Brand Name: Locilex 1% Topical Cream
Active Ingredient: pexiganan acetate
Indication: Topical antibiotic therapy of infected diabetic ulcers
Dosage Form(s): Topical Cream
Company Name: SmithKline Beecham Pharmaceuticals and Magainin Pharmaceuticals Inc.
Among the most common and severe complications of diabetes mellitus is the development of topical skin ulcers. These often occur at pressure points and at the extremities, and infected diabetic foot ulcers often result in limb loss. Poor peripheral blood circulation limits the body’s natural defenses against infection and slows the overall healing process. Aggressive wound care, including rigorous debridement and antibiotic therapy, are the cornerstones of management. Increasingly, however, these ulcers are colonized with pathogens that are resistant to traditional antibiotics. Furthermore, poor regional circulation often compromises attaining minimum inhibitory concentrations of antibiotics at the infected site. Consequently, topical application of an antibiotic could provide the therapeutic levels required to control local infection.
Locilex (pexiganan acetate) is a novel antibiotic designed for topical administration that appears to demonstrate activity against common pathogens associated with infected diabetic ulcers.
How It Works
Pexiganan is a synthetic 22-amino acid peptide with a broad spectrum of antimicrobial activity. It is a synthetic analog of magainin-2, which is a 23-amino acid peptide that was isolated from the skin of the African clawed frog. Pexiganan’s mechanism is similar to that of other magainins; it is thought to exert its bactericidal effect on susceptible organisms by altering the permeability of the cell membrane. Bacterial cell membranes are composed of negatively charged phospholipids that attract and bind the positively charged helices of the magainin peptides. These peptides do not seem to interact with bacterial receptors or enzymes.
Locilex: Clinical Study Results
Pexiganan acetate (Locilex) has been found to have a broad spectrum of antimicrobial activity against many gram-positive and gram-negative aerobic and anaerobic bacteria and certain species of fungi.
In vitro, 91% of aerobic strains of bacteria were susceptible to pexiganan, similar to the 91% for ofloxacin and 92% for ciprofloxacin. Only enterococci required the highest concentrations of pexiganan for eradication. Of the anerobes tested, 97% were susceptible to pexiganan. Thirty percent of candida isolates were inhibited by the drug.
In vivo studies have shown a 5-log reduction in the numbers of Pseudomonas aeruginosa in swine skin wounds and a 4-log reduction in perineal skin flora on human skin following topical application. Several large-scale clinical studies have been completed evaluating the drug in the treatment of infected diabetic foot ulcers. These were designed to compare the efficacy of pexiganan to that of the fluoroquinolone ofloxacin, which is recognized as being a standard of antibiotic therapy for infected diabetic ulcers.
In one study of 490 diabetics treated for 14-28 days, clinical response rates (improvement or resolution) were similar for pexiganan and ofloxacin, ranging from 84-93%; the frequencies of osteomyelitis and amputations were similar between groups. The cream was somewhat better tolerated than oral ofloxacin. In another study of 835 patients, the overall pathogen eradication rates were 66% for pexiganan compared to 82% for ofloxacin. However, clinical cures occurred in many pexiganan-treated patients who did not have microbial eradication, indicating that microbial eradication does not appear to be needed for a positive clinical response.
What The Patient Should Know
The use of a topical antibiotic may be more convenient than an oral dosage form for some patients, especially the elderly who have difficulty swallowing. While guidelines for the dosing and administration of pexiganan have not yet been formalized, it is certain that good wound debridement will be important in the effective use of this drug.