AbstractBronchiectasis unrelated to cystic fibrosis (CF) is prevalent in Australian Indigenous children. Early detection, knowledge of the bacteriology, and appropriate treatment are needed to prevent disease progression and early death in adulthood. This thesis presents the first research on the upper and lower airway bacteriology of non-CF bronchiectasis in Australian Indigenous children, and the impact of a macrolide antibiotic (azithromycin). Gaps in methodology were addressed. Principal findings were:
1. The predominant bacterial pathogens causing lower airway infection were nontypeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as in other paediatric populations with non-CF bronchiectasis.
2. Nasopharyngeal (NP) swabs were more sensitive than oropharyngeal swabs for detecting upper airway carriage of these three pathogens.
3. Strain concordance of bacteria isolated from NP and lower airway specimens from children with lower airway infection was very high. This strongly supports the hypothesis that aspiration of NP secretions contributes to the pathology of non-CF bronchiectasis.
4. There was a differential effect of recent azithromycin use on NP carriage (reduced) and lower airway infection (not reduced, with the probable exception of M. catarrhalis). Both NP carriage of and lower airway infection by macrolideresistant S. pneumoniae were significantly increased.
5. Long-term azithromycin use was associated with reduced NP carriage of the three main bacteria, but increased carriage of macrolide-resistant S. pneumoniae and Staphylococcus aureus, in a ‘cumulative dose-response’ relationship.
6. In a randomised controlled trial, similar long-term impacts on NP carriage were seen, and respiratory exacerbation frequency was significantly reduced, in the azithromycin compared to the placebo group. This demonstrated azithromycin’s effectiveness despite increased macrolide resistance.
These findings will inform management of children with non-CF bronchiectasis. Research on the impact of increased macrolide resistance in the community is recommended until a better understanding of azithromycin’s mode of action in reducing exacerbation frequency is reached.
Note: Please note that some articles in the thesis are available in hard copy only.
|Date of Award||2014|
|Supervisor||Heidi Smith-Vaughan (Supervisor)|