Treatment Outcomes of High- and Low-Level Isoniazid-Resistant Tuberculosis: Analysis from A Nationwide Pulmonary Tuberculosis Cohort

OBJECTIVES: Isoniazid resistance is the most common first-line drug resistance in tuberculosis (TB) and is associated with poor outcomes when standard therapy is used. Whether different levels of resistance carry distinct prognostic implications remains unclear. METHODS: We identified patients with pulmonary isoniazid-mono-resistant TB (2008-2017) from the Taiwan Centers for Disease Control database and compared outcomes, including survival and time to culture conversion within, persistent sputum culture positivity at 7-12 months, and time to recurrence and acquired multidrug-resistance (MDR) within 2 years, between the high- and low-level resistance groups. RESULTS: Of 145,498 TB patients, 4,596 had isoniazid mono-resistance (high-level: 2,279 [50.4%]; low-level: 2,317 [49.6%]). Patients in the high-level resistance group more frequently received fluoroquinolones (30.9% vs. 23.2%, p<0.001), and injectable aminoglycosides (13.8% vs. 11.7%; p=0.027) for more than 80% of survivorship days in the first six months. Outcomes were similar between groups, except that high-level resistance was associated with persistent culture positivity at 7-12 months (adjusted OR: 1.24 [1.02-1.51]) and earlier progression to MDR-TB (adjusted HR: 3.00 [1.50-5.99]). CONCLUSIONS: High-level isoniazid mono-resistance was associated with delayed sputum culture conversion and an increased risk of acquired MDR, underscoring the need for rapid molecular detection.