Effects of Lung Inflammation and Injury on Pulmonary Tissue Penetration of Meropenem and Vancomycin in a Model of Unilateral Lung Injury.

Timing and dosing of antimicrobial therapy is key in the treatment of pneumonia in critically ill patients. It is uncertain whether presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. We determined the effects of lung inflammation and injury on tissue penetration of two commonly used antimicrobial drugs for pneumonia in an established model of unilateral lung injury. In 13 healthy pigs, unilateral lung injury was induced in the left lung through cyclic rinsing - the right healthy lung served as control. After infusion of meropenem and vancomycin, lung tissue, blood, and epithelial lining fluid concentrations were monitored and compared over a period of 6 hours. Median vancomycin lung tissue concentrations as well as penetration ratio were higher in inflamed and injured lungs compared to uninflamed and uninjured lungs (AUC Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not detect impact of inflammation and injury.

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Competing Interests T.Stamm reports personal fees from AOP Health, AbbVie, Pfizer, Roche, and Takeda, outside the submitted work. All other authors declare no competing interests.