Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
PLoS One. 2013 Aug 5;8(8):e70478. doi: 10.1371/journal.pone.0070478. Print 2013.
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.
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.
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.
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.
澳大利亚和阿拉斯加的土著儿童慢性化脓性肺病（CSLD）/支气管扩张症的发病率非常高。抗生素，包括澳大利亚的阿奇霉素（azithromycin）和两国的短期β-内酰胺疗法，经常被用于治疗这些患者。在支气管扩张症观察性研究中，我们在几年内检查了这两个接受过 PCV7 疫苗接种的人群中鼻咽部携带的呼吸道细菌及其抗生素耐药性。
2004 年至 2008 年，我们从澳大利亚偏远地区（n=79）和阿拉斯加（n=41）招募了患有 CSLD/支气管扩张症的 0.5-8.9 岁土著儿童，他们参加了一项前瞻性队列研究。在定期的研究访问中，记录了过去 2 周内的抗生素使用情况，并采集了鼻咽拭子进行培养和药敏试验。对呼吸道细菌携带和抗生素耐药性的分析是基于基线和最终的拭子，以及每年的总拭子。
肺炎链球菌的携带情况在一段时间内变化不大。相比之下，流感嗜血杆菌的携带减少，金黄色葡萄球菌的携带增加（阿拉斯加儿童的携带率从 2005 年至 2006 年的 0%增加到 2010 年的 23%）；这些变化与年龄增长有关。莫拉氏菌属（Moraxella catarrhalis）的携带情况在澳大利亚儿童中显著下降，但在阿拉斯加儿童中没有（从 2004 年至 2006 年的 64%下降到 2010 年的 11%）。虽然两组β-内酰胺类抗生素的使用情况相似，但澳大利亚儿童使用的阿奇霉素更多。与阿拉斯加儿童相比，澳大利亚儿童的大环内酯类抗生素耐药性显著更高，而流感嗜血杆菌的β-内酰胺类耐药性在阿拉斯加儿童中更高。阿奇霉素的使用与肺炎链球菌、流感嗜血杆菌和莫拉氏菌属的携带量减少显著相关，但与金黄色葡萄球菌和耐大环内酯类的肺炎链球菌和金黄色葡萄球菌携带量增加相关（携带者的比例和所有拭子），呈“累积剂量反应”关系。
随着时间的推移，在患有 CSLD/支气管扩张症的澳大利亚和阿拉斯加儿童中，鼻咽部细菌携带情况出现了类似的（可能与年龄相关的）变化。然而，在携带和抗生素耐药性方面也存在显著的、与频率相关的差异，这些差异与阿奇霉素的使用有关。
