A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models

Intensive Care Medicine Experimental
Jayesh A DhananiJason A Roberts

Abstract

Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic. In vitro studies using a laser diffractometer and a bacterial-viral filter were used to measure the effect of the type and size of tracheal tubes and antibiotic concentration on the particle size distribution of the tobramycin 400 mg (4 ml; 100 mg/ml) and 160 mg (4 ml, 40 mg/ml) aerosol and nebulised mass delivered. To compare the regional drug distribution in the lung of two routes (intravenous and nebulised) of drug administration of tobramycin 400 mg, technetium-99m-labelled tobramycin 400 mg with planar nuclear medicine imaging was used in a mechanically ventilated ovine model. To measure tobramycin concentrations by intravenous and nebulised tobramycin 400 mg (4 ml, 100 mg/ml) administration in the lung interstitial space (ISF) fluid and ...Continue Reading

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Citations

Jun 11, 2020·American Journal of Respiratory and Critical Care Medicine·Frank L van de VeerdonkPaul E Verweij
Nov 12, 2020·Intensive Care Medicine·Charles-Edouard LuytJean-François Timsit
Feb 15, 2019·Molecular Pharmaceutics·Theerthankar DasHien T T Duong

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