Martínez-Solano Laura, Macia María D, Fajardo Alicia, Oliver Antonio, Martinez Jose L
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (Consejo Superior de Investigaciones Cientificas), Cantoblanco, Madrid, Spain.
Clin Infect Dis. 2008 Dec 15;47(12):1526-33. doi: 10.1086/593186.
Pseudomonas aeruginosa infections are increasingly associated with acute exacerbations in chronic obstructive pulmonary disease (COPD). We aimed to determine whether an underlying chronic infection might be behind this process and to determine the epidemiological characteristics of the isolates involved, to implement useful protocols for preventing and treating these infections.
P. aeruginosa isolates obtained from respiratory samples of 13 patients with COPD and from blood samples of 10 patients in intensive care units were investigated. In 8 patients with COPD, isolates were obtained during sequential exacerbation episodes. Five patients presented a single infection episode. Production of virulence determinants and genetic relationships were analyzed in all isolates.
Patients with COPD were usually infected with 1 P. aeruginosa clone that remained in the lung for years, without evidence of interpatient transmission. During chronic infection, each clone diversified, which led to the coexistence of isolates with different morphotypes and antibiotic susceptibility. Overall, P. aeruginosa evolved toward an increased mutation rate, increased antibiotic resistance, and reduced production of proteases. Isolates from samples of infected lungs tend to be less cytotoxic and motile and to produce more biofilm, compared with isolates from blood samples.
These results provide the first evidence supporting the hypothesis that P. aeruginosa causes chronic infections in COPD, with patterns of infection and evolution that resemble those observed in cystic fibrosis. Experience gained from treating cystic fibrosis might be useful for implementing new procedures for the prevention, diagnosis, and treatment of infection due to P. aeruginosa in COPD.
铜绿假单胞菌感染与慢性阻塞性肺疾病(COPD)的急性加重越来越相关。我们旨在确定这一过程背后是否可能存在潜在的慢性感染,并确定所涉及分离株的流行病学特征,以实施预防和治疗这些感染的有效方案。
对从13例COPD患者的呼吸道样本以及10例重症监护病房患者的血液样本中获得的铜绿假单胞菌分离株进行研究。在8例COPD患者中,在连续的加重发作期间获得分离株。5例患者出现单一感染发作。对所有分离株分析毒力决定因素的产生和遗传关系。
COPD患者通常感染单一的铜绿假单胞菌克隆,该克隆在肺中存留数年,无患者间传播的证据。在慢性感染期间,每个克隆发生分化,导致具有不同形态型和抗生素敏感性的分离株共存。总体而言,铜绿假单胞菌朝着突变率增加、抗生素耐药性增加和蛋白酶产生减少的方向进化。与血液样本中的分离株相比,感染肺样本中的分离株细胞毒性和运动性较低,生物膜产生更多。
这些结果提供了首个证据支持铜绿假单胞菌在COPD中引起慢性感染这一假说,其感染和进化模式类似于囊性纤维化中观察到的情况。从治疗囊性纤维化中获得的经验可能有助于实施针对COPD中铜绿假单胞菌感染的预防、诊断和治疗的新程序。