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Introduction: Pneumonia is a common bacterial infection and a serious complication in intubated critically ill patients. Ceftaroline fosamil, an antibiotic for the treatment of pneumonia needs to be in adequate tissue concentrations to effectively treat infections and prevent the development of bacterial resistance. However, it remains uncertain whether pulmonary inflammation and injury impact the penetration of the antibiotic into the lung tissue. 

Aim: This study aimed to investigate the pharmacokinetics of ceftaroline fosamil in plasma, lung tissue, and bronchoalveolar lavage fluid (BALF) in a porcine model with induced unilateral acute lung injury (ALI), utilizing a non-linear mixed-effects (NLME) modeling approach.

Method: Through a population pharmacokinetic modeling approach, drug concentrations of ceftaroline fosamil were explored in plasma, in injured and healthy lung tissue (using microdialysis) and in BALF samples over an 8-hour period. The area under the curve (AUC) of tissue concentration, as well as the peak concentrations of ceftaroline fosamil were derived from the models. 

Results: The findings revealed higher drug concentrations in injured lung tissue compared to healthy lung, with a median Cmax of 55.4 mg/L vs 34.7 mg/L and mean AUC0-6h of 0.45 vs 0.86, suggesting increased ceftaroline fosamil penetration in ALI.

Conclusion: This study highlighted an enhanced lung penetration of ceftaroline fosamil by acute tissue inflammation and injury. These insights contribute to a deeper understanding of antimicrobial drug behavior in ALI and support further evaluation of alternative dosing regimens. Further research is recommended to explore long-term effects and refine treatment strategies for pneumonia.