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Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis
1Department of Child Health, E Floor East Block, Queens Medical Centre, Derby Road, Nottingham, UK, NG7 2UH.
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All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic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 As yet unpublished data were obtained for one of the included studies.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.
Insights
Once-daily aminoglycoside antibiotics are as effective as multiple daily doses for cystic fibrosis pulmonary exacerbations. Evidence suggests reduced nephrotoxicity in children with once-daily dosing.
Area of Science:
- Clinical Pharmacology
- Respiratory Medicine
- Infectious Diseases
Background:
- Cystic fibrosis (CF) patients often experience chronic Pseudomonas aeruginosa colonization.
- Pulmonary exacerbations in CF typically require intravenous aminoglycoside antibiotics.
- Aminoglycoside properties suggest potential for less frequent, higher-dose administration.
Purpose of the Study:
- To evaluate the efficacy and safety of once-daily versus multiple-daily intravenous aminoglycoside dosing.
- To assess treatment outcomes for pulmonary exacerbations in cystic fibrosis patients.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) comparing aminoglycoside dosing regimens in CF.
- Searched multiple databases and specialized registers up to August 19, 2008.
- Independent selection, quality assessment, and data extraction by two authors.
Main Results:
- Four RCTs involving 328 participants were included, comparing once-daily with thrice-daily aminoglycoside dosing.
- No significant differences observed in lung function (FEV1, FVC) or nutritional status between groups.
- Otoxicity incidence was similar; however, once-daily dosing showed reduced nephrotoxicity in pediatric patients.
Conclusions:
- Once-daily and multiple-daily aminoglycoside dosing demonstrate comparable efficacy for CF pulmonary exacerbations.
- Evidence supports a potential benefit of once-daily regimens in reducing nephrotoxicity, particularly in children.
- Further research may refine optimal aminoglycoside dosing strategies in cystic fibrosis management.
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