Polymyxin B

Polymyxin B from Bacillus polymyxa is a detergent-like molecule: five free amino groups give it a strong positive charge that binds the anionic phosphate groups of lipid A in lipopolysaccharide, competitively displacing the calcium and magnesium that bridge adjacent LPS molecules. The outer membrane destabilises, the drug crosses it, and the inner membrane is then permeabilised. There is a secondary anti-endotoxin effect from direct LPS neutralisation, which is why polymyxin B haemoperfusion columns were trialled in septic shock. Resistance arises through mcr plasmid genes and chromosomal pmrAB/phoPQ mutations that add cationic groups to lipid A and repel the drug. Unlike colistin, polymyxin B is given as the active drug rather than an inactive prodrug, so it reaches target concentrations faster and is preferred for bloodstream infection.

Targets: Lipid A / lipopolysaccharide, Gram-negative outer membrane, Bacterial inner membrane

• · Polymyxin B is dosed in units, not milligrams: 15,000-25,000 units/kg/day of total body weight, divided every 12 hours. One milligram equals roughly 10,000 units, so a 70 kg adult receives about 1.0-1.75 million units per day, or 100-175 mg. Unlike almost every other antibiotic, the maintenance dose is NOT reduced for renal impairment.
• · 20,000-25,000 units/kg as a single load, endorsed by the 2019 international consensus guidelines to reach therapeutic exposure on day one.
• · Polymyxin B appears at 5,000-10,000 units per gram or millilitre in over-the-counter triple antibiotic ointments and prescription eye drops, usually with neomycin, bacitracin or gramicidin. Systemic absorption from intact skin is negligible.

Work out your exact syringe units →

• very commonNephrotoxicity— Acute kidney injury occurs in roughly 20-40% of treated patients and is the dose-limiting toxicity of the entire polymyxin class. Usually reversible if caught, but not always.
• commonNeurotoxicity - perioral and peripheral paraesthesia— Tingling around the mouth, face and extremities, plus dizziness and ataxia. Dose-related and reverses on stopping.
• commonHyperpigmentation— Darkening of the head, neck and upper trunk, more frequent in polymyxin B than colistin, appearing within days to weeks. It fades slowly after therapy.
• uncommonInfusion-related histamine reactions— Flushing and itching with rapid infusion.
• uncommonContact dermatitis from topical products— More commonly attributed to the neomycin or bacitracin in the same ointment.
• rareNeuromuscular blockade and respiratory arrest— A genuine historical cause of death with this class, especially with concurrent neuromuscular blocking agents or in myasthenia gravis.

• Myasthenia gravis or other neuromuscular disorders — the neuromuscular blocking effect can precipitate respiratory failure.
• Concurrent use of other neuromuscular blocking agents without airway control.
• Known polymyxin hypersensitivity.
• Should not be chosen when a less toxic agent with documented in vitro activity is available; this is a salvage drug.

• cautionaminoglycosides — Additive nephrotoxicity and neuromuscular blockade; among the riskiest combinations in critical care.
• cautionvancomycin — Compounded renal risk when both are given to the same critically ill patient.
• conflictneuromuscular blocking agents — Potentiates paralysis and can prolong apnoea.
• redundantcolistin — Same mechanism, same toxicity profile. There is no reason to give both; polymyxin B is generally preferred for bloodstream infection and colistin for urinary tract infection.

• · Serum creatinine and urine output daily during therapy.
• · Neurological examination for paraesthesia, weakness and ataxia at each assessment.
• · Therapeutic drug monitoring is available in a handful of specialist centres but is not routine.
• · Serum electrolytes, since renal injury commonly disturbs potassium and magnesium.

Prescription-only injectable in the US, EU and elsewhere; low-concentration topical polymyxin B is available over the counter in combination ointments and drops.

• Tsuji et al. 2019, international consensus guidelines for the optimal use of the polymyxins (guideline)
• Polymyxin B for injection US prescribing information (label)
• Reviews of polymyxin nephrotoxicity incidence and risk factors (review)

Same mechanism as colistin - cationic binding to lipid A, displacement of stabilising cations, outer membrane disruption - but administered as the active drug rather than a prodrug, which removes the conversion delay that makes colistin dosing unpredictable.

The characteristic error is renal dose adjustment. Because polymyxin B is cleared non-renally, reducing the dose in renal impairment produces subtherapeutic exposure while doing nothing to protect the kidney - the reflex that is correct for almost every other nephrotoxic antibiotic is wrong here. The second is poor urinary penetration: it is a bad choice for urinary tract infection precisely where colistin is a reasonable one.

• Lipid A of Gram-negative LPS — Electrostatic

  Outer membrane permeabilisation

Rapid, with no prodrug lag.

• ?Therapeutic drug monitoring is not routinely available despite a narrow therapeutic index.