T W Felton1,2, K Ogungbenro3, E Boselli4, W W Hope5, K A Rodvold6. 1. Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK. 2. Acute Intensive Care Unit, Manchester University NHS Foundation Trust, Manchester, UK. 3. Division of Pharmacy and Optometry, The University of Manchester, Manchester, UK. 4. APCSe UPSP 2016.A101, VetAgro Sup, University Lyon I Claude Bernard, University of Lyon, Lyon, France. 5. Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. 6. College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Abstract
Background: Severe infections of the respiratory tracts of critically ill patients are common and associated with excess morbidity and mortality. Piperacillin is commonly used to treat pulmonary infections in critically ill patients. Adequate antibiotic concentration in the epithelial lining fluid (ELF) of the lung is essential for successful treatment of pulmonary infection. Objectives: To compare piperacillin pharmacokinetics/pharmacodynamics in the serum and ELF of healthy volunteers and critically ill patients. Methods: Piperacillin concentrations in the serum and ELF of healthy volunteers and critically ill patients were compared using population methodologies. Results: Median piperacillin exposure was significantly higher in the serum and the ELF of critically ill patients compared with healthy volunteers. The IQR for serum piperacillin exposure in critically ill patients was six times greater than for healthy volunteers. The IQR for piperacillin exposure in the ELF of critically ill patients was four times greater than for healthy volunteers. The median pulmonary piperacillin penetration ratio was 0.31 in healthy volunteers and 0.54 in critically ill patients. Conclusions: Greater variability in serum and ELF piperacillin concentrations is observed in critically ill patients compared with healthy adult subjects and must be considered in the development of dosage regimens. Pulmonary penetration of antimicrobial agents should be studied in critically ill patients, as well as healthy volunteers, during drug development to ensure appropriate dosing of patients with pneumonia.
Background: Severe infections of the respiratory tracts of critically illpatients are common and associated with excess morbidity and mortality. Piperacillin is commonly used to treat pulmonary infections in critically illpatients. Adequate antibiotic concentration in the epithelial lining fluid (ELF) of the lung is essential for successful treatment of pulmonary infection. Objectives: To compare piperacillin pharmacokinetics/pharmacodynamics in the serum and ELF of healthy volunteers and critically illpatients. Methods:Piperacillin concentrations in the serum and ELF of healthy volunteers and critically illpatients were compared using population methodologies. Results: Median piperacillin exposure was significantly higher in the serum and the ELF of critically illpatients compared with healthy volunteers. The IQR for serum piperacillin exposure in critically illpatients was six times greater than for healthy volunteers. The IQR for piperacillin exposure in the ELF of critically illpatients was four times greater than for healthy volunteers. The median pulmonary piperacillin penetration ratio was 0.31 in healthy volunteers and 0.54 in critically illpatients. Conclusions: Greater variability in serum and ELF piperacillin concentrations is observed in critically illpatients compared with healthy adult subjects and must be considered in the development of dosage regimens. Pulmonary penetration of antimicrobial agents should be studied in critically illpatients, as well as healthy volunteers, during drug development to ensure appropriate dosing of patients with pneumonia.
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