Incidence and risk factors of myelosuppression of linezolid in patients with drug-resistant tuberculosis: A scoping review

Abstract

Background: Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge, requiring prolonged treatment with multiple second-line anti-tuberculosis drugs. Among these medications, bedaquiline and linezolid have shown promising outcomes. However, the primary adverse effects of linezolid leading to dose reduction or early discontinuation is myelosuppression. Methods: This study involved a comprehensive review to evaluate the incidence and risk factors of linezolid-induced myelosuppressionin patients with DR-TB in bedaquiline-based regimens. Furthermore, the procedure adhered to the Systematic Reviews and Meta-Analyses (PRISMA) guideline for a scoping review. Results: The results showed that nine cohort studies met the inclusion criteria. Among the 3310 DR-TB patients in these studies, 661 (19.9%) had HIV. The incidence of myelosuppression ranged from 5.1% to 49.0%, with anemia being the most prevalent case, ranging from 2.9% to 39.0%. According to the reports, linezolid interruption, such as dose adjustments or complete discontinuation ranged from 20.5% to 23.6%. Myelosuppression occurred within a period less than three months on average. Several factors were identified as influencing myelosuppression (anemia) in DR-TB patients within these regimens, including age ≥ 60, concurrent treatment with zidovudine in HIV positive patients, and linezolid concentrations > 2 mg/L. No studies reported mortality cases associated with linezolid. Conclusions: The incidence of myelosuppression was relatively high in DR-TB patients with regimen containing linezolid. Anemia was the most prevalent symptom of myelosuppression during treatment, leading to early discontinuation of linezolid. It indicates that hematologic parameter should be closely supervised, especially in patients with risk factors during linezolid treatment.