Impact of isoniazid monoresistance on overall and vulnerable patient populations in Taiwan.

Isoniazid is an early bactericidal anti-tuberculosis (TB) agent and isoniazid mono-resistance TB is the most prevalent drug-resistant TB worldwide. Concerns exist regarding whether resistance to isoniazid would lead to delayed culture conversion and worst outcomes. From January 2008 to November 2017, adult culture-positive pulmonary TB patients receiving isoniazid, rifampicin, pyrazinamide, and ethambutol were identified through Taiwan Center for Disease Control database and were followed until the end of 2017. Primary outcomes included time to sputum culture conversion (SCC) within two months. Secondary outcomes included death and unfavourable outcomes at the end of 2nd month. A total of 37,193 drug-susceptible and 2,832 isoniazid monoresistant pulmonary TB patients were identified. Compared with no resistance, isoniazid monoresistance was not associated with a delayed SCC (HR: 0.99, 95% CI: 0.94─1.05, p = 0.8145), a higher risk of 2-month mortality (HR: 1.19, 95% CI: 0.92─1.53, p = 0.1884), and unfavourable outcomes at 2nd month (OR: 1.05, 95% CI: 0.97─1.14, p = 0.2427). Isoniazid monoresistance was associated with delayed SCC (HR: 0.90, 95% CI: 0.83─0.98, p = 0.0099) and a higher risk of unfavourable outcomes (OR:1.18, 95% CI: 1.05─1.32, p = 0.0053) in patients aged between 20 and 65, and delayed SCC in patients without underlying comorbidities (HR: 0.90, 95% CI: 0.81─0.98, p = 0.0237). Isoniazid mono-resistant TB had a comparable outcome with drug-susceptible TB at the end of the intensive phase. Healthy, and non-elderly patients were more likely to had culture persistence, raising concerns about disease transmission in these subgroups and warranting early molecular testing for isoniazid resistance.