Serum Endotoxin as a Diagnostic Biomarker for Legionella pneumophila in Gram-Negative Infections

Rapid and accurate differentiation of Legionella pneumophila infections from other gram-negative bacterial infections remains a significant challenge in intensive care medicine. Despite its relatively low in vitro endotoxic activity, clinical observations have suggested elevated circulating endotoxin levels in patients with legionellosis. This retrospective cohort study analyzed 118 critically ill patients with microbiologically confirmed infections admitted to an intensive care unit between January 2020 and December 2023. Patients were classified into four pathogen groups: Legionella pneumophila (n = 18), other gram-negative bacteria (n = 68), gram-positive bacteria (n = 24), and fungi (n = 8). Serum endotoxin levels were measured within 24 h of ICU admission using a kinetic chromogenic Limulus amebocyte lysate assay. Patients with Legionella pneumophila infection demonstrated significantly higher endotoxin levels than those with other gram-negative infections (mean 2.15 ± 1.28 vs 0.61 ± 0.74 EU/mL). Using a threshold of > 2.5 EU/mL, endotoxin quantification showed a sensitivity of 77.8% and specificity of 89.7% for differentiating Legionella infections, with a negative predictive value of 95.3%. Multivariable logistic regression indicated that endotoxin > 2.5 EU/mL remained independently associated with Legionella infection (adjusted OR 15.7, 95% CI 3.84-64.2, p < 0.001). These findings suggest that serum endotoxin quantification may serve as a useful adjunctive biomarker to aid early identification of Legionella pneumophila infection in critically ill patients.