Isoniazid monoresistance in Taiwan

This study investigated the impact of isoniazid monoresistance on early treatment outcomes in patients with pulmonary tuberculosis (TB). Specifically, it aimed to determine whether resistance to isoniazid affects sputum culture conversion (SCC) and the likelihood of unfavourable outcomes within the first two months of treatment. Additionally, the researchers sought to identify which patient subgroups—especially those with isoniazid-resistant TB—might be at greater risk for poor outcomes, with the goal of informing more targeted interventions and closer monitoring strategies.

The researchers conducted a retrospective cohort study using data from Taiwan's CDC un-transitioned TB database, which was linked to national health insurance records for comprehensive patient information. The study included adults aged 20 years and older who were diagnosed with culture-positive pulmonary TB between 2008 and 2017 and received standard four-drug therapy for at least 14 days. Patients with resistance to other key drugs (rifampicin or ethambutol), prior exposure to second-line TB medications, those under 20 years old, or who died within the first month of treatment were excluded from the analysis.

In the main analysis of over 40,000 patients, isoniazid resistance—whether low-level or high-level—was not significantly associated with delays in SCC, persistent culture positivity after two months, early mortality, or other unfavourable outcomes. Key findings showed that 27.1% of patients did not achieve SCC by two months, 29.2% experienced an unfavourable outcome (death, loss to follow-up, or failure to convert), and 2.1% died within the first two months. Multivariable regression models consistently showed no significant impact of isoniazid resistance on these outcomes in the general cohort.

However, subgroup analyses revealed that isoniazid resistance may influence outcomes in certain populations. Among patients aged 20 to 65 and those without comorbidities, isoniazid resistance was associated with delayed SCC and higher odds of not achieving conversion within two months. These groups also had a modestly increased risk of experiencing unfavourable outcomes. More specifically, low-level isoniazid resistance was linked to delayed SCC in younger adults and higher early mortality in smear-positive patients, while high-level resistance was associated with delayed SCC in otherwise healthy individuals. Thus, while isoniazid monoresistance does not independently affect overall early treatment outcomes, certain subgroups may benefit from intensified care and closer follow-up.

Source: Lee, M.R., Keng, L.T., Lee, M.C., Chen, J.H., Lee, C.H. and Wang, J.Y., 2024. Impact of isoniazid monoresistance on overall and vulnerable patient populations in Taiwan. Emerging Microbes & Infections, 13(1), p.2417855.