Antimicrobial Drug Penetration is Enhanced by Lung Tissue Inflammation and Injury.

Pneumonia is a frequent and feared complication in intubated critically ill patients. Tissue concentrations of antimicrobial drugs need to be sufficiently high to treat the infection and also prevent development of bacterial resistance. It is uncertain whether pulmonary inflammation and injury affect antimicrobial drug penetration into lung tissue. To determine and compare tissue and bronchoalveolar lavage fluid concentrations of ceftaroline fosamil and linezolid in a model of unilateral acute lung injury in pigs and to evaluate if dose adjustment is necessary to reach sufficient antimicrobial concentrations in injured lung tissue. After induction of unilateral acute lung injury, ceftaroline fosamil and linezolid were administered intravenously. Drug concentrations were measured in lung tissue through microdialysis, and in blood and bronchoalveolar lavage fluid samples during the following 8 hours. The primary endpoint was the tissue concentration area under the curve in first 8 hours of the two antimicrobial drugs. In 10 pigs, antimicrobial drug concentrations were higher in inflamed and injured lung tissue compared to uninflamed and uninjured lung tissue (median ceftaroline fosamil AUC Tissue penetration of two commonly used antimicrobial drugs for pneumonia is enhanced by early lung tissue inflammation and injury, resulting in longer times above the minimal inhibitory concentration. Thus, lung tissue inflammation ameliorates antimicrobial drug penetration during the acute phase.