The Management of Linezolid-Induced Adverse Events in Shorter and Longer Treatment of Rifampicin-Resistant Tuberculosis.

Abstract

Background: Linezolid is included in most of the regimens for treatment of rifampicin-resistant tuberculosis. The prior publications presented the safety profile and clinical effectiveness of linezolid.

Objectives: The research objectives of this study include: description of cumulative incidence rates of linezolid-induced adverse events, assessment of associations of those events with different variables, evaluation of the adverse event management and impacts of the unfavorable events on the effectiveness of treatment for rifampicin-resistant tuberculosis.

Methods: We analyzed and compared the data of 2 cohorts: the retrospective cohort of the longer treatment regimens, and the prospective longitudinal cohort consisting of patients on the shorter regimens. Systematic collection of data on adverse events was conducted according to the principles of active pharmacovigilance.

Results: The most common linezolid-induced adverse event was peripheral neuropathy (17.5%, 95% confidence interval [CI]: 9.2-25.8). Developing peripheral neuropathy was associated with comorbidities (HIV and endocrine disorders) and the age above 56. The patients exposed to the combination of linezolid and cycloserine were at higher risk of peripheral neuropathy compared with the patients receiving only one of those drugs. The mean time to recovery from peripheral neuropathy was 5.5 months. Myelosuppression and optic nerve disorders were observed at a relatively low frequency.

Conclusion and relevance: The rational management of linezolid-induced adverse events minimizes their impact on the effectiveness of treatment. The timely withdrawal of linezolid is the most rational way to prevent delayed recovery from peripheral neuropathy. The withdrawal of linezolid during the first 4 months of chemotherapy was associated with the failure to complete the shorter regimens in 9 months because of slow radiological dynamics. In our research, we are the first to assess the safety and effectiveness of the mSTR regimens in the context of linezolid-induced adverse events by comparing the findings with the data of conventional treatment.