caa a22 4500 606158065 CHVBK 20210128100617.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s10096-015-2480-0 doi (NATIONALLICENCE)springer-10.1007/s10096-015-2480-0 Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo [Elektronische Daten] [K. Hare, K. Grimwood, A. Chang, M. Chatfield, P. Valery, A. Leach, H. Smith-Vaughan, P. Morris, C. Byrnes, P. Torzillo, A. Cheng] 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 (30mg/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. Springer-Verlag Berlin Heidelberg, 2015 Hare K. Child Health Division, Menzies School of Health Research, Darwin, Australia aut Grimwood K. Menzies Health Institute Queensland, Griffith University, Gold Coast Health, Gold Coast, Australia aut Chang A. Child Health Division, Menzies School of Health Research, Darwin, Australia aut Chatfield M. Menzies School of Health Research, Darwin, Australia aut Valery P. Menzies School of Health Research, Darwin, Australia aut Leach A. Child Health Division, Menzies School of Health Research, Darwin, Australia aut Smith-Vaughan H. Child Health Division, Menzies School of Health Research, Darwin, Australia aut Morris P. Child Health Division, Menzies School of Health Research, Darwin, Australia aut Byrnes C. Department of Paediatrics, University of Auckland, Auckland, New Zealand aut Torzillo P. Sydney Medical School, University of Sydney, Sydney, Australia aut Cheng A. Infectious Disease Epidemiology Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/11(2015-11-01), 2275-2285 0934-9723 34:11<2275 2015 34 10096 https://doi.org/10.1007/s10096-015-2480-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-015-2480-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hare K. Child Health Division, Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Grimwood K. Menzies Health Institute Queensland, Griffith University, Gold Coast Health, Gold Coast, Australia aut NATIONALLICENCE 700 1- Chang A. Child Health Division, Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Chatfield M. Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Valery P. Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Leach A. Child Health Division, Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Smith-Vaughan H. Child Health Division, Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Morris P. Child Health Division, Menzies School of Health Research, Darwin, Australia aut NATIONALLICENCE 700 1- Byrnes C. Department of Paediatrics, University of Auckland, Auckland, New Zealand aut NATIONALLICENCE 700 1- Torzillo P. Sydney Medical School, University of Sydney, Sydney, Australia aut NATIONALLICENCE 700 1- Cheng A. Infectious Disease Epidemiology Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/11(2015-11-01), 2275-2285 0934-9723 34:11<2275 2015 34 10096