Quantitative and Qualitative Assessments of Cholesterol Association With Bacterial Infection Type in Sepsis and Septic Shock

Background: Reduced cholesterol levels are associated with increased organ failure and mortality in sepsis. Cholesterol levels may vary by infection type (gram negative vs positive), possibly reflecting differences in cholesterol-mediated bacterial clearance. Methods: This was a secondary analysis of a combined data set of 2 prospective cohort studies of adult patients meeting Sepsis-3 criteria. Infection types were classified as gram negative, gram positive, or culture negative. We investigated quantitative (levels) and qualitative (dysfunctional high-density lipoprotein [HDL]) cholesterol differences. We used multivariable logistic regression to control for disease severity. Results: Among 171 patients with sepsis, infections were gram negative in 67, gram positive in 46, and culture negative in 47. Both gram-negative and gram-positive infections occurred in 11 patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels were lower for culture-positive sepsis at enrollment (TC, P <.001; LDL-C, P <.001; HDL-C, P =.011) and persisted after controlling for disease severity. Similarly, cholesterol levels were lower among culture-positive patients at 48 hours (TC, P =.012; LDL-C, P =.029; HDL-C, P =.002). Triglyceride (TG) levels were lower at enrollment (P =.033) but not at 48 hours (P =.212). There were no differences in dysfunctional HDL. Among bacteremic patients, cholesterol levels were lower at enrollment (TC, P =.010; LDL-C, P =.010; HDL-C, P ≤.001; TG, P =.005) and at 48 hours (LDL-C, P =.027; HDL-C, P <.001; TG, P =.020), except for 48 hour TC (P =.051). In the bacteremia subgroup, enrollment TC and LDL-C were lower for gram-negative versus gram-positive infections (TC, P =.039; LDL-C, P =.023). Conclusion: Cholesterol levels are significantly lower among patients with culture-positive sepsis and bacteremia.