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

BackgroundOnce 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.MethodsThis 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.Results146 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.DiscussionThis 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.