Longitudinal Nasopharyngeal Carriage and Antibiotic Resistance of Respiratory Bacteria in Indigenous Australian and Alaska Native Children with Bronchiectasis

Abstract

BackgroundIndigenous 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.MethodsIndigenous 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.ConclusionsOver 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.

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

“…Importantly, patients receiving AZM were less likely to become colonized with respiratory pathogens but also were more likely to become colonized with macrolide-resistant microorganisms (32). In agreement with this notion, longitudinal studies of nasopharyngeal carriage of respiratory bacteria in indigenous Australian and Alaskan native children with bronchiectasis revealed that macrolide resistance was higher in Australian children, who received more AZM, than in Alaskan children (34).…”

“…Several clinical studies have examined their potential for AECOPD prevention (32)(33)(34)(35)(36)(37). In particular, long-term prophylaxis with AZM in patients with moderate to severe COPD has been associated with a significantly decreased number of exacerbations and an improved quality of life.…”

Prescribing azithromycin

“…2,3 Haemophilus influenzae is commonly susceptible to macrolides but resistance rates of 3-15% have been reported in Aboriginal and Torres Strait Islander children. 4 …”

Respiratory Exacerbations in Indigenous Children From Two Countries With Non-Cystic Fibrosis Chronic Suppurative Lung Disease/Bronchiectasis

“…Th e baseline clinical and socioeconomic features and upper airway microbiology of this group have been published previously. 13,14 Th e purpose of this report is to (1) characterize the pattern of AREs in this cohort of children over at least 3 years of observation and (2) identify clinical features that increased the risk of recurrent and severe AREs requiring hospitalization.…”