Overview

An antibiotic that was shelved for being too toxic and brought back because the alternative became no antibiotic at all. Its return is one of the clearest markers of how far Gram-negative resistance has progressed.

FDA ApprovedFDA-approved. Abandoned in the 1970s for toxicity, then reintroduced as a last-resort agent against multidrug-resistant Gram-negative organisms.

At a glance

Regulatory status	FDA-approved. Abandoned in the 1970s for toxicity, then reintroduced as a last-resort agent against multidrug-resistant Gram-negative organisms.
Drug class	Cyclic cationic polypeptide antibiotic with a fatty acyl tail
Route	Intravenous, inhaled, or topical
Half-life	~2–3 hours (colistin base, after conversion from the prodrug)
Evidence rating	4/5 Strong Evidence rating 4 out of 5: Strong Consistent human randomized trials, or approval outside the United States.
Studied in	Extensive observational and registry data in carbapenem-resistant infection; randomized trials comparing colistin monotherapy with combination regimens.

How it works

The polycationic peptide binds lipid A in the Gram-negative outer membrane, displacing the divalent cations that stabilise lipopolysaccharide. The membrane becomes permeable and the cell dies. The same affinity for anionic membranes explains its renal and neurological toxicity.

Evidence base

Rated 4 of 5 — Strong. Consistent human randomized trials, or approval outside the United States.

Largely observational modern evidence — it re-entered practice out of necessity rather than through a trial program.

Benefits & potential uses

Bars indicate how well each claim is supported: three = strong human evidence, two = moderate, one = preliminary or preclinical.

Activity against carbapenem-resistant organisms Moderate evidence

Retains activity against many multidrug-resistant Acinetobacter, Pseudomonas and Klebsiella isolates where nothing else works.
Inhaled delivery for lung infection Moderate evidence

Nebulised colistin achieves high airway concentrations with less systemic exposure, used particularly in cystic fibrosis.
Slow resistance development historically Moderate evidence

Decades of limited use kept resistance rates low, though the mobile mcr-1 resistance gene has changed that picture.
A genuine last-resort option Strong evidence

Sometimes the only in-vitro active agent available.

Risks, cons & cautions

Bars indicate seriousness: three = serious or common, two = moderate, one = minor.

Nephrotoxicity in a large fraction of patients Serious

Acute kidney injury occurs in a substantial proportion of treated patients and is the dominant limitation on its use.
Neurotoxicity Serious

Paraesthesia, dizziness, ataxia and, rarely, neuromuscular blockade causing respiratory arrest — particularly with concurrent neuromuscular blocking agents.
Confusing dosing units Serious

Colistimethate is dosed in international units in some countries and in colistin base activity milligrams in others. Unit confusion has caused serious dosing errors.
Prodrug pharmacokinetics Moderate evidence

Colistimethate must convert to active colistin, and conversion is slow and variable, complicating dosing in critical illness.
Emerging plasmid-mediated resistance Serious

The mcr-1 gene confers transferable colistin resistance and has spread internationally, largely driven by agricultural use.
Weak evidence base by modern standards Moderate evidence

Reintroduced without the trial program a new drug would require today.

Who should avoid it

Concurrent neuromuscular blocking agents where avoidable
Myasthenia gravis
Pre-existing severe renal impairment (dose adjustment mandatory)
Use when a less toxic active agent is available

If used under medical supervision, monitor

Serum creatinine daily in critical illness
Neurological examination for paraesthesia and weakness
Careful verification of dosing units
Culture and susceptibility to confirm no better option exists

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

Neuromuscular blocking agents — risk of prolonged paralysis and respiratory arrest
Aminoglycosides and vancomycin — additive nephrotoxicity
Loop diuretics — additive renal risk

Regulatory & legal status

Prescription antibiotic reserved for resistant infections.

Infographic

Colistin (Polymyxin E) — benefits & risks at a glance Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

antibioticlast resortmultidrug resistancepolypeptideapproved

Related peptides in Antimicrobial & Antibiotic

Terms used on this page

Endotoxin (Lipopolysaccharide): Endotoxin is the lipopolysaccharide of Gram-negative outer membranes, a heat-stable TLR4 agonist that causes fever and shock at nanogram doses and that sterilisation does not remove.
Fibrosis: Fibrosis is the accumulation of excess extracellular matrix that replaces functional tissue, representing repair that has failed to resolve rather than a separate disease process.

This page is educational information, not medical advice. It cannot account for your medical history, medications, or risk factors. Do not start, stop or change any treatment based on it. Speak to a qualified healthcare professional who knows your case.