• Cristiane Luchesi de Mello Morais, Nascimento Jorge Willian Leandro JWL, Aline Corrêa Ribeiro, Luis Ignacio Cortinez, Carmona Maria José Carvalho MJC, Débora Rothstein Ramos Maia, Antoine Monsel, Auler José Otavio Costa JOC Jr, Jean-Jacques Rouby, and Denise Aya Otsuki.
• From the Laboratory of Anesthesiology, School of Medicine, São Paulo University, São Paulo, Brazil (C.L.d.M.M., M.J.C.C., D.R.R.M., J.O.C.A., D.A.O.) Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil (J.W.L.N., A.C.R.) Anesthesiology Division, School of Medicine, Pontifical Catholic University of Chile, Santiago de Chile, Chile (L.I.C.) Sorbonne University, Multidisciplinary Intensive Care Unit, Pitié-Salpêtrière Hospital, Public Assistance Hospitals of Paris, Paris, France (A.M., J.-J.R.).
• Anesthesiology. 2020 Jun 1; 132 (6): 1516-1527.

BackgroundIntravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets.MethodsTwelve female piglets received a single intravenous dose of vancomycin (15 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of administration. Twelve piglets received a single nebulized dose of vancomycin (37.5 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of the aerosol administration. In each group, vancomycin lung tissue concentrations were assessed on postmortem lung specimens using high-performance liquid chromatography. Blood samples were collected for serum vancomycin concentration measurement 30 min and 1, 2, 4, 6, 8, and 12 h after the end of vancomycin administration. Pharmacokinetics was analyzed by nonlinear mixed effect modeling.ResultsOne hour after vancomycin administration, lung tissue concentrations in the aerosol group were 13 times the concentrations in the intravenous group (median and interquartile range: 161 [71, 301] μg/g versus 12 [4, 42] μg/g; P < 0.0001). Twelve hours after vancomycin administration, lung tissue concentrations in the aerosol group were 63 (23, 119) μg/g and 0 (0, 19) μg/g in the intravenous group (P < 0.0001). A two-compartment weight-scaled allometric model with first-order absorption and elimination best fit serum pharmacokinetics after both routes of administration. Area under the time-concentration curve from 0 to 12 h was lower in the aerosol group in comparison to the intravenous group (56 [8, 70] mg · h · l vs. 121 [103, 149] mg · h · l, P = 0.002). Using a population model, vancomycin bioavailability was 13% (95% CI, 6 to 69; coefficient of variation = 85%) and absorption rate was slow (absorption half life = 0.3 h).ConclusionsAdministration of vancomycin by nebulization resulted in higher lung tissue concentrations than the intravenous route.

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