C106-25 Treatment Outcomes and Adverse Events in Nontuberculous Mycobacterial Disease Patients: A Prospective, Longitudinal, Multicenter Study From India

Abstract Rationale Sparse published nationwide data from India, very few global longitudinal studies are available regarding treatment outcomes of nontuberculous mycobacterial (NTM) disease. Methods In this prospective observational study (2021-2025), culture-confirmed NTM-pulmonary disease [NTM-PD] and extrapulmonary-NTM disease [EP-NTM] patients ≥12 years of age, irrespective of their HIV status, after obtaining informed consent, were included. Patients with concurrent active TB were excluded. NTM species/subspecies identification was performed using line probe assay and validated by whole-genome sequencing. Baseline laboratory testing included serum vitamins D3, B12. Counselling on treatment duration, adverse events, and compliance was done before species-specific treatment initiation as per ATS/IDSA/ERS/ESCMID 2020 guidelines. Clinical, radiological, microbiological, and adverse-event monitoring was conducted during follow-up every 1-2 months. Free treatment was provided from project funds; telephonic or home visit follow-up was done if hospital access was limited. Slowly growing mycobacteria received macrolides with ethambutol and rifampicin; severe disease or rapidly growing mycobacteria (RGM) required intensification with parenteral amikacin and linezolid/clofazimine. Results One hundred and fifty-five patients (mean age 44.4[SD:15.2] years; 92[59.4%] males; NTM-PD 123, EP-NTM 32) were initiated on treatment. Key risk factors for NTM-PD included prior pulmonary TB [96.8%], malnutrition [47.1%], bronchiectasis [23.8%], and COPD [19.3%]. Most common species identified: M.avium complex (44/155;28.4%), M.abscessus complex [44/155;28.4%], and M.kansasii [23/155;14.8%]. Mean time from symptom onset to seeking healthcare was 92.1 days [SD:44.1] and interval from first healthcare contact to species/subspecies-level diagnosis was 120 [SD:50] days; overall diagnostic delay was 212.4 days [SD:38]. Of the 155, 137 [88.4%] patients completed treatment, 9 [5.8%] died, and another 9 [5.8%] were lost to follow-up. Treatment completion, death, and loss-to-follow-up were 110/123 [89.4%], 5/123 [4.1%], and 8/123 [6.5%] for NTM-PD versus 27/32 [84.4%], 4/32 [12.5%], and 1/32 [3.1%] for EP-NTM, respectively [P = 0.15]. Mean time-to-culture conversion in NTM-PD was 94.3[SD:42.6] days. Three-drug regimen was most frequently used (3 vs 4 vs 5 drugs: 127/155 [82.0%], 27/155 [17.4%], 1/155 [0.7%]), with four-drug use administered in severe NTM-PD or RGM. Mean treatment duration was 550.5[SD:94.3] days for NTM-PD and 237.3[SD:115.5] days for EP-NTM. Common adverse effects included: gastrointestinal disturbance [68.4%]; hepatotoxicity [14.8%]; tinnitus [1.9%]; optic neuritis [1.3%]; thrombocytopenia [1.3%]. Tinnitus (n = 2; amikacin alone; amikacin plus linezolid) and optic neuritis (ethambutol plus linezolid) resolved quickly after drug-discontinuation. One patient with tigecycline-induced thrombocytopenia died from other comorbidities; linezolid-induced thrombocytopenia in another patient reversed after drug-discontinuation. Conclusions Early diagnosis up to species/subspecies-level (where indicated), structured follow-up, judicious use of guideline-based regimen facilitate good treatment outcomes. This abstract is funded by: Indian Council of Medical Research (ICMR), New Delhi, India,Department of Health Research, Ministry of Health & Family Welfare, Government of India (Project file no: no.5/8/5/41/ITRC/2018/ECD-I)