<p>Association Between the Phenotype and Genotype of Isoniazid Resistance Among <em>Mycobacterium tuberculosis</em> Isolates in Thailand</p>

Purpose: The emergence of isoniazid-resistant tuberculosis (HR-TB) is a global public health problem, causing treatment failure and high mortality rates. This study aimed to determine the minimal inhibitory concentration (MIC) of isoniazid and detect the gene mutation in HR-TB and any association between the level of isoniazid resistance and gene mutation. Methods: We collected 74 clinical HR-TB isolates from two tertiary-care centers in Thailand. MICs were established using broth macrodilution. A line probe assay (LPA) was used to detect gene mutations that confer resistance to isoniazid, rifampicin, aminoglycosides, and fluoroquinolones. Results: Sixty-one (82.4%) isolates were monoresistant to isoniazid and 44 (72.1%) were highly resistant to isoniazid. From the clinical isolates, the range of isoniazid MICs was 0.4– 16 μg/mL. The katG S315T gene mutation was the prominent mutation in both isoniazid-monoresistant TB (70.5%) and multidrug-resistant TB (72.7%) isolates. The positive predictive value (PPV) of katG was 100% in detecting high levels of isoniazid resistance. The PPV of the inhA mutation was 93.8% in detecting low levels of isoniazid resistance. Five isolates (6.8%) exhibited low-level phenotypic resistance, whereas an LPA failed to detect an isoniazid gene mutation. Our study found one HR-TB isolate with a gyrA fluoroquinolone-resistant gene mutation. Conclusion: Most HR-TB isolates had high isoniazid-resistance levels associated with the katG gene mutation. High-dose isoniazid should be used with caution in patients with HR-TB. Early detection of drug resistance by genotypic assay can help determine an appropriate regimen. Keywords: tuberculosis, isoniazid, minimal inhibitory concentration, line probe assay, gene mutation