1. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.
- Author
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Hare KM, Grimwood K, Chang AB, Chatfield MD, Valery PC, Leach AJ, Smith-Vaughan HC, Morris PS, Byrnes CA, Torzillo PJ, and Cheng AC
- Subjects
- Anti-Bacterial Agents therapeutic use, Australia, Bacteria isolation & purification, Bacterial Infections drug therapy, Bronchiectasis complications, Carrier State microbiology, Child, Child, Preschool, Female, Humans, Infant, Macrolides therapeutic use, Male, New Zealand, Pacific Islands, Placebos administration & dosage, Population Groups, Anti-Bacterial Agents pharmacology, Azithromycin therapeutic use, Bacteria drug effects, Bacterial Infections microbiology, Drug Resistance, Bacterial, Macrolides pharmacology, Nasopharynx microbiology
- Abstract
Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.
- Published
- 2015
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