Twice vs three-times daily antibiotics in the treatment of pulmonary exacerbations of cystic fibrosis

Abstract

Background: Once daily dosing of aminoglycosides is widely used but is limited by the inconvenience of the slow infusion it requires and the associated three-times daily infusion of a beta-lactam. Twice daily tobramycin can be given as a slow IV bolus and may be more convenient. This study compares twice with three-times daily dosing of both tobramycin and ceftazidime.

Methods: This was a randomised, open-label, parallel group trial. CF patients presenting with an infective exacerbation were randomised to either twice or three-times daily ceftazidime and tobramycin. Markers of treatment efficacy and safety were measured in the two groups. The primary outcome measure was improvement in FEV1.

Results: 146 patients were randomised into the study. There was no significant difference in the two groups for improvement in FEV1% predicted (9.93% and 7.98% for twice daily and three-times daily respectively) and similar times to next exacerbation. There were no differences in the incidence of treatment failure, nephrotoxicity and ototoxicity.

Discussion: This study confirms that twice daily dosing of both tobramycin and ceftazidime is safe and effective and may be considered more convenient than current dosing schedules.