Mayer-Hamblett Nicole, Rosenfeld Margaret, Gibson Ronald L, Ramsey Bonnie W, Kulasekara Hemantha D, Retsch-Bogart George Z, Morgan Wayne, Wolter Daniel J, Pope Christopher E, Houston Laura S, Kulasekara Bridget R, Khan Umer, Burns Jane L, Miller Samuel I, Hoffman Lucas R
1 Department of Pediatrics.
Am J Respir Crit Care Med. 2014 Aug 1;190(3):289-97. doi: 10.1164/rccm.201404-0681OC.
Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease.
To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes.
A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism.
P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31% of new-onset cultures, 48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%, and 65%, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95% confidence interval, 1.11-1.84).
In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease.
铜绿假单胞菌在囊性纤维化（CF）肺部感染期间会发生表型变化。尽管黏液样变传统上与向慢性感染的转变相关，但我们推测其他体外表型也与这种转变相关并导致疾病。
描述铜绿假单胞菌体外表型、感染阶段和临床结果之间的关系。
对总共649例新确诊铜绿假单胞菌感染的CF儿童进行了中位时间为5.4年的随访，在此期间共收集了2594株铜绿假单胞菌分离株。对分离株评估了26种体外细菌表型，包括运动性、外产物产生、菌落形态、生长和代谢的指标。
培养时的铜绿假单胞菌表型与感染阶段（新发、间歇性或慢性）以及主要临床结果，即随后2年内肺部加重（PE）的发生均相关。两种铜绿假单胞菌体外表型最能区分感染阶段：绿脓菌素产生（新发培养物中占31%，间歇性培养物中占48%，慢性培养物中占69%）和蛋白酶产生减少（分别为31%、39%和65%）。预测随后发生PE的最佳铜绿假单胞菌表型指标是黏液样变（比值比，1.75；95%置信区间，1.19 - 2.57）和颤动运动减少（比值比，1.43；95%置信区间，1.11 - 1.84）。
在这项关于CF铜绿假单胞菌适应性的大型流行病学研究中，铜绿假单胞菌分离株表现出两种最能区分早期和晚期感染阶段的体外表型。在测试的众多表型中，黏液样变和颤动运动减少最能预测随后的PE。这些表型表明可能是向慢性感染转变和肺部疾病进展的有用预后标志物。
