Filgrastim in patients with pneumonia and severe sepsis or septic shock.
OBJECTIVE
Evaluate the safety of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) administration, combined with standard therapy, in patients with pneumonia and either septic shock or severe sepsis who were receiving mechanical ventilation.


METHODS
Multicenter, double-blind, randomized, placebo-controlled study.


METHODS
ICU, multicenter.


METHODS
Eighteen patients with pneumonia and hypotension, or in the absence of shock, two or more end-organ dysfunctions, were enrolled and treated. Baseline acute physiology and chronic health evaluation II scores and median age for the filgrastim (n = 12) and placebo (n = 6) groups were 25.0 and 49.5 years and 31.5 and 56.5 years, respectively.


METHODS
Filgrastim (300 microg) or placebo was administered IV daily for up to 5 days.


RESULTS
Study end points included safety; biological response, including endogenous cytokine levels, endotoxin levels, and neutrophil counts; and mortality. Cytokine and endotoxin levels were highly variable in both groups. By day 29, 3 of 12 filgrastim-treated patients and 4 of 6 placebo-treated patients had died. There were no differences in types and occurrences of adverse events, including ARDS, or in outcome between the two groups. Three of four placebo-treated patients had persistent bacterial growth on bronchoscopy repeated after 48 h compared with 2 of 10 filgrastim-treated patients.


CONCLUSIONS
Filgrastim appeared to be well tolerated in this population of patients with pneumonia and severe sepsis or septic shock. Larger studies to determine the benefit of filgrastim in patients with pneumonia and sepsis or organ dysfunction are warranted.
Wunderink
R
R
University of Tennessee, College of Medicine, Memphis, TN, USA. wunderir@methodisthealth.org
Leeper
K
K
Schein
R
R
Nelson
S
S
DeBoisblanc
B
B
Fotheringham
N
N
Logan
E
E
D000328:Adult; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000517:prevention & control; D011014:Pneumonia / Q000188:drug therapy*; D011994:Recombinant Proteins; D012128:Respiratory Distress Syndrome / Q000517:prevention & control; D018805:Sepsis / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim