Abstract Rationale The coexistence of Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) and chronic pulmonary aspergillosis (CPA) poses major clinical challenges due to overlapping radiologic features and conflicting treatment priorities. Antifungal therapy is often deferred because of concerns about adverse events and drug-drug interactions (DDIs) between azoles and rifamycin-based NTM-PD regimens. This study examined how microbiologic and serologic findings influence antifungal treatment decisions and how azole initiation affects concurrent NTM-PD therapy. Methods We retrospectively reviewed patients with NTM-PD who showed evidence of Aspergillus infection—positive Aspergillus antigen, anti-Aspergillus IgG antibody, or isolation of Aspergillus species from respiratory cultures—treated at our hospital between January 2024 and August 2025. Clinical characteristics, diagnostic test results, antifungal initiation, and modifications of NTM regimens were analyzed. Results Thirty-three patients met inclusion criteria. The median age was 76 years (range, 50-88), and 24 (73%) were women. Nineteen and 14 patients had nodular-bronchiectatic and cavitary diseases, respectively. Detected causative NTM species were Mycobacterium avium (n = 20), M. intracellulare (n = 10), M. kansasii (n = 1), M. septicum (n = 1), and mixed infection (n = 1). Twelve patients (36%) had malignancies and four (12%) received immunosuppressive therapy. Among 21 culture-positive cases, Aspergillus fumigatus was identified in 11 and A. niger in 8. Serum anti-Aspergillus IgG was positive in 8 patients (24%), whereas Aspergillus antigen was positive in 19 (58%), indicating discordance between serologic and antigen-based findings. Antifungal therapy was initiated in 7 patients (21%), all of whom were anti-Aspergillus IgG positive; none with antigen or culture positivity alone received antifungals, suggesting clinicians relied on serological evaluation to initiate appropriate treatment. Of these, 5 had cavitary and 2 had nodular-bronchiectatic disease. Azoles used were isavuconazole (n = 4), voriconazole (n = 2), and itraconazole (n = 1). Before antifungal initiation, 4 patients received rifampicin-containing NTM regimens; after azole introduction, NTM therapy was discontinued in 3 and modified in 1 to a rifamycin-sparing regimen. Two patients developed neuropsychiatric symptoms during azole therapy but were successfully switched to alternative agents. Conclusions In this real-world cohort of NTM-PD, antifungal therapy was initiated mainly in patients with positive anti-Aspergillus IgG, whereas antigen or culture positivity alone rarely prompted treatment. Clinicians appeared to require highly specific serologic evidence before interrupting standard NTM therapy, likely reflecting concerns about DDIs and regimen complexity. Understanding these diagnostic and therapeutic thresholds may guide future strategies to optimize antifungal-antimycobacterial co-management and improve outcomes in this challenging overlap condition. This abstract is funded by: None
Kamimoto et al. (Fri,) studied this question.