Aaron J Heffernan1, Fekade B Sime2, Jeffrey Lipman3, Jayesh Dhanani3, Katherine Andrews4, David Ellwood5, Keith Grimwood5, Jason A Roberts6. 1. School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia; Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia. 2. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland 4006, Australia. Electronic address: f.sime@uq.edu.au. 3. Faculty of Medicine, The University of Queensland, Brisbane, Queensland 4006, Australia. 4. Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia. 5. School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia; Gold Coast Health, Southport, Queensland 4215, Australia. 6. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland 4006, Australia.
Abstract
BACKGROUND: Knowledge of antibiotic concentrations achievable in the epithelial lining fluid (ELF) will help guide antibiotic dosing for treating patients with Gram-negative bacillary ventilator-associated pneumonia (VAP). OBJECTIVE: To compare: (1) the ELF:serum penetration ratio of antibiotics in patients with pneumonia, including VAP, with that in healthy study participants; and (2) the ELF and/or tracheal aspirate antibiotic concentrations following intravenous and nebuliser delivery. METHODS: Web of Science, EMBASE and PubMed databases were searched and a systematic review undertaken. RESULTS: Fifty-two studies were identified. ELF penetration ratios for aminoglycosides and most β-lactam antibiotics administered intravenously were between 0.12 and 0.57, whereas intravenous colistin may be undetectable in the ELF. In contrast, estimated mean fluoroquinolone ELF penetration ratios of up to 1.31 were achieved. Importantly, ELF penetration ratios appear reduced in critically ill patients with pneumonia compared with in healthy volunteers receiving intravenous ceftazidime, levofloxacin and fosfomycin; thus, dose adjustment is likely to be required in critically ill patients. In contrast to the systemic administration route, nebulisation of antibiotics achieves high ELF concentrations. Nebulised 400 mg twice-daily amikacin resulted in a median peak ELF steady-state concentration of 976.01 mg/L (interquartile range 410.3-2563.1 mg/L). Similarly, nebulised 1 million international units of colistin resulted in a peak ELF concentration of 6.73 mg/L (interquartile range 4.80-10.10 mg/L). CONCLUSION: Further pharmacokinetic studies investigating the mechanisms for ELF penetration in infected patients and healthy controls are needed to guide antibiotic dosing in VAP and to determine the potential benefits of nebulised therapy.
BACKGROUND: Knowledge of antibiotic concentrations achievable in the epithelial lining fluid (ELF) will help guide antibiotic dosing for treating patients with Gram-negative bacillary ventilator-associated pneumonia (VAP). OBJECTIVE: To compare: (1) the ELF:serum penetration ratio of antibiotics in patients with pneumonia, including VAP, with that in healthy study participants; and (2) the ELF and/or tracheal aspirate antibiotic concentrations following intravenous and nebuliser delivery. METHODS: Web of Science, EMBASE and PubMed databases were searched and a systematic review undertaken. RESULTS: Fifty-two studies were identified. ELF penetration ratios for aminoglycosides and most β-lactam antibiotics administered intravenously were between 0.12 and 0.57, whereas intravenous colistin may be undetectable in the ELF. In contrast, estimated mean fluoroquinolone ELF penetration ratios of up to 1.31 were achieved. Importantly, ELF penetration ratios appear reduced in critically illpatients with pneumonia compared with in healthy volunteers receiving intravenous ceftazidime, levofloxacin and fosfomycin; thus, dose adjustment is likely to be required in critically illpatients. In contrast to the systemic administration route, nebulisation of antibiotics achieves high ELF concentrations. Nebulised 400 mg twice-daily amikacin resulted in a median peak ELF steady-state concentration of 976.01 mg/L (interquartile range 410.3-2563.1 mg/L). Similarly, nebulised 1 million international units of colistin resulted in a peak ELF concentration of 6.73 mg/L (interquartile range 4.80-10.10 mg/L). CONCLUSION: Further pharmacokinetic studies investigating the mechanisms for ELF penetration in infectedpatients and healthy controls are needed to guide antibiotic dosing in VAP and to determine the potential benefits of nebulised therapy.
Authors: Mohammad H Al-Shaer; Michael N Neely; Jiajun Liu; Kartikeya Cherabuddi; Veena Venugopalan; Nathaniel J Rhodes; Kenneth Klinker; Marc H Scheetz; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2020-08-20 Impact factor: 5.191
Authors: Mohammad H Alshaer; Nicole Maranchick; Chen Bai; Kelly L Maguigan; Bethany Shoulders; Timothy W Felton; Sumith K Mathew; Mamoun T Mardini; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2022-06-14 Impact factor: 5.938
Authors: Aaron J Heffernan; Fekade B Sime; Nilesh Kumta; Steven C Wallis; Brett McWhinney; Jacobus Ungerer; Gloria Wong; Gavin M Joynt; Jeffrey Lipman; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2022-05-16 Impact factor: 5.938
Authors: N Layios; C Visée; V Mistretta; R Denooz; N Maes; J Descy; F Frippiat; S Marchand; N Grégoire Journal: Antimicrob Agents Chemother Date: 2022-01-31 Impact factor: 5.938
Authors: Michael Paal; Christina Scharf; Ann Katrin Denninger; Luis Ilia; Charlotte Kloft; Nikolaus Kneidinger; Uwe Liebchen; Sebastian Michel; Christian Schneider; Sebastian Schröpf; Carina Schuster; Michael Vogeser; Ferdinand Weinelt; Johannes Zander; Michael Zoller; Ines Schroeder Journal: Antimicrob Agents Chemother Date: 2021-09-27 Impact factor: 5.191