Effect of Isoniazid Resistance on Treatment Outcome Among People With Pulmonary Tuberculosis in Korea

Background: Isoniazid resistance is the most common type of ant-tuberculosis drug resistance, which is often neglected in clinical practice. This study aimed to evaluate the impact of isoniazid mono-resistant tuberculosis (Hr-TB) on the treatment outcomes of people with pulmonary tuberculosis. Methods: People with pulmonary tuberculosis were enrolled from the Korea Tuberculosis Cohort (KTBC) registry and the multicenter prospective cohort study of pulmonary tuberculosis (COSMOTB). Isoniazid resistance was confirmed using drug susceptibility test results. The primary outcome was an unfavorable outcome, which defined as comprising death, failure, loss-to-follow-up, still-on-treatment, and not-evaluated. Logistic regression analysis was conducted to evaluate effect of isoniazid resistance on treatment outcomes. We also compared 2-month sputum negative culture conversion rate and incidence of adverse events between Hr-TB and drug-susceptible tuberculosis. Results: From the KTBC and COSMOTB databases, 10,482 and 758 participants were included, respectively. Compared to drug-susceptible tuberculosis, Hr-TB had higher rates of unfavorable outcome in the KTBC (45.8% vs. 37.0%, P < 0.001) and COSMOTB (31.5% vs. 17.9%, P = 0.014). Multivariable logistic regression analysis showed significant association between isoniazid resistance and unfavorable outcome in the KTBC (adjusted odds ratio [aOR], 1.43; 95% confidence interval [CI], 1.24–1.65) and in the COSMOTB (aOR, 1.98; 95% CI, 1.02–3.85). Additional analyses on COSMOTB data showed that Hr-TB had more serious adverse drug reactions, while 2-month sputum culture conversion rates did not differ significantly. Conclusion: Isoniazid resistance is significantly associated with unfavorable clinical outcomes.