Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis - A pilot study

Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonos aeruginosa (Psa). Traditionally, aerosolized antibiotics are delivered by liquid nebu lization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially sa fe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intrav enously. The study was done according to a randomized, single-dose, and tri ple crossover protocol. Ten patients with CF or non-CF bronchiectasis and c hronically infected with Psa were recruited. Patients received a single dos e of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by i ntravenous infusion. In seven of the 10 patients, the minimum inhibitory co ncentration (MIC) was achieved in sputum after DPI and SVN, with mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 mu g/g sputum (range: 2.2 to 23.9 mu g/g) and 97.2 mu g/g sputum (r ange: 0.3 to 194.2 mu g/g), respectively, whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIG. Gentamicin given by DPI and SVN significantly decreased the sputum Psa density (p < 0 .05), by almost one order of magnitude. No significant decline in bacterial counts was observed after intravenous gentamicin. When gentamicin was inha led, blood concentrations were minimal, and were below concentrations known to cause systemic toxicity. For treatment of Psa infections susceptible to gentamicin, gentamicin administration by DPI appeared to be as efficient a s by SVN, despite the delivery of a 7-fold lower dose to the airways.