Continuous infusion of time-dependent antibiotics: Lung pharmacokinetics and pharmacodynamics

Abstract

Lung infections continue to represent a significant burden to the healthcare system and improved antibiotic therapy may serve as a means to improve patient outcomes. Time-dependent antibiotics such as β-lactams and glycopeptides are commonly used as therapy for lung infections, and the emerging data suggest that administration by continuous infusion may result in improved patient outcomes. The aim of this review is to identify and analyze the published literature on lung penetration of time-dependent antibiotics administered by continuous infusion. Although only 16 relevant articles were identified during this structured review, data suggest that continuous infusion may have an important role in therapy for various lung infections. In acute lung injury, such as pneumonia, where local inflammation causes tight junctions between alveolar membrane epithelial cells to open, antibiotic penetration is significant. Continuous infusion of time-dependent antibiotics in these patients results in higher trough concentrations than bolus administration that optimizes the pharmacodynamic properties of these antibiotics. In chronic lung injuries, as evidenced in cystic fibrosis and chronic bronchitis, fibrotic scarring and the presence of thick mucus leads to highly variable but significantly reduced antibiotic penetration. In the presence of such pathology, continuous infusion of these antibiotics seems to normalize variable pharmacokinetic parameters as well as result in higher trough concentrations compared with bolus administration. Continuous infusion of time-dependent antibiotics seems to be a suitable method for optimizing antibiotic concentrations at the site of lung infections and as a result may lead to improved treatment success. © 2008 Lippincott Williams & Wilkins, Inc.