTM-PD diagnosis and treatment initiation was 1.3 (IQR, 0–1.8) years. Three patients received guideline-adhering therapy with clarithromycin, ethambutol, and either rifampicin or clofazimine, one patient (No. 5) received azithromycin monotherapy, and another patient (No. 7) was treated with a pulmonary TB regimen: isoniazid, rifampicin, ethambutol, and pyrazinamide. Culture conversion and microbiological cure were achieved in five (100%) and two (40%) patients, respectively. Both patients who underwent treatment not adhering to guidelines achieved culture conversion and patient No. 5 remained culture negative during treatment whereas patient No. 7 experienced recurrence after 14 months. Nonetheless, patient No. 7 was carefully observed without further treatment due to lack of symptomatic and radiographic aggravation.

During the study period, two patients died. One patient who received guideline-adhering NTM-PD therapy died of respiratory failure due to underlying idiopathic pulmonary fibrosis. The other patient who showed multiple cavitary lesions on chest CT with persistent fever and sputum was infected with M. kansasii. However, he was treated for suspected invasive pulmonary aspergillosis and necrotizing pneumonia. When retrospectively evaluated, NTM-PD was assumed to be the cause of death in this patient.

After propensity score-matching, every patient with a history of SOT was paired with 240 patients without a history of SOT. Characteristics and standard mean difference of the two groups are presented in Table 3. The overall survival between the two groups showed no statistical difference (log rank P value 0.62). The Kaplan–Meier survival plot is shown in Fig. 1.