Hare KM

Grimwood K

Chang AB

Chatfield MD

Valery PC

Leach AJ

Smith-Vaughan HC

Morris PS

Byrnes CA

Torzillo PJ

Cheng AC

2015-11

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.

Child Health Division, Menzies School of Health Research, Darwin, Australia. Kim.Hare@menzies.edu.au..

Menzies Health Institute Queensland, Griffith University, Gold Coast Health, Gold Coast, Australia..

Child Health Division, Menzies School of Health Research, Darwin, Australia.. Department of Respiratory and Sleep Medicine, Queensland Children's Medical Research Institute, Children's Health, Queensland University of Technology, Brisbane, Australia..

Menzies School of Health Research, Darwin, Australia..

Menzies School of Health Research, Darwin, Australia.. Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia..

Child Health Division, Menzies School of Health Research, Darwin, Australia..

Child Health Division, Menzies School of Health Research, Darwin, Australia.. School of Medicine, Griffith University, Gold Coast, Australia..

Child Health Division, Menzies School of Health Research, Darwin, Australia.. Department of Paediatrics, Royal Darwin Hospital, Darwin, Australia..

Department of Paediatrics, University of Auckland, Auckland, New Zealand.. Paediatric Respiratory Medicine, Starship Children's Health, Auckland, New Zealand..

Sydney Medical School, University of Sydney, Sydney, Australia.. Royal Prince Alfred Hospital, Sydney, Australia..

Infectious Disease Epidemiology Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.. Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Australia..

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2015-11; 34(11): 2275-85

https://pubmed.ncbi.nlm.nih.gov/26363637/?otool=iaurydwlib

https://hdl.handle.net/10137/5439

Anti-Bacterial Agents

Australia

Azithromycin

Bacteria

Bacterial Infections

Bronchiectasis

Carrier State

Child

Child, Preschool

Female

Humans

Infant

Macrolides

Male

Nasopharynx

New Zealand

Pacific Islands

Placebos

Population Groups

Drug Resistance, Bacterial

Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

Journal Article

Multicenter Study

Randomized Controlled Trial

Publication