Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis

BMC Pharmacology and Toxicology

Research

Xiaoxi Liu¹  Sumika Osa¹  Kazuaki Matsumoto¹  Chihiro Ito¹  Kazuaki Taguchi¹  Yuki Enoki¹  Mari Aoki¹  Reika Saiki¹  Tomoya Nagai¹ 

[1] Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30, Shibakoen, Minato-ku, 105-8512, Tokyo, Japan;

关键词: Linezolid;    Hematological toxicity;    Thrombocytopenia;    Renal;    Trough concentrations;   

DOI  :  10.1186/s40360-022-00628-9

 received in 2021-11-16, accepted in 2022-11-16,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundLinezolid causes hematological toxicity, mostly thrombocytopenia, which leads to treatment discontinuation and failure. Recent studies revealed that during linezolid therapy, the incidence of treatment-related hematological toxicity is significantly higher in patients with decreased renal function (DRF) than in those with normal renal function. Linezolid monitoring is necessary due to the high frequency of hematological toxicity in patients with DRF and the relationship between blood concentration and safety. We performed a systematic review and meta-analysis to evaluate the safety correlation between DRF and trough monitoring.MethodsArticles published before June 24, 2022, on MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov were systematically analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method and the variable effects model.ResultsThe incidence of hematological toxicity was significantly higher in patients with DRF than in those without DRF (OR = 2.37; p < 0.001). Subgroup analysis, performed according to hematotoxicity classification, including thrombocytopenia, anemia, and pancytopenia, revealed a significantly higher incidence of thrombocytopenia (OR = 2.45; p < 0.001) and anemia (OR = 2.31; p = 0.006) in patients with DRF than in those without; pancytopenia (OR = 1.41; p = 0.80) incidences were not significantly higher. Based on a systematic review, linezolid trough concentrations > 6–7 μg/mL may be associated with an increased incidence of thrombocytopenia. However, no confidential threshold values for the development of thrombocytopenia were found in the area under the concentration curve values for children or adults.ConclusionWe observed a high frequency of hematological toxicity during linezolid therapy in patients with DRF. To ensure safety, linezolid trough concentrations should be ≤6–7 μg/mL.

【 授权许可】

CC BY   
© The Author(s) 2022

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