Feifan Xie1, Konstantinos Mantzarlis2, Polychronis Malliotakis3, Vasileios Koulouras4, Sophie Degroote5, Despoina Koulenti6,7, Stijn Blot6,8, Koen Boussery1, Jan Van Bocxlaer1, Pieter Colin1,9. 1. Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. 2. Department of Intensive Care, University Hospital of Larissa, University of Thessaly, Larissa, Greece. 3. Department of Intensive Care, University Hospital of Crete, Irakleio, Greece. 4. Department of Intensive Care, University Hospital of Ioannina, Ioannina, Greece. 5. General Internal Medicine, Infectious Diseases and Psychosomatic Medicine, Ghent University Hospital, Ghent, Belgium. 6. Burns, Trauma and Critical Care Research Centre, The University of Queensland, Centre for Clinical Research, Faculty of Medicine, Brisbane, Australia. 7. 2nd Critical Care Department, Attikon University Hospital, Athens, Greece. 8. Department of Internal Medicine, Ghent University, Ghent, Belgium. 9. University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands.
Abstract
OBJECTIVES: Altered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia. METHODS: Fifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA. RESULTS: A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old. CONCLUSIONS: Standard linezolid dosing is likely to provide insufficient target attainment against MRSA in obese patients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSA infections.
OBJECTIVES: Altered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obesepatients with pneumonia. METHODS: Fifteen obese pneumoniapatients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA. RESULTS: A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumoniapatients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old. CONCLUSIONS: Standard linezolid dosing is likely to provide insufficient target attainment against MRSA in obesepatients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSAinfections.
Authors: Alison L Blackman; Praneeth Jarugula; David P Nicolau; Sai Ho Chui; Manjari Joshi; Emily L Heil; Mathangi Gopalakrishnan Journal: Antimicrob Agents Chemother Date: 2021-01-20 Impact factor: 5.191
Authors: Philipp Simon; David Busse; David Petroff; Christoph Dorn; Lisa Ehmann; Sophie Hochstädt; Felix Girrbach; Arne Dietrich; Markus Zeitlinger; Frieder Kees; Charlotte Kloft; Hermann Wrigge Journal: J Clin Med Date: 2020-04-09 Impact factor: 4.241