RANDOMIZED PLACEBO-CONTROLLED TRIAL OF GRANULOCYTE-COLONY-STIMULATINGFACTOR IN DIABETIC FOOT INFECTION

Background Diabetic foot infections cause substantial morbidity and mo rtality. Neutrophil superoxide generation, a crucial part of neutrophi l bactericidal activity, is impaired in diabetes. Granulocyte-colony s timulating factor (G-CSF) increases the release of neutrophils from th e bone marrow and improves neutrophil function. We assessed G-CSF as a djuvant therapy for the treatment of severe foot infections in diabeti c patients. Methods 40 diabetic patients with foot infections were enr olled in a double-blind placebo-controlled study. On admission, patien ts were randomly assigned G-CSF (filgrastim) therapy (n=20) or placebo (n=20) for 7 days. Both groups received similar antibiotic and insuli n treatment. Neutrophils from the peripheral blood of these participan ts and from healthy controls were stimulated with opsonised zymosan, a nd superoxide production was measured by a spectrophotometric assay (r eduction of ferricytochrome C). Findings G-CSF therapy was associated with earlier eradication of pathogens from the infected ulcer (median 4 [range 2-10] vs 8 [2-79] days in the placebo group; p=0.02), quicker resolution of cellulitis (7 [5-20] vs 12 [5-93] days; p=0.03), shorte r hospital stay (10 [7-31] vs 17.5 [9-100] days; p=0.02), and a shorte r duration of intravenous antibiotic treatment (8.5 [5-30] vs 14.5 [8- 63] days; p=0.02). No G-CSF-treated patient needed surgery, whereas tw o placebo recipients underwent toe amputation and two had extensive de bridement under anaesthesia. After 7 days' treatment, neutrophil super oxide production was significantly higher in the G-CSF group than in t he placebo group (16.1 [42-24.2] vs 7.3 [2.1-11.5] nmol per 10(6) neut rophils in 30 min; p<0.0001). G-CSF therapy was generally well tolerat ed. Interpretation G-CSF treatment was associated with improved clinic al outcome of foot infection in diabetic patients. This improvement ma y be related to an increase in neutrophil superoxide production.