Am. J. Respir. Crit. Care Med.,
Volume 160, Number 5, November 1999, 1711-1716
Dry Powder versus Intravenous and Nebulized
Gentamicin in Cystic Fibrosis and Bronchiectasis
A Pilot Study
N.
RENÉE CROWTHER LABIRIS,
ANNE M.
HOLBROOK,
HENRY
CHRYSTYN,
STUART M.
MACLEOD,
and
MICHAEL T.
NEWHOUSE*
Centre for Evaluation of Medicines, Father Sean O'Sullivan Research Centre and Barnett Medical Aerosol Research Laboratory,
McMaster University, Hamilton, Ontario, Canada; and School of Pharmacy, University of Bradford, United Kingdom
Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonas aeruginosa (Psa). Traditionally, aerosolized antibiotics
are delivered by liquid nebulization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially safe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intravenously. The study was done according to a
randomized, single-dose, and triple crossover protocol. Ten patients with CF or non-CF bronchiectasis and chronically infected with Psa were recruited. Patients received a single dose of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by intravenous infusion. In seven of the 10 patients, the minimum inhibitory concentration (MIC) was achieved in sputum after DPI and SVN, with
mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 µg/g
sputum (range: 2.2 to 23.9 µg/g) and 97.2 µg/g sputum (range: 0.3 to 194.2 µg/g), respectively,
whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIC.
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 inhaled, 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 as by SVN, despite the delivery of a 7-fold lower dose to the airways. Crowther Labiris NR, Holbrook AM, Chrystyn H,
Macleod SM, Newhouse MT. Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis: a pilot study.
