Pseudomonas Elastase Activity Linked to Increased Risk of 30-Day ICU Mortality

In patients with respiratory Pseudomonas aeruginosa infection, an increase in the bacterial production of elastase may increase lung tissue inflammation, and is associated with an increase in 30-day intensive care unit (ICU) mortality, according to the results of a study published in CHEST.

P aeruginosa, a Gram-negative opportunistic bacterium, is a significant cause of acute lower respiratory tract infections among patients in ICU. Such infections have been associated with increased length of stay in ICU and lengthened need for mechanical ventilation.

The lasR gene regulates the pseudomonas elastase enzyme (also known as T2SS exoprotease). In previous mouse models, it has been observed that the bacterial elastase leads to increased neutrophilic inflammation and lung tissue damage during acute intrapulmonary infection.

In the present study, investigators conducted an analysis of P aeruginosa respiratory isolates to determine whether P aeruginosa elastase activity negatively affects outcomes in ICU patients. To evaluate lung inflammation and injury, mouse models compared outcomes of high vs low pseudomonas elastase production.

The investigators collected P aeruginosa respiratory isolates from 238 patients at 2 tertiary care centers of the University of Pittsburgh Medical Center health system and used logistic regression to calculate the association between pathogenic characteristics and mortality rates at 30 and 90days.

P aeruginosa elastase and protease activity was detectible in 75% and 71% of isolates, respectively, and high elastase and protease activity was detected in 44% and 32% of isolates, respectively. In addition, both elastase (odds ratio [OR], 1.34) and protease (OR, 1.34) were significantly linked to an increase in 30-day ICU mortality.

The investigators also conducted a subanalysis in which early (<72 hours) and late (>72 hours) samples were collected. In an adjusted model using early samples, elastase alone was linked to 90-day ICU morality (OR, 1.55). For late samples, results of elastase and protease activity were not significantly associated with ICU mortality at either 30 or 90 days; however, antimicrobial resistance was a risk factor for 90-day mortality.

Following whole genome sequencing of producers of high and low levels of elastase, the researchers confirmed that genotypic loss of lasR function was less common among high elastase producers. Compared with mice that were infected with low elastase producers, those that were infected with high elastase producers had an increased bacterial burden in the lungs and greater inflammatory profile.

“Further work is needed to determine mechanisms of lung injury caused by high elastase activity as it may serve as a target for point of care biomarkers and novel adjuvant therapies,” the authors concluded. 

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Zupetic J, Peñaloza HF, Bain W, et al. Elastase activity from Pseudomonas aeruginosa respiratory isolates and ICU mortality. CHEST. Published online April 17, 2021. doi:10.1016/j.chest.2021.04.015