Objective: 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.
Methods: 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.
Results: Median vancomycin lung tissue concentrations as well as penetration ratio were higher in inflamed and injured lungs compared to uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations as well as penetration were not different in inflamed and injured lungs compared to uninflamed and uninjured lungs (AUC0-6 P = 0.094 and AUCdialysate/AUCplasma ratio P = 0.173). Penetration ratio for both vancomycin and meropenem into epithelial lining fluid was not different between injured and uninjured lungs.
Conclusion: 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.
Keywords: Acute lung injury; Acute respiratory distress syndrome; Antimicrobial lung tissue penetration; Ventilator–associated pneumonia.
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