Pexiganan

Summary

Pexiganan (also called MSI‑78 or pexiganan acetate) is a synthetic 22‑amino‑acid antimicrobial peptide designed as an analogue of the frog‑derived magainin 2. It is being investigated as a topical cream for the treatment of mildly infected diabetic foot ulcers, where it aims to eradicate bacterial pathogens and promote wound healing.

Mechanism of Action

Pexiganan is a cationic amphipathic peptide that binds to bacterial membranes and adopts an antiparallel dimeric α‑helical structure upon contact. Biophysical studies show it inserts into the lipid bilayer, forming toroidal‑type pores that disrupt membrane integrity and increase permeability, leading to rapid bacterial cell death. Its mode of action is non‑receptor‑specific and therefore less prone to conventional resistance mechanisms.

What the Research Shows

Two phase‑III, double‑blind, multicentre trials in patients with infected diabetic foot ulcers compared 1 % pexiganan cream with oral ofloxacin. Combined data showed equivalent clinical cure or improvement rates of 85‑90 % and microbiological eradication of 42‑47 % for pexiganan, similar to the systemic comparator. No emergent resistance to pexiganan was observed, whereas some ofloxacin‑treated patients developed resistance. Earlier data reported ~90 % clinical success and 66 % pathogen eradication. Systematic reviews note that pexiganan may be as effective as oral antibiotics, but overall evidence is limited and of low certainty.

Reported Benefits

Clinical trials suggest that topical pexiganan can achieve cure or improvement rates comparable to oral fluoroquinolones for mildly infected diabetic foot ulcers, while avoiding systemic drug exposure. Its membrane‑disrupting action appears to limit the development of bacterial resistance, offering a potential advantage over conventional antibiotics.

Limitations of the Evidence

Evidence is confined to diabetic foot ulcer studies; other infection types have not been evaluated. Trial populations were moderate in size, and systematic reviews label the overall evidence as low‑certainty, citing small, heterogeneous studies and limited long‑term outcome data. Pexiganan has not achieved regulatory approval, and its safety profile beyond short‑term use remains incompletely characterized.

Safety Considerations

Limited trial data indicate that pexiganan cream is generally well tolerated. Rates of worsening cellulitis (2‑4 %) and amputation (2‑3 %) were similar to those seen with oral ofloxacin. No serious adverse events were reported, and no resistance to pexiganan emerged during the studies. Long‑term safety and systemic toxicity have not been established.

How It Is Administered

Pexiganan is formulated as a 1 % topical cream applied directly to the infected ulcer surface. The route of administration is topical; systemic absorption is minimal, and dosing regimens have been studied only in the context of short‑term ulcer treatment.

Routes of Administration

Goals & Uses

• Diabetic foot infectionInfectious DiseaseModerate
• Reduction of antibiotic resistance riskAntibiotic StewardshipLow
• Treatment of infected diabetic foot ulcersInfectious Disease / Wound CareModerate
• Broad-spectrum antibacterial activityAntimicrobialModerate
• Avoidance of systemic antibiotic exposureAntibiotic StewardshipModerate

Contraindications

• Hypersensitivity to pexigananAllergyHigh
• Application to deep or tunneling woundsWound CharacteristicsModerate
• Known hypersensitivity to pexiganan or excipientsAllergyHigh

Adverse Effects

• Contact dermatitisDermatologicalUncommon
• Systemic absorption-related effectsSystemicRare
• Application site painLocalCommon
• Application site irritationLocal/dermatologicalCommon
• Application site erythemaLocalCommon

Drug Interactions

• Other topical antimicrobialsLow

Population Constraints

• Patients with severe or deep foot infectionsDisease SeverityRelative
• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative
• Pediatric useAgeRelative

Regulatory Status

• European UnionUnapprovedNo marketing authorization granted.
• United StatesInvestigationalFDA did not approve; development discontinued.
• United KingdomUnapprovedNot approved by MHRA.

Not approved by FDA or EMA; development halted.

Evidence & Sources

• Pexiganan acetate
  Journal ArticleModerateLamb HM, Wiseman LR1998-01-01T00:00:00.000000Z
• Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream
  Journal ArticleModerateLipsky BA, Holroyd KJ, Zasloff M2008-01-01T00:00:00.000000Z
• Systematic review of antimicrobial treatments for diabetic foot ulcers
  Journal ArticleHighNelson EA, et al.2006-01-01T00:00:00.000000Z
• Rational design of stapled antimicrobial peptides
  Journal ArticleModerateYou Y, et al.2023-01-01T00:00:00.000000Z
• Topical antimicrobial agents for treating foot ulcers in people with diabetes
  Journal ArticleHighDumville JC, et al.2017-01-01T00:00:00.000000Z
• Structure, membrane orientation, mechanism, and function of pexiganan--a highly potent antimicrobial peptide designed from magainin
  Journal ArticleModerateGottler LM, Ramamoorthy A2009-01-01T00:00:00.000000Z

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