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

 

Abstract

Background

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.

Objectives

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.

Search strategy

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: 19 August 2008.

Selection criteria

All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic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

Data collection and analysis

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 As yet unpublished data were obtained for one of the included studies.

Main results

Thirteen 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, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16); % weight for height, MD -0.82 (95% CI -3.77 to 2.13); body mass index, MD 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, MD -8.20 (95% CI -15.32 to -1.08), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33).

Authors' conclusions

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.

 

Plain language summary

Giving aminoglycoside antibiotics intravenously once daily compared to giving them several times per day in people with cystic fibrosis

Cystic fibrosis is a serious genetic disorder which affects the lungs and the exocrine glands (sweat glands and others). Most people with cystic fibrosis develop persistent lung infections and they may receive frequent courses of intravenous antibiotics. Once-a-day doses reduce the cost and the time involved in giving the antibiotics, compared to several dose per day. This review includes four trials with a total of 328 people. All trials compared once-a-day dosing with three times-a-day dosing. The review found that giving the antibiotics once per day was just as good at treating lung infections in people with cystic fibrosis as the alternative treatment. Results suggest once daily treatment is less toxic to the kidneys in children, but may not be in adults. There were no differences between treatments for other outcomes. While once-daily treatment can be just as effective and more convenient than three-times daily treatment, we recommend further studies to look at the long-term safety of this treatment regimen.