Phenylalanine- and leucine-defined metabolic types identify high mortality risk in patients with severe infection

Objective: To investigate the prognostic value of phenylalanine and leucine in patients with severe infection. Methods: Ninety-three patients with infection who had a quick Sequential Organ Failure Assessment (qSOFA) score ≥2 were enrolled. Plasma phenylalanine, leucine, albumin, C-reactive protein, pre-albumin, and transferrin were measured and the SOFA score at enrollment was calculated after hospitalization. Results: During the 3-month follow-up, 30 (32.3%) patients died. Death was associated with higher SOFA scores, a higher incidence of bacteremia and admission to the intensive care unit, higher C-reactive protein and phenylalanine levels, worse kidney function, and lower pre-albumin and transferrin levels. Patients were categorized into three groups: high-risk type 1 (phenylalanine ≥84 μM), high-risk type 2 (phenylalanine <84 μM and leucine <93 μM), and low-risk (other). Compared to the low-risk type patients, high-risk type 1 and 2 patients had higher mortality rates (hazard ratio 10.1 (95% CI 2.33–43.5) and hazard ratio 5.56 (95% CI 1.22–25.4), respectively). Type 1 patients had higher SOFA scores, a higher incidence of admission to the intensive care unit, and higher C-reactive protein and leucine levels. Type 2 patients had lower albumin and hemoglobin levels. Multivariable analysis showed that both high-risk types were independent predictors of death. Conclusions: Phenylalanine- and leucine-defined risk classifications provide metabolic information with prognostic value for patients with severe infection.