Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Chest. 2021 Nov;160(5):1624-1633. doi: 10.1016/j.chest.2021.04.015. Epub 2021 Apr 17.
Pseudomonas aeruginosa (PA) is a common cause of respiratory infection and morbidity. Pseudomonas elastase is an important virulence factor regulated by the lasR gene. Whether PA elastase activity is associated with worse clinical outcomes in ICU patients is unknown.
Is there an association between PA elastase activity and worse host outcomes in a cohort of ICU patients?
PA respiratory isolates from 238 unique ICU patients from two tertiary-care centers within the University of Pittsburgh Medical Center health system were prospectively collected and screened for total protease and elastase activity, biofilm production, antimicrobial resistance, and polymicrobial status. The association between pathogen characteristics and 30-day and 90-day mortality was calculated using logistic regression. For subgroup analysis, two patterns of early (≤72 h) and late sample (>72 h) collection from the index ICU admission were distinguished using a finite mixture model. Lung inflammation and injury was evaluated in a mouse model using a PA high elastase vs low elastase producer.
PA elastase activity was common in ICU respiratory isolates representing 75% of samples and was associated with increased 30-day mortality (adjusted OR [95% CI]: 1.39 [1.05-1.83]). Subgroup analysis demonstrated that elastase activity was a risk factor for 30- and 90-day mortality in the early sample group, whereas antimicrobial resistance was a risk factor for 90-day mortality in the late sample group. Whole genome sequencing of high and low elastase producers showed that predicted loss-of-function lasR genotypes were less common among high elastase producers. Mice infected with a high elastase producer showed increased lung bacterial burden and inflammatory profile compared with mice infected with a low elastase producer.
Elastase activity is associated with 30-day ICU mortality. A high elastase producing clinical isolate confers increased lung tissue inflammation compared with a low elastase producer in vivo.
铜绿假单胞菌（PA）是引起呼吸道感染和发病的常见原因。弹性蛋白酶是一种受 lasR 基因调控的重要毒力因子。PA 弹性酶活性是否与 ICU 患者的临床结局恶化有关尚不清楚。
在匹兹堡大学医学中心医疗系统的两家三级保健中心的 238 名 ICU 患者队列中，PA 弹性酶活性与宿主结局恶化之间是否存在关联？
前瞻性收集并筛选来自匹兹堡大学医学中心医疗系统的两家三级保健中心的 238 名 ICU 患者的 238 株 PA 呼吸道分离株，以检测总蛋白酶和弹性酶活性、生物膜形成、抗菌药物耐药性和多微生物状态。使用逻辑回归计算病原体特征与 30 天和 90 天死亡率之间的关联。对于亚组分析，使用有限混合模型区分指数 ICU 入院时早期（≤72 h）和晚期（>72 h）采集的两个样本模式。使用 PA 高弹性酶与低弹性酶产生者在小鼠模型中评估肺炎症和损伤。
ICU 呼吸道分离株中常见 PA 弹性酶活性，占样本的 75%，与 30 天死亡率增加相关（调整后的比值比[95%CI]：1.39 [1.05-1.83]）。亚组分析表明，弹性酶活性是早期样本组 30 天和 90 天死亡率的危险因素，而晚期样本组的抗菌药物耐药性是 90 天死亡率的危险因素。高弹性酶和低弹性酶产生者的全基因组测序显示，预测 lasR 基因缺失功能的基因型在高弹性酶产生者中较少见。与感染低弹性酶产生者的小鼠相比，感染高弹性酶产生者的小鼠肺部细菌负荷和炎症特征增加。
弹性酶活性与 30 天 ICU 死亡率相关。与低弹性酶产生者相比，高弹性酶产生的临床分离株在体内引起的肺部组织炎症增加。
