Institute of International Health, Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Copenhagen, Denmark.
Institute of International Health, Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Adv Drug Deliv Rev. 2015 May;85:7-23. doi: 10.1016/j.addr.2014.11.017. Epub 2014 Dec 2.
Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms of biofilm formation and antimicrobial tolerance and resistance are reviewed. Potential anti-biofilm therapeutic targets such as weakening of biofilms by quorum-sensing inhibitors or antibiotic killing guided by pharmacokinetics and pharmacodynamics of antibiotics are presented. The vicious circle of adaptive evolution of the persisting bacteria imposes important therapeutic challenges and requires development of new drug delivery systems able to reach the different niches occupied by the bacteria in the lung of cystic fibrosis patients.
肺部感染是囊性纤维化患者发病率和死亡率的主要原因,主要由铜绿假单胞菌引起。其生物膜生长模式使得感染无法根除,并导致气道慢性炎症。本文综述了生物膜形成的一般机制以及抗菌药物耐受性和耐药性的产生机制。并提出了一些潜在的抗生物膜治疗靶点,例如通过群体感应抑制剂削弱生物膜,或者根据抗生素药代动力学和药效学指导抗生素杀菌。持续存在的细菌适应性进化的恶性循环带来了重要的治疗挑战,这需要开发新的药物输送系统,使其能够到达囊性纤维化患者肺部中细菌占据的不同小生境。