Clinical features associated with linezolid resistance among multidrug resistant tuberculosis patients at a tertiary care hospital in Mumbai, India

Background: Multidrug-resistant tuberculosis (MDR-TB) is an increasing problem worldwide, and 24% occurs in India. Linezolid is associated with improved MDR-TB treatment outcomes but causes significant side-effects and drug susceptibility testing (DST) is rarely available. This study assessed whether clinical factors could predict linezolid resistance. Methods: An observational cohort of adults and adolescents with MDR-TB at a tertiary care hospital in Mumbai, India was analyzed for clinical, laboratory, and radiographic findings associated with linezolid resistance. Results: In total, 343 MDR-TB patients had linezolid DST performed, and 23 (6.7%) had linezolid-resistant MDR-TB. Univariable analysis associated linezolid resistance with underweight (odds ratio (OR)–1.07, 95% confidence interval (CI):1.01–1.12); number of previous providers (OR:1.03, 95% CI:1.00–1.05); previous treatment with linezolid (OR:1.12, 95% CI:1.06–1.05), bedaquiline (OR:1.55, 95% CI:1.22–1.98), or clofazimine (OR:1.08 95% CI:1.03–1.16); cavitary disease (OR:1.10, 95% CI:1.04–1.16) and percent lung involvement (OR:1.02, 95% CI:1.01–1.03) on radiograph. DST associated linezolid resistance with resistance to fluoroquinolones (OR:1.08, 95% CI:1.01–1.14), injectables (OR:1.09, 95% CI:1.03–1.15), ethionamide (OR:1.09, 95% CI:1.03–1.15), and PAS (OR:1.13, 95% CI:1.06–1.21). In multivariate analysis, only prior linezolid and percent lung involvement were associated with linezolid resistance. Conclusion: To maximize treatment benefits while minimizing toxicity, DST remains an important tool to identify linezolid resistance.