Al-Aloul M, Nazareth D, Walshaw M et al.
Liverpool Heart and Chest Hospital NHS Trust, Liverpool, UK.
J Aerosol Med Pulm Drug Deliv 2013 Nov 12; Epub ahead of print.
Aleksandra Norek’s review: The improving survival rates in patients with cystic fibrosis (CF) have brought new complications, either as unexpected manifestations of the CF condition or as a consequence of a lifetime of necessary aggressive treatment regimens. One such recognized complication in older CF patients is renal disease. Repeated administration of intravenous aminoglycosides, which are highly effective agents against Pseudomonas aeruginosa infection, is associated with cumulative nephrotoxicity. Nebulized formulations of tobramycin that have excellent deposition rates in the lung and higher levels in sputum than the intravenous preparation, but have low systemic bioavailability (12%), are now available for the prophylactic suppression of P aeruginosa infection in CF patients; however, their use to treat acute exacerbations has not been investigated to date.
The aim of the current randomized, crossover, 14-day pilot study was to compare the effect of intravenous tobramycin (mean total daily dose 8.2 mg/kg in two or three separate doses) with nebulized tobramycin (TNS; Chiron Corporation Ltd., Uxbridge, UK; 300 mg twice daily) administered using a Pari LC Plus™ jet nebulizer (Pari Medical Ltd., West Byfleet, UK) and a Porta-Neb® compressor (Medic-Aid Ltd., Bognor Regis, UK) in 20 CF adults who were chronically infected with P aeruginosa. Patients also received intravenous colistimethate sodium (Forest Laboratories Ltd., Dartford, UK) in both arms of the study. The efficacy endpoints were change in percent of predicted forced expiratory volume in 1s (FEV1) from baseline to day 14, reduction in sputum P aeruginosa density over the same period, and time to next exacerbation.