Polymyxin B

What it is

Polymyxin B is a last-resort hospital antibiotic given intravenously when multidrug-resistant Gram-negative bacterial infections — including those caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii — have failed all other treatments. It is also used in sepsis hemoperfusion devices to filter endotoxin from blood.

The scientific side

polymyxin B (PmB) is a cationic cyclic lipopeptide antibiotic that kills Gram-negative bacteria through a dual-stage mechanism targeting the bacterial cell envelope. The first stage is electrostatic: the positively charged amino groups of polymyxin B competitively displace divalent calcium and magnesium cations that normally stabilize lipopolysaccharide (LPS) in the outer membrane. This initial interaction is driven by high-affinity binding to the lipid A portion of LPS, which polymyxin B recognizes via its fatty acid tail and cyclic peptide ring. The second stage is mechanical disruption of membrane architecture. Molecular dynamics simulations show that PmB binding loosens the LPS bilayer by decreasing lipopolysaccharide tail order and creating packing defects, increasing outer membrane permeability. Crucially, a 2025 study demonstrated that metabolic activity is required for full lethality: PmB kills exponentially growing Escherichia coli but spares stationary-phase cells unless a carbon source is available. Antibiotic lethality at clinically relevant doses correlates with active LPS synthesis and transport, and energy-dependent outer membrane disruption — visualized as surface protrusions by atomic force microscopy — that enables PmB access to the inner membrane, which it subsequently permeabilizes in an energy-independent manner to cause cell death. On the inner membrane, coarse-grained simulations paradoxically show PmB stiffens the phospholipid bilayer by filling lipid packing defects and restricting lipid diffusion, rather than forming classical pores, contributing to biological inactivation of the cell. The high-affinity interaction with lipid A also underlies polymyxin B's endotoxin-neutralizing activity: immobilized polymyxin B fibers (PMX-F) are used in extracorporeal hemoperfusion cartridges to adsorb circulating LPS from blood in Gram-negative sepsis. Resistance emerges through modification of lipid A — particularly through mgrB insertional inactivation and pmrAB mutations in carbapenem-resistant Klebsiella pneumoniae — which reduce the negative charge of the LPS target, decreasing polymyxin binding. Unlike colistin (polymyxin E), polymyxin B is administered as the active drug rather than a prodrug, producing more predictable pharmacokinetics and a different nephrotoxicity profile.

Class: Cyclic lipopeptide antibiotic — polymyxin class; last-resort Gram-negative antimicrobial agent

What it's studied for

• Treatment of MDR and XDR Gram-negative bacterial infections (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) — systemic IV therapy Human observational
• Treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia — polymyxin B combination therapy Human observational
• Extracorporeal endotoxin removal in Gram-negative sepsis — polymyxin B hemoperfusion (PMX cartridge) Human observational
• Optimized dosing in critically ill patients including those on continuous renal replacement therapy (CRRT) Human observational
• Polymyxin B vs colistin comparative effectiveness and nephrotoxicity in MDR Gram-negative infections Human observational
• Treatment of MDR Pseudomonas aeruginosa and other Gram-negative infections in immunocompromised patients (e.g., renal transplant recipients) Human observational
• Mechanism of bacterial killing and investigation of polymyxin resistance — translational/mechanistic studies Mechanistic only

Safety signals

• Nephrotoxicity — acute kidney injury (AKI)
• Trough plasma concentration-dependent nephrotoxicity — elevated polymyxin B trough levels are an independent AKI risk factor, and maintaining trough levels below defined thresholds reduces the risk of AKI
• Skin hyperpigmentation — diffuse darkening of skin (especially face and forearms), peaking at approximately 2 weeks after initiation, with partial resolution after discontinuation
• Acquired Bartter syndrome — polymyxin B-induced renal tubular dysfunction presenting as chloride-unresponsive metabolic alkalosis, hypokalaemia, hypomagnesaemia, and hypercalciuria
• Neurotoxicity — peripheral neuropathy and neuromuscular blockade; risk of respiratory paralysis at high doses or in patients with compromised neuromuscular function
• Emergence of heteroresistance and full polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae during treatment — 76.62% of CRKP isolates showed clinically undetected heteroresistance before treatment, and 27.97% of heteroresistant strains evolved to full resistance after polymyxin B exposure
• Hypersensitivity reactions — rash, urticaria, anaphylaxis reported; intravenous infusion-related reactions

Community-reported dosing

All studies (5)

• PMID 10227782
• PMID 31812355
• PMID 34550139
• PMID 38295990
• PMID 41023239