A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand.
BACKGROUND
Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis.


METHODS
In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 mu g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand.


RESULTS
Over a 27-month period, 60 patients were enrolled to receive either G-CSF (30 patients, 18 of whom had culture-confirmed melioidosis) or placebo (30 patients, 23 of whom had culture-confirmed melioidosis). Mortality rates were similar in both groups (G-CSF group, 70%; placebo group, 87%; risk ratio, 0.81; 95% confidence interval, 0.61-1.06; P=.2), including among patients with confirmed melioidosis (83% vs. 96%; P=.3). The duration of survival was longer for patients who received G-CSF than for patients who received placebo (33 h vs. 18.6 h; hazard ratio, 0.56; 95% confidence interval, 0.31-1.00; P=.05).


CONCLUSIONS
Receipt of G-CSF is associated with a longer duration of survival but is not associated with a mortality benefit in patients with severe sepsis who are suspected of having melioidosis in Thailand. We hypothesize that G-CSF may "buy time" for severely septic patients, but survival is more likely to be improved by management of associated metabolic abnormalities and organ dysfunction associated with severe sepsis.
Cheng
Allen C
AC
Menzies School of Health Research, Charles Darwin University, Darwin, Australia. allen.cheng@menzies.edu.au
Limmathurotsakul
Direk
D
Chierakul
Wirongrong
W
Getchalarat
Nongluk
N
Wuthiekanun
Vanaporn
V
Stephens
Dianne P
DP
Day
Nicholas P J
NP
White
Nicholas J
NJ
Chaowagul
Wipada
W
Currie
Bart J
BJ
Peacock
Sharon J
SJ
D018806:APACHE; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D000078224:Lenograstim; D008554:Melioidosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016019:Survival Analysis; D013785:Thailand; D016896:Treatment Outcome
D010919:Placebos; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim