Delivery of topical antibiotics: pharmacokinetics and clinical problems

Despite major advances in new therapeutic agents to treat pneumonia, pneumonia remains a major cause of morbidity and mortality in hospitalized patients. Topical antibiotics offer many potential advantages in the treatment and prevention of nosocomial pneumonia. These include a high delivery of the drug to the site of infection and the potential for little systemic absorption and, as a result, reduced side effects. The potential disadvantages include failure of topical therapy to reach all diseased areas of the lung and the emergence of resistant organisms. Failure of many of the previous clinical studies has been ascribed to these potential disadvantages. However, little attention has been paid in previous clinical studies to actual dosage and regional distribution of aerosolized antibiotics in the lung and the pharmacokinetics of the aerosol after deposition. One major exception to this has been the use of aerosolized pentamidine, in which careful attention has been paid to nebulizer design, dosage to the lung, regional distribution, and pharmacokinetics. It should serve as the model for the testing of topical antibiotics therapy in the future.