Magainin
The frog-skin antibiotic that worked as well as a pill and was rejected anyway
Magainins were found in frog skin and became the template for pexiganan, a topical antibiotic cream for infected diabetic foot ulcers. It matched oral ofloxacin in trials and was not approved, which is the most instructive thing about it.
What is it?
Magainins were isolated from frog skin in the 1980s and became the best-known example of a natural antimicrobial peptide. They kill by breaking up bacterial membranes, which is why resistance to them is harder to select than resistance to a drug with one molecular target.
Pexiganan was the version taken into development, as a cream for mildly infected diabetic foot ulcers. Two phase 3 trials compared it with oral ofloxacin. One failed to show equivalence; the other, and the pooled data, did show it, with no significant difference in worsening cellulitis or amputation.
It was not approved, and the reason is worth stating plainly: matching an existing oral antibiotic is not the same as beating it, and regulators asked for more. The laboratory work kept going, including resistance-selection testing that found no significant resistance emerging to pexiganan in treated patients while resistance to ofloxacin did emerge in some.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
These are the studies, read from their PubMed abstracts: one clinical programme and the laboratory work around it.
Equivalent to an oral antibiotic, and not approved
Two phase 3 trials compared topical pexiganan cream with oral ofloxacin in mildly infected diabetic foot ulcers. Study 303 failed to show equivalence; study 304 and the pooled data did. Worsening cellulitis (2-4%) and amputation (2-3%) did not differ between arms. Resistance to ofloxacin emerged in some patients who received it, while no significant resistance to pexiganan emerged.
What it kills, and at what concentration
Against pathogens from diabetic foot infections, the all-organism MIC90 for pexiganan was 32 mcg/mL, more than 250-fold below the concentration in the cream being developed. Reduced vancomycin susceptibility did not affect its activity, while Enterococcus faecalis was intrinsically less susceptible.
Trying to breed resistance to it
Testing of pexiganan's bactericidal action and resistance selection, the question that matters most for a membrane-disrupting antibiotic.
The analogue's original profile
The in vitro antimicrobial activity of MSI-78, the magainin analogue that became pexiganan.
Against bacteria from real ulcers
Susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers, the organisms the cream was meant to treat.
Side Effects & Contraindications
Reported Side Effects
From the clinical programme; this was a topical product.
Contraindications & Cautions
Not an approved medicine anywhere.
Legal Status
Never approved.
Frequently Asked Questions
?What are magainins?
Antimicrobial peptides first isolated from frog skin that kill bacteria by disrupting their membranes.
?Did pexiganan work?
In two phase 3 trials against oral ofloxacin in mildly infected diabetic foot ulcers, one failed to show equivalence and the other, with the pooled data, did. It was not approved.
?Why does that matter?
Because matching an existing oral antibiotic is not the same as beating it. The case shows how high the bar is for a new topical antibiotic.
?Does resistance develop to it?
In the trials no significant resistance to pexiganan emerged among treated patients, while ofloxacin resistance did emerge in some.
References
- [pubmed] Lipsky BA, et al. "Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream." Clin Infect Dis, 2008;47(12):1537-45. PMID: 18990064.
- [pubmed] Flamm RK, et al. "In vitro spectrum of pexiganan activity when tested against pathogens from diabetic foot infections and with selected resistance mechanisms." Antimicrob Agents Chemother, 2015;59(3):1751-4. PMID: 25583717.
- [pubmed] Flamm RK, et al. "In vitro spectrum of pexiganan activity; bactericidal action and resistance selection tested against pathogens with elevated MIC values to topical agents." Diagn Microbiol Infect Dis, 2016;86(1):66-9. PMID: 27352729.
- [pubmed] Fuchs PC, et al. "In vitro antimicrobial activity of MSI-78, a magainin analog." Antimicrob Agents Chemother, 1998;42(5):1213-6. PMID: 9593152.
- [pubmed] Ge Y, et al. "In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers." Diagn Microbiol Infect Dis, 1999;35(1):45-53. PMID: 10529881.
- [pubmed] Zasloff M. "Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor." Proc Natl Acad Sci U S A, 1987;84(15):5449-53. PMID: 3299384.
- [pubmed] Zasloff M. "Antimicrobial peptides of multicellular organisms." Nature, 2002;415(6870):389-95. PMID: 11807545.
Sources & Citations
Studies were read from their PubMed abstracts on October 1, 2026; the US status was checked in Drugs@FDA the same day.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.