Abstract
BackgroundAcute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis.MethodsWe are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported.DiscussionTwo published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000326099
Highlights
Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants
Our retrospective review of 101 infants hospitalised with bronchiolitis at the Royal Darwin Hospital (Darwin, Northern Territory) found that 33.7% of Indigenous infants were readmitted within six-months of discharge from hospital[6]
Acute lower respiratory tract infections are the commonest cause of hospitalisation and potentially preventable deaths in Indigenous infants[4]
Summary
Study design We are conducting a parallel group, double-blind placebo RCT (with concealed allocation) to assess the impact of additional treatment with azithromycin in Indigenous infants admitted to two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with bronchiolitis. The primary and secondary outcome measures (see below) are monitored twice daily until the hospital admission’s end-point is reached (ready for respiratory discharge, defined as >16-hours without supplemental oxygen and infant is feeding well). We will analyse all clinical outcomes in the following pre-determined sub-groups: (i) age ≤ 6-months; and (ii) presence of bacterial respiratory pathogens that are resistant to macrolide antibiotics. The primary outcomes (LOS and duration of supplemental oxygen requirement) will be compared between infants receiving placebo or azithromycin using unpaired Student’s T-tests or Mann-Whitney tests (depending on normality of distribution). For Secondary Aim-3 (short-term impact of azithromycin on macrolide-resistance of pathogens in NPS cultures): the proportions of children with penicillinnon-susceptible S. pneumoniae and macrolide-resistant H. influenzae spp and M. catarrhalis before and after trial medications will be compared using ORs and 95% CI. Ethical approval The protocol has been granted full ethical approval from the respective Human Research Ethics Committees of all the participating institutions [Department of Health and Families (for Royal Darwin Hospital) and Menzies School of Health Research (Darwin), and the Townsville Hospital]
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