Optimal Antibiotic Therapy in the Management of the Lung of the Critically Ill

Pulmonary infections are very common in critically ill patients and are the source of significant morbidity and mortality. Early and appropriate antibiotic therapy is essential to maximise the likelihood of clinical success and decrease the development of antibiotic resistance from sub-optimal antibiotic concentrations. However, the altered physiology of critically ill patients can have significant effects on antibiotic concentrations at the site of infection. Antibiotics such as ??- lactams, aminoglycosides and glycopeptides may occasionally have elevated lung concentrations in some forms of acute lung injury, although not often within lung parenchyma, and certainly have decreased concentrations in patients with chronic lung injury (e.g., cystic fibrosis patients). For these antibiotics, high doses in the first 24-48 hours of treatment may be required to maximise penetration into the lung. Other antibiotics including fluoroquinolones, macrolides, tigecycline and linezolid will typically penetrate the lungs extensively and therefore will not require specific doses for critically ill patients with pulmonary infections. The purpose of this review article is to focus on the pharmacokinetic and pharmacodynamic principles of antibiotics in critically ill patients, with particular emphasis on optimising therapy for pulmonary infections.