4CPS-040 Interindividual variability of linezolid in critically ill patients

• Published in: European journal of hospital pharmacy. Science and practice 2022-03, Vol.29 (Suppl 1), p.A40-A41
• Main Authors: Guillen Martinez, O, Pomares Bernabeu, M, Gutierrez Palomo, S, Soriano Irigaray, L, Miralles Andreu, G, Navarro Ruiz, A
• Format: Article
• Language: English
• Subjects: Conflicts of interest; Patients; Pharmacokinetics; Section 4: Clinical pharmacy services
• ISSN: 2047-9956; 2047-9964
• DOI: 10.1136/ejhpharm-2022-eahp.85

Background and importanceA high variability in linezolid plasma concentrations (Cp) has been observed when administered at the standard dosage recommended in the technical data sheet (600 mg/12 hours), which is directly related to the effectiveness of the treatment and the appearance of haematological toxicity.Aim and objectivesThe main objective was to describe the Cp values of linezolid obtained in critically ill patients, as well as the recommendations made during pharmacokinetic monitoring.Material and methodsRetrospective observational study carried out in a third-level general hospital. Patients >18 years old admitted to the critical care units between September 2019 and May 2021,in which at least one Cp determination of linezolid was performed, were analysed. Demographic, clinical, therapeutic and pharmacokinetic monitoring-related variables were collected. Cp determination of linezolid was analysed by homogeneous enzyme immunoassay (IndikoTM Plus kit). The target therapeutic interval of linezolid was established between 2 and 8 µg/mL and statistical analysis was performed using R software.Results92 patients were analysed, 67% men and 33% women, with a median age of 67 and 68 years and a mean body mass index (BMI) of 30±7.74 kg/m2 and 30±6.98 kg/m2, respectively. Linezolid was administered intravenously (IV), 86 started treatment with the standard dosage (600 mg/12 hours), 5 with an intensified regimen (600 mg/8 hours) and only 1 patient with a regimen below that recommended in the technical data sheet (600 mg/24 hours). After the first control: 34 patients (37%) Cp = 2–8 µg/mL, 37 (40%) Cp 8 µg/mL. The median Cp at first control was 3.1 µg/mL, with a wide range of distribution (0.2 to 30 µg/mL). A modification of the dosage was recommended in 70% of the reports made and 47% achieved Cp within the therapeutic interval at the second control. A total of 2.4 determinations per patient were performed, recommending an individualised dosage in 60% of the reports. The recommended dosing was between 400 and 2400 mg/day, in intermittent infusion every 6, 8, 12 and 24 hours; and in 5 patients,1200–1800 mg/day by continuous infusion. A significant reduction in platelet count from baseline (>25%) was observed in 46% (42) patients and 22% (20) developed thrombocytopenia, with a platelet count below 100×103/µL.Conclusion and relevanceThere is high variability in the Cp of linezolid obtained in the critically ill patients analysed in our