Therapeutic Drug Monitoring of Linezolid in Drug-Resistant Tuberculosis Patients: Clinical Factors and Hematological Toxicities

耐药结核病患者利奈唑胺治疗药物监测:临床因素和血液学毒性

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Abstract

PURPOSE: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (C(max)), but the factors affecting linezolid C(max) and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid C(max) and investigate the association between linezolid concentration and hematological toxicity. PATIENTS AND METHODS: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid C(max) using chi-squared and binary logistic regression. The diagnostic utility of linezolid C(max) in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid C(max). Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the C(max). Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid C(max) for thrombocytopenia with an area under curve of 0.728. CONCLUSION: Suboptimal linezolid C(max) was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid C(max) increases the risk of thrombocytopenia. Meticulous monitoring of linezolid C(max) is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

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