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, 4596 had isoniazid mono-resistance (high-level: 2279 [50.4%]; low-level: 2317 [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.