Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream.
BACKGROUND
Topical antimicrobial therapy of infected diabetic foot ulcers can focus on the wound and avoid the adverse effects of systemic anti-infective agents. We compared the efficacy of outpatient treatment using an investigational topical antimicrobial peptide, pexiganan acetate cream, with the efficacy of systemic therapy using an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers.


METHODS
In 2 consecutive, double-blind, controlled trials (study 303 and study 304), we randomized diabetic patients with a mildly infected diabetic foot ulcer to receive the active topical agent or active oral antibiotic, plus a respective inactive placebo. The primary outcome of interest was clinical cure or improvement of the infection. Secondary outcomes included eradication of wound pathogens and wound healing, which was documented by a semiquantitative scoring system.


RESULTS
Overall, 835 patients were randomized; those in each treatment arm were similar with regard to demographic and clinical characteristics. Although study 303 failed to demonstrate equivalence, study 304 and the combined data for the 2 trials demonstrated equivalent results (within the 95% confidence interval) for topical pexiganan and oral ofloxacin in clinical improvement rates (85%-90%), overall microbiological eradication rates (42%-47%), and wound healing rates. The incidence of worsening cellulitis (2%-4%) and amputation (2%-3%) did not differ significantly between treatment arms. Bacterial resistance to ofloxacin emerged in some patients who received ofloxacin, but no significant resistance to pexiganan emerged among patients who received pexiganan.


CONCLUSIONS
Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.
Lipsky
Benjamin A
BA
Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98116-1597, USA. Benjamin.Lipsky@med.va.gov
Holroyd
Kenneth J
KJ
Zasloff
Michael
M
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy*; D017719:Diabetic Foot / Q000150:complications*; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D009824:Ointments / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D009824:Ointments; D010919:Placebos; D015242:Ofloxacin; C093828:pexiganan