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[Pharmacology](https://durgical.com/en/pharmacology/) · Class

# Polymyxins

Old, detergent-like antibiotics that punch holes in the gram-negative membrane; a last resort for multidrug-resistant bacteria, toxic to kidney and nerves.

Updated 2026-11-01

## What they are

Cationic cyclic peptides (polymyxin B and colistin, also called polymyxin E). They fell out of use because of toxicity and returned as a last resort against multidrug-resistant Pseudomonas, Acinetobacter and Enterobacterales.

## Mechanism of action

Polymyxins are surface-active, amphipathic peptides that act like detergents. They bind the lipid A portion of lipopolysaccharide in the gram-negative outer membrane, interact with membrane phospholipids and disrupt the membrane, so the cell leaks and dies. Binding lipid A also neutralizes endotoxin.

Target: Lipid A of the lipopolysaccharide in the gram-negative outer membrane

## Key points

- Dose-related nephrotoxicity is the main limit; acute kidney injury is common.
- Neurotoxicity: perioral paresthesia, dizziness, slurred speech and neuromuscular blockade with apnea, worse with anaesthetics, muscle relaxants and aminoglycosides.
- Only gram-negatives; Proteus and Serratia are intrinsically resistant, as are Burkholderia.
- Colistin is given as the inactive prodrug colistimethate; polymyxin B is given in its active form.

## Drugs in this class

- [**Colistin (colistimethate)** A last-resort polymyxin for multidrug-resistant Pseudomonas, Acinetobacter and Klebsiella; it can injure the kidney… Lipid A of the lipopolysaccharide, gram-negative outer membrane](https://durgical.com/en/pharmacology/colistin/)
- [**Polymyxin B** A polymyxin given IV, IM or intrathecally for resistant gram-negatives, and used topically in eye and ear drops… Lipid A of the lipopolysaccharide, gram-negative outer membrane](https://durgical.com/en/pharmacology/polymyxin-b/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which bacterial structure do polymyxins attack?

The gram-negative outer membrane: they bind the lipid A of lipopolysaccharide and disrupt the membrane like a detergent.

## Which two organisms are naturally resistant to polymyxins?

Proteus and Serratia (Burkholderia as well).

## Why are polymyxins combined with aminoglycosides only with great caution?

Both damage the kidney and both block the neuromuscular junction, adding the risk of kidney failure and apnea.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 59 (McGraw Hill, 2023); [DailyMed - COLISTIMETHATE- colistimethate sodium injection, powder, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ec7dc90-825c-422e-9f4b-c8ace9d93af5) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - POLYMYXIN B- polymyxin b sulfate injection, powder, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b56f18c0-ef5e-4ed9-a5af-f79f3cd189b6) (DailyMed (U.S. National Library of Medicine), 2026).

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