Ultrasensitive digital quantification of cytokines and bacteria predicts septic shock outcomes

细胞因子和细菌的超灵敏数字定量可预测脓毒症休克的结果

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作者:M Fatih Abasıyanık #, Krysta Wolfe #, Hoang Van Phan, Jing Lin, Bharathi Laxman, Steven R White, Philip A Verhoef, Gökhan M Mutlu, Bhakti Patel, Savaş Tay

Abstract

Quantification of pathogen and host biomarkers is essential for the diagnosis, monitoring, and treatment of infectious diseases. Here, we demonstrate sensitive and rapid quantification of bacterial load and cytokines from human biological samples to generate actionable hypotheses. Our digital assay measures IL-6 and TNF-α proteins, gram-negative (GN) and gram-positive (GP) bacterial DNA, and the antibiotic-resistance gene blaTEM with femtomolar sensitivity. We use our method to characterize bronchoalveolar lavage fluid from patients with asthma, and find elevated GN bacteria and IL-6 levels compared to healthy subjects. We then analyze plasma from patients with septic shock and find that increasing levels of IL-6 and blaTEM are associated with mortality, while decreasing IL-6 levels are associated with recovery. Surprisingly, lower GN bacteria levels are associated with higher probability of death. Applying decision-tree analysis to our measurements, we are able to predict mortality and rate of recovery from septic shock with over 90% accuracy.

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