title: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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: 29 September 2011.
  
  
  METHODS
  All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic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.
  
  
  METHODS
  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 As yet unpublished data were obtained for one of the included studies.
  
  
  RESULTS
  Sixteen 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 0.33 (95% confidence interval -2.81 to 3.48); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33).
  
  
  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.
authors.affiliation: Department of Child Health, School of Clinical Sciences & Nottingham Respiratory BRU, University of Nottingham, Nottingham,UK. alan.smyth@nottingham.ac.uk
authors.forename: Alan R
authors.initials: AR
authors.lastname: Smyth
authors.forename: Jayesh
authors.initials: J
authors.lastname: Bhatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D016032:Randomized Controlled Trials as Topic; D014031:Tobramycin / Q000008:administration & dosage*; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D014031:Tobramycin