title: Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.
abstract: 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. This is an update of a previously published review.
  
  
  
  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: 24 June 2016.
  
  
  
  All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic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.
  
  
  
  The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. 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 As yet unpublished data were obtained for one of the included studies.
  
  
  
  Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was no significant difference between treatment groups in: forced expiratory volume in one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48, moderate quality evidence); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16, low quality evidence); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13, low quality evidence); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42, low quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96, moderate quality evidence). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08, moderate quality evidence), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33, moderate quality evidence). The included trials did not report antibiotic resistance patterns or quality of life.
  
  
  
  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: Division of Child Health, Obstetrics & Gynaecology (COG), School of Medicine, University of Nottingham, Queens Medical Centre, Derby Road, Nottingham, UK, NG7 2UH.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Smyth
authors.affiliation: Paediatric Respiratory Medicine, Nottingham University Hospitals, QMC Campus, Derby Road, Nottingham, UK, NG7 2UH.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Bhatt
authors.affiliation: Department of Biostatistics, University of Liverpool, Block F, Waterhouse Building, 1-5 Brownlow Hill, Liverpool, UK, L69 3GL.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nevitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D016032:Randomized Controlled Trials as Topic; D014031:Tobramycin / Q000008:administration & dosage*; D014797:Vital Capacity / Q000187:drug effects; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D014031:Tobramycin