Linezolid Dosing in Patients With Liver Cirrhosis: Standard Dosing Risk Toxicity
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- Sonia Luque
- Pharmacy Department, Parc de Salut Mar;
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- Rosana Muñoz-Bermudez
- Intensive Care Unit, Parc de Salut Mar;
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- Daniel Echeverría-Esnal
- Pharmacy Department, Parc de Salut Mar;
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- Luisa Sorli
- Institute Hospital del Mar d'Investigacions Mèdiques (IMIM);
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- Nuria Campillo
- Pharmacy Department, Parc de Salut Mar;
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- Javier Martínez-Casanova
- Pharmacy Department, Parc de Salut Mar;
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- Elena González-Colominas
- Pharmacy Department, Parc de Salut Mar;
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- Francisco Álvarez-Lerma
- Institute Hospital del Mar d'Investigacions Mèdiques (IMIM);
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- Juan Pablo Horcajada
- Institute Hospital del Mar d'Investigacions Mèdiques (IMIM);
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- Santiago Grau
- Pharmacy Department, Parc de Salut Mar;
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- Jason A. Roberts
- Departments of Intensive Care and Pharmacy, Royal Brisbane and Women's Hospital;
抄録
<jats:sec> <jats:title>Background:</jats:title> <jats:p>Limited data regarding altered linezolid pharmacokinetics in patients with liver cirrhosis are available. The objective of this study was to evaluate the pharmacokinetics, efficacy and safety of linezolid in cirrhotic patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>A case–control 1:1 study of patients undergoing linezolid therapeutic drug monitoring was conducted between January 2015 and June 2017. Cases with liver cirrhosis were matched with controls by age, body weight, comorbidities, renal function, and intensive care unit (ICU) admission.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Fifty-two patients were included, 26 in each group. Patients with Child–Pugh Scores A, B, and C were 1 (3.8%), 13 (50.0%), and 12 (46.2%), respectively. Cases had higher median linezolid trough plasma concentrations than controls [20.6 (17.4) versus 2.7 (11.3); <jats:italic toggle="yes">P</jats:italic> < 0.001)] and more frequently achieved an optimal pharmacodynamic index [26 (100%) versus 16 (61.5%); <jats:italic toggle="yes">P</jats:italic> = 0.002]. In addition, potentially toxic concentrations and treatment discontinuation due to overexposure and hematological toxicity were also more frequently seen in cirrhotic patients. Overall clinical cure rate was high (67.4%), and in-hospital mortality was 28.8%. No differences in clinical outcomes were observed between both groups.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Linezolid showed a high clinical cure rate. Nevertheless, plasma concentrations and treatment discontinuation due to hematological toxicity were higher in cirrhotic patients. Liver cirrhosis may influence linezolid pharmacokinetics and question the use of standard doses. Therapeutic drug monitoring of linezolid would be valuable in these patients.</jats:p> </jats:sec>
収録刊行物
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- Therapeutic Drug Monitoring
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Therapeutic Drug Monitoring 41 (6), 732-739, 2019-12
Ovid Technologies (Wolters Kluwer Health)