Longitudinal nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in indigenous Australian and Alaska native children with bronchiectasis

PLoS One. 2013 Aug 5;8(8):e70478. doi: 10.1371/journal.pone.0070478. Print 2013.

Abstract

Background: Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations.

Methods: Indigenous children aged 0.5-8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004-8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year.

Results: Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005-6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004-6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a 'cumulative dose-response' relationship.

Conclusions: Over time, similar (possibly age-related) changes in nasopharyngeal bacterial carriage were observed in Australian and Alaskan children with CSLD/bronchiectasis. However, there were also significant frequency-dependent differences in carriage and antibiotic resistance that coincided with azithromycin use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alaska
  • Australia
  • Bronchiectasis / drug therapy*
  • Bronchiectasis / microbiology*
  • Child
  • Child, Preschool
  • Drug Resistance, Bacterial
  • Drug Resistance, Microbial / physiology
  • Female
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / pathogenicity
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Moraxella catarrhalis / drug effects
  • Moraxella catarrhalis / pathogenicity
  • Nasopharynx / microbiology*
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / pathogenicity

Grants and funding

This work was supported by the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au/, National Health and Medical Research Council (NHMRC) project grants 389837 (clinical component) and 545223 (microbiology component), and Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islanders grant 1040830). The Alaskan study site received funding from the National Institutes of Health (http://www.nih.gov/) and the National Heart Lung and Blood Institute (http://www.nhlbi.nih.gov/, No.U26IHS3000001/01). KMH is supported by the NHMRC Gustav Nossal Postgraduate Scholarship 1038072 and the Australian Academy of Science's (http://science.org.au/) Douglas and Lola Douglas Scholarship; PCV is supported by an Australian Research Council (http://www.arc.gov.au/) Future Fellowship No.100100511; ACC and HSV are funded by NHMRC Career Development Fellowships 1009945 and 1024175; AJL is supported by the NHMRC Elizabeth Blackburn Research Fellowship 1020561; and ABC is supported by a NHMRC Practitioner Fellowship 545216. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.