Clinical Features Associated with Linezolid Resistance Among Multidrug Resistant Tuberculosis Patients at a Tertiary Care Hospital in Mumbai, India

Abstract

Abstract 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.