Issues in antibiotic therapy for hospital-acquired and ventilator-associated pneumonia: emerging concepts to improve outcomes.

Introduction:Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) result in significant morbidity and mortality. The emergence of multi-drug resistant organisms has complicated the matter, as many of these pathogens now represent key causes of VAP and HAP. While anumber of new medications have been approved, acomprehensive appreciation of pharmacokinetic and pharmacodynamic principles, which, are often neglected, is key to effective treatment.Areas covered: The authors discuss the central pharmacokinetic and pharmacodynamic principles underlying antibiotic utilization, especially as they pertain to the treatment of VAP and HAP. They further address the concept of and implications of augmented renal clearance for the patient with nosocomial pneumonia. Finally, the authors review the evolving data on colistin and inhaled antibiotics in the management of pneumonia.Expert opinion: An enhanced understanding of the pharmacokinetic and pharmacodynamic principles along with insight into the concept of augmented renal clearance can help guide drug development and improve the way we currently dose and deliver most antibiotics. There is now mounting data on the limited efficacy and substantial nephrotoxicity of colistin, which makes it difficult to justify its continued use. While the concept of inhaled antibiotics is enticing, we lack conclusive data proving the efficacy of this paradigm.