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

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.

Keywords: Drug resistance; Drug susceptibility testing; India; Linezolid; MDR-TB.

Fig. 1

Observational Cohort Study Schema. Participants were recruited from a tertiary care chest clinic in Mumbai. Adults and adolescents with multidrug resistant tuberculosis (“MDR-TB,” resistant to rifampin and isoniazid) were recruited to an observational cohort. All participants with linezolid resistance test results available were included for analysis in this manuscript.

Fig. 2

Resistance to Anti-Tuberculosis Drugs by Linezolid Resistance Status. Rates of resistance to additional drugs on drug susceptibility testing by mycobacterial growth indicator tube identified frequent resistance to other drugs. Rates of resistance to amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide, and PAS were all statistically significantly different according to linezolid resistance status (p < 0.05).