• Jayesh A Dhanani, Sara Diab, Jivesh Chaudhary, Jeremy Cohen, Suzanne L Parker, Steven C Wallis, Clément Boidin, Adrian Barnett, Michelle Chew, Jason A Roberts, and John F Fraser.
• From the University of Queensland Centre for Clinical Research, Faculty of Medicine (J.A.D., J. Cohen, S.L.P., S.C.W., C.B., J.A.R.) Critical Care Research Group (J.A.D., S.D., J. Chaudhary, J.F.F.) Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy (J.A.R.), The University of Queensland, Brisbane, Australia Department of Intensive Care Medicine (J.A.D., J. Cohen, J.A.R.) Department of Pharmacy (J.A.R.), Royal Brisbane & Women's Hospital, Brisbane, Australia Institute of Health and Biomedical Innovation & School of Public Health and Social Work, Queensland University of Technology, Kelvin Grove, Brisbane, Australia (A.B.) Department of Anaesthesiology and Intensive Care, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden (M.C.) the Pierre Garraud Hospital, Civil Hospitals of Lyon, Lyon, France (C.B.) the National Center for Scientific Research 5558, Biometrics Laboratory and Evolutionary Biology, Claude Bernard University Lyon 1, Lyon, France (C.B.).
• Anesthesiology. 2019 Aug 1; 131 (2): 344-355.

BackgroundNebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs.MethodsTen anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h.ResultsThe peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001).ConclusionsCompared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.

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