Filgrastim in patients with pneumonia and severe sepsis or septic shock

Study objectives: 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 sev ere sepsis who were receiving mechanical ventilation. Design: Multicenter, double-blind, randomized, placebo-controlled study. Setting: ICU, multicenter. Patients: Eighteen patients with pneumonia and hypotension, or in the absen ce of shock, two or more end-organ dysfunctions, were enrolled and treated. Baseline acute physiology and chronic health evaluation II scores and medi an 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. Intervention: Filgrastim (300 mug) or placebo was administered nr daily for up to 5 days. Measurements and results: Study end points included safety; biological resp onse, including endogenous cytokine levels, endotoxin levels, and neutrophi l counts; and mortality. Cytokine and endotoxin levels were highly variable in both groups. By day 29, 3 of I2 filgrastim-treated patients and 4 of 6 placebo-treated patients had died. There were no differences in types and o ccurrences of adverse events, including ARDS, or in outcome between the two groups. Three of four placebo-treated patients had persistent bacterial gr owth on bronchoscopy repeated after 48 h compared with 2 of 10 filgrastim-t reated patients. Conclusion: Filgrastim appeared to be well tolerated in this population of patients with pneumonia and severe sepsis or septic shock. Larger studies t o determine the benefit of filgrastim in patients with pneumonia and sepsis or organ dysfunction are warranted.