Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/11306
Title: Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial.
Authors: Goyal, Vikas
Grimwood, Keith
Byrnes, Catherine A
Morris, Peter S
Masters, I Brent
Ware, Robert S
McCallum, Gabrielle B
Binks, Michael J
Marchant, Julie M
van Asperen, Peter
O'Grady, Kerry-Ann F
Champion, Anita
Buntain, Helen M
Petsky, Helen
Torzillo, Paul J
Chang, Anne B
Affiliation: Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD, Australia; School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Centre for Children's Health Research, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: drvikasgoyal@gmail.com..
School of Medicine, Griffith University, Gold Coast, QLD, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia; Department of Infectious Diseases, Gold Coast Health, Gold Coast, QLD, Australia; Department of Paediatrics, Gold Coast Health, Gold Coast, QLD, Australia..
Department of Paediatrics, University of Auckland, Auckland, New Zealand; Respiratory Department, Starship Children's Hospital, Auckland, New Zealand..
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Department of Paediatrics, Royal Darwin Hospital, Darwin, NT, Australia..
Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD, Australia; School of Medicine, The University of Queensland, Brisbane, QLD, Australia..
Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia..
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia..
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia..
Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD, Australia; School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Centre for Children's Health Research, Queensland University of Technology, Brisbane, QLD, Australia..
Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia..
Centre for Children's Health Research, Queensland University of Technology, Brisbane, QLD, Australia..
Pharmacy Department, Lady Cilento Children's Hospital, Brisbane, QLD, Australia..
Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD, Australia..
Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia; School of Nursing and Midwifery, Griffith University, Gold Coast, QLD, Australia..
Central Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia..
Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD, Australia; Centre for Children's Health Research, Queensland University of Technology, Brisbane, QLD, Australia; Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia..
Issue Date: 6-Oct-2018
Citation: Lancet (London, England) 2018-10-06; 392(10154): 1197-1206
Abstract: Although amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis. We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897). We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed non-inferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5). By 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance. Australian National Health and Medical Research Council.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/11306
DOI: 10.1016/S0140-6736(18)31723-9
Type: Journal Article
Appears in Collections:NT Health digital library

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