Severe Toxicity reported in MDR-TB patients with Linezolid >2mg/L, study finds.

A recent study revealed that >2mg/L concentrations of Linezolid are associated with the development of treatment-emergent toxicity in patients treated for Multi drug resistant Tuberculosis (MDR-TB). The study was published in the journal Clinical Infectious Diseases, 2022.

MDR-TB when treated with Linezolid is characterized by high rates of adverse events. The evidence on therapeutic drug monitoring to predict toxicity is scarce. Researchers conducted a study to evaluate the association of linezolid concentrations with severe toxicity.

The study was conducted between 2011 and 2017. It was a retrospective assessment of consecutive patients on Linezolid for MDR-TB. Severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation was the primary outcome. The impact of plasma linezolid trough concentrations >2 mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates.

The key findings of the study were:

• SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95%CI 0.30-0.49).
• A maximum linezolid trough concentration >2 mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2 mg/L in 22 (15%).
• The adjusted hazard ratio for SMT was 2.35 (95%CI 1.26–4.38, p = 0.01) in patients with a mean trough concentration >2 mg/L and 2.63 (95%CI 1.55–4.47, p < 0.01) for SMT after the first detection of a trough concentration >2 mg/L.
• In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering of elevated trough concentrations did not restore baseline risk.

Thus, the researchers concluded that Linezolid trough concentrations >2 mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR-TB. They further added that for any patient with trough concentrations above 2 mg/L an individual risk-benefit assessment on the continuation of linezolid treatment is warranted.  

For the Full Article, Click here: https://doi.org/10.1093/cid/ciac485