Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: A two-centre prospective interventional study

• Published in: International journal of antimicrobial agents Vol. 62; no. 2; p. 106881
• Main Authors: Shi, Lu, Zhang, Ying, Duan, Lufen, Huang, Lifeng, Li, Jingjing, Lu, Jian, Zhuang, Zhiwei, Yuan, Yunlong, Feng, Zongtai, Sun, Jiantong, Liu, Xin, Zhou, Qin, Xue, Hongzhi, Xu, Jinhui, Tang, Lian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2023
• Subjects: Anti-Bacterial Agents - adverse effects; Clinical pharmacist; Critical Illness - therapy; Humans; Intervention; Linezolid; Linezolid - adverse effects; Pharmacokinetics/pharmacodynamics; Population pharmacokinetic model; Prospective Studies; Retrospective Studies; Thrombocytopenia; Thrombocytopenia - chemically induced; Linezolid; Intervention; Thrombocytopenia; Population pharmacokinetic model; Clinical pharmacist; Pharmacokinetics/pharmacodynamics
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2023.106881

•Linezolid is an oxazolidinone antibiotic used to treat Gram-positive bacterial infections.•The most serious adverse drug reaction (ADR) is linezolid-induced thrombocytopenia (LIT).•Assessment of the value of pharmacist-led interventions on LIT incidence.•Population pharmacokinetic model can optimise the dosage regimen of linezolid.•Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. This study evaluated the intervention effect of clinical pharmacist-mediated optimisation of a linezolid regimen using a population pharmacokinetic (PPK) model. Patients treated with linezolid in two medical centres from January 2020 to June 2021 were retrospectively included in the control group; those treated from July 2021 to June 2022 were prospectively enrolled in the intervention group. Clinical pharmacists optimised the dosage regimen according to a published linezolid PPK model in the intervention group. An interrupted times series approach was used to analyse the data. The incidence of linezolid-induced thrombocytopenia (LIT), target attainment of pharmacokinetic/pharmacodynamic parameters and other adverse drug reactions (ADRs) were compared between the two groups. In total, 77 and 103 patients were enrolled in the control and intervention groups, respectively. The intervention group had a lower incidence of LIT and other ADRs than the control group (10.7% vs. 23.4%, P = 0.002; 1.0% vs. 7.8%, P = 0.027). The intervention group exhibited a considerably lower trough concentration (Cmin) and area under the concentration–time curve/MIC ratio (AUC24/MIC) (P = 0.001 and P < 0.001). Cmin and AUC24/MIC rates within the target range were substantially higher in the intervention group (49.6% vs. 20.0%, adjusted P < 0.05; 48.1% vs. 25.6%, adjusted P < 0.05). Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. Implementation of model-informed precision dosing (MIPD) for linezolid markedly increased the Cmin and AUC24/MIC rates within the target range. We recommend MIPD-guided linezolid dose reduction for patients with renal impairment. [Display omitted]