Treatment of Severe Sepsis with Artemether-Lumefantrine Is Associated with Decreased Mortality in Ugandan Patients without Malaria

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sep- sis. Because artemisininsimprove survival in murine sepsis models, we performed a post hoc analysisof the association between the use of artemether- lumefantrine(A-L) and mortality in patients with or without malaria. In patients with neg- ative malaria smears ( N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortal- ity among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank χ 2 = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores ≤ 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank χ 2 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.