Objective:

To identify modifiable risk factors for acquired linezolid resistance, elucidate genotype-phenotype correlations across key resistance loci, and inform clinical decision-making regarding linezolid use in drug-resistant tuberculosis, emphasizing the importance of these factors in treatment outcomes.

Key Findings:

• Acquired linezolid resistance observed in 9%-15% of MDR-TB strains and up to 60% in XDR-TB cohorts, indicating a significant challenge for treatment.
• 50%-70% of LZD resistance linked to ribosomal gene mutations, which are critical for understanding resistance mechanisms.
• Non-ribosomal mechanisms, including efflux pump upregulation, also contribute to resistance, suggesting multiple pathways for therapeutic intervention.

Interpretation:

The study highlights the complexity of genotype-phenotype relationships in linezolid resistance and underscores the urgent need for improved understanding of clinical risk factors and standardized susceptibility testing to enhance treatment outcomes.

Limitations:

• Retrospective design may introduce bias; future studies should consider prospective designs.
• Lack of standardized phenotypic susceptibility testing limits data collection; advocating for standardized methods could improve data quality.
• Study conducted in a single center may affect generalizability; multi-center studies are recommended to validate findings.

Conclusion:

Understanding the mechanisms of linezolid resistance is crucial for optimizing treatment strategies in drug-resistant tuberculosis, particularly in resource-limited settings, and further research is needed to support these findings.