Department of Paediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Adult Cystic Fibrosis Centre, The Prince Charles Hospital and QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Curr Opin Pulm Med. 2019 Nov;25(6):636-645. doi: 10.1097/MCP.0000000000000616.
This review provides an update on definitions of chronicity of infection, approaches to airway sampling to detect infection, strategies for Pseudomonas aeruginosa eradication, impact of cystic fibrosis transmembrane regulator protein (CFTR) modulators and future challenges for clinical trials.
Rates of P. aeruginosa have decreased over the past two decades with establishment of effective eradication protocols. Definitions of chronic P. aeruginosa infection have required adaptation for healthier populations. Although molecular (PCR) approaches to early P. aeruginosa detection are sensitive, to date, earlier diagnosis has not impacted on clinical outcomes. Despite eradication regimens, some people with early P. aeruginosa fail to clear their infection. Most people also experience a recurrence and eventual transition to chronic infection. Several recent studies sought to address this gap. CFTR modulators (predominantly ivacaftor) demonstrated reduced P. aeruginosa density, although infection may persist or recur demonstrating the need for continued antiinfective therapies in the modulator era.
Future studies of approaches to P. aeruginosa eradication will be complex due to expanded availability and ongoing competitive clinical trials of CFTR modulators. Studies to address optimal eradication therapy, particularly in adults, will be required, though adequate recruitment to power these studies may prove challenging.
目的综述:本文综述了慢性感染的定义、气道采样检测感染的方法、铜绿假单胞菌根除策略、囊性纤维化跨膜转导调节蛋白(CFTR)调节剂的影响以及临床试验的未来挑战。
最近发现:在建立有效的根除方案后,过去二十年来铜绿假单胞菌的发生率有所下降。慢性铜绿假单胞菌感染的定义需要适应于更健康的人群。虽然分子(PCR)方法对早期铜绿假单胞菌的检测具有敏感性,但迄今为止,早期诊断并未影响临床结果。尽管采用了根除方案,一些早期感染铜绿假单胞菌的患者仍未能清除感染。大多数人也会出现复发,最终发展为慢性感染。最近的几项研究试图解决这一差距。CFTR 调节剂(主要是 ivacaftor)显示出降低铜绿假单胞菌密度的效果,尽管感染可能持续存在或复发,这表明在调节剂时代仍需要持续使用抗感染治疗。
总结:由于 CFTR 调节剂的广泛应用和正在进行的竞争临床试验,未来铜绿假单胞菌根除方法的研究将变得复杂。需要研究最佳的根除治疗方法,特别是在成人中,但可能难以招募足够的患者来进行这些研究。