Skip to content
FDA Approved Immune & Anti-Inflammatory

Polymyxin B

also known as: Poly-RX

The gram-negative last resort — a cyclic lipopeptide antibiotic revived from the 1950s as a critical weapon against carbapenem-resistant Acinetobacter, Pseudomonas, and Klebsiella.

A cyclic decapeptide with a fatty acid tail that disrupts gram-negative bacterial outer membranes by displacing divalent cations from lipopolysaccharide (LPS), and additionally neutralizes circulating endotoxin.

Mechanism of action

The cationic peptide ring displaces Ca²⁺ and Mg²⁺ from the anionic phosphate groups of lipid A in gram-negative LPS, destabilizing the outer membrane. Subsequent insertion of the fatty acid tail into the inner membrane causes permeabilization and cell death. Also binds and neutralizes free LPS (endotoxin), potentially reducing sepsis-associated inflammation.

Primary uses

  • Carbapenem-resistant gram-negative infections
  • Multidrug-resistant Pseudomonas aeruginosa
  • MDR Acinetobacter baumannii
  • Endotoxin neutralization (hemoperfusion)

Typical dosing

1.5–2.5 mg/kg/day divided every 12 hours (intravenous)

Nephrotoxicity and neurotoxicity are dose-limiting. Therapeutic drug monitoring increasingly used.

Regulatory status

FDA-approved (original approval 1964). Available as polymyxin B sulfate for injection. Used for multidrug-resistant gram-negative infections when no alternatives exist.

References

  1. [review] Zavascki AP, et al. "Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review." J Antimicrob Chemother, 2007;60:1206-1215.

Related peptides

Daptomycin

A last-resort lipopeptide antibiotic — the first-in-class cyclic peptide that kills MRSA and VRE by depolarizing bacterial membranes, without resistance through traditional mechanisms.

LL-37

The only human cathelicidin — an antimicrobial peptide with direct activity against bacteria, fungi, viruses, and biofilms, with additional roles in wound healing and immune signaling.

Pexiganan

A Xenopus-magainin-derived antimicrobial peptide (Locilex; Dipexium Pharmaceuticals / later acquired by PLx Pharma) developed for topical treatment of mildly infected diabetic foot ulcers. Twice rejected by the FDA — once in 1999 (Magainin Pharmaceuticals) and again in 2017 (Dipexium) after the OneStep-1 and OneStep-2 Phase 3 trials failed to show superiority over placebo cream. Instructive regulatory case study in antimicrobial peptide drug development.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.