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 sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank chi(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 <or= 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank chi(2) 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.
Moore
Christopher C
CC
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ccm5u@virginia.edu
Jacob
Shevin T
ST
Pinkerton
Relana
R
Banura
Patrick
P
Meya
David B
DB
Reynolds
Steven J
SJ
Kenya-Mugisha
Nathan
N
Mayanja-Kizza
Harriet
H
Scheld
W Michael
WM
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000078102:Lumefantrine; D008288:Malaria / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality*; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
D000890:Anti-Infective Agents; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D000077549:Artemether; D000078102:Lumefantrine