title: Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection.
abstract: BACKGROUND
  Diabetic foot infections cause substantial morbidity and mortality. Neutrophil superoxide generation, a crucial part of neutrophil bactericidal activity, is impaired in diabetes. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil function. We assessed G-CSF as adjuvant therapy for the treatment of severe foot infections in diabetic patients.
  
  
  METHODS
  40 diabetic patients with foot infections were enrolled in a double-blind placebo-controlled study. On admission, patients were randomly assigned G-CSF (filgrastim) therapy (n = 20) or placebo (n = 20) for 7 days. Both groups received similar antibiotic and insulin treatment. Neutrophils from the peripheral blood of these participants and from healthy controls were stimulated with opsonised zymosan, and superoxide production was measured by a spectrophotometric assay (reduction of ferricytochrome C).
  
  
  RESULTS
  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), shorter hospital stay (10 [7-31] vs 17.5 [9-100] days; p = 0.02), and a shorter 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 two placebo recipients underwent to amputation and two had extensive debridement under anaesthesia. After 7 days' treatment, neutrophil superoxide production was significantly higher in the G-CSF group than in the placebo group (16.1 [4.2-24.2] vs 7.3 [2.1-11.5] nmol per 10(6) neutrophils in 30 min; p < 0.0001). G-CSF therapy was generally well tolerated.
  
  
  CONCLUSIONS
  G-CSF treatment was associated with improved clinical outcome of foot infection in diabetic patients. This improvement may be related to an increase in neutrophil superoxide production.
authors.affiliation: King's Diabetes Centre, King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gough
authors.forename: M
authors.initials: M
authors.lastname: Clapperton
authors.forename: N
authors.initials: N
authors.lastname: Rolando
authors.forename: A V
authors.initials: AV
authors.lastname: Foster
authors.forename: J
authors.initials: J
authors.lastname: Philpott-Howard
authors.forename: M E
authors.initials: ME
authors.lastname: Edmonds
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents; D001424:Bacterial Infections / Q000150:complications / Q000628:therapy*; D002481:Cellulitis / Q000150:complications / Q000628:therapy*; D017719:Diabetic Foot / Q000150:complications* / Q000382:microbiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim