Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis

People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often.

To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis.

We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: August 2005.

All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy and/or toxicity, in people with cystic fibrosis.

The two authors independently selected the studies to be included in the review and assessed methodological quality of each study. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies.

Eleven studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants were included in this review. All studies compared once-daily dosing with thrice-daily dosing. There was no significant difference between treatment groups in: forced expiratory volume at one second, weighted mean difference (WMD) 0.33 (95% confidence interval (CI) -2.81 to 3.48); forced vital capacity, WMD 0.29 (95% CI -6.58 to 7.16); % weight for height, WMD -0.82 (95% CI -3.77 to 2.13); body mass index, WMD 0.00 (95% CI -0.42 to 0.42); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96). The percentage change in creatinine significantly favoured once-daily treatment in children, WMD -8.20 (95% CI -15.32 to -1.08), but showed no difference in adults, WMD 3.25 (95% CI -1.82 to 8.33).

Once and three times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.