What it is
Colistin is polymyxin E — a ring-shaped peptide with a fatty-acid tail, made by the soil bacterium Bacillus polymyxa. It is the close relative of the antibiotic in the polymyxin B entry: same producer, same target, same warnings. What is sold is a natural mixture, chiefly colistin A (C52H98N16O13, molecular weight 1,155.4; PubChem CID 5311054) and colistin B, which differ only in the fatty acid at the start of the chain — 5-methylheptyl in A, 5-methylhexyl in B, as the injection label puts it.
Part of the ring is built from 2,4-diaminobutanoic acid (the label abbreviates it Dbu), an amino acid that never appears in human proteins.
Two forms: colistin and colistimethate
| Form | What it is | Where it is used |
|---|---|---|
| Colistin sulfate | the active antibiotic as a salt | in the US, Coly-Mycin S (approved 1962) |
| Colistimethate sodium | colistin with methanesulfonate groups added; "an inactive prodrug of colistin" (Bergen et al. 2006, PMID 16723551) | injection into a vein or muscle |
The US label describes colistimethate as "a polypeptide antibiotic with an approximate molecular weight of 1750" — heavier than colistin because of the added groups. Its doses are written as colistin base activity: each vial is "equivalent to 150 mg colistin base activity", and the label caps the daily total at 5 mg/kg with normal kidney function, reduced in kidney impairment. The 2019 consensus guidelines name "several different conventions used to describe doses" among the reasons the polymyxins are prone to dosing confusion (Tsuji et al., Pharmacotherapy 2019, PMID 30710469). Doses are decided by the treating team.
How it works
The label calls colistimethate "a surface active agent which penetrates into and disrupts the bacterial cell membrane." The target is the outer membrane of Gram-negative bacteria — the extra wrapping that Gram-positive germs lack. The resistance gene described below works by changing lipid A, a component of that membrane (Liu et al.), which is why the membrane is taken to be where colistin acts. The label lists bactericidal activity against Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, and states it is "not indicated for infections due to Proteus or Neisseria."
What the label warns
The colistimethate label (Xellia, effective 2024-08-29) is an older-format label with a warnings section rather than a boxed warning. In summary:
- Kidney toxicity, "probably a dose-dependent effect", reversible after stopping.
- Temporary nerve symptoms: numbness or tingling around the mouth and in the limbs, itching, vertigo, dizziness and slurred speech; the label advises against driving during therapy.
- Respiratory arrest "has been reported following intramuscular administration", and impaired kidney function "increases the possibility of apnea and neuromuscular blockade."
- C. difficile diarrhoea, as with nearly all antibiotics.
The half-life after injection is 2 to 3 hours in adults and children, including premature infants (label).
The resistance gene that made headlines
For years colistin worked because bacteria rarely became resistant in a way they could share. That changed with a 2015 report from China (Liu et al., Lancet Infect Dis 2016, PMID 26603172). The authors found a gene, mcr-1, carried on a plasmid — a loop of DNA bacteria pass to one another — that adds phosphoethanolamine to lipid A, the part of the membrane colistin grips. In mice, it "negated the efficacy of colistin." The gene turned up in:
| Sample source (China, 2011–14) | With mcr-1 |
|---|---|
| Raw meat | 78 of 523 (15%) |
| Animals | 166 of 804 (21%) |
| Inpatients with infection | 16 of 1,322 (1%) |
The authors wrote that its emergence "heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance." The large share in animals and meat compared with patients is the study's own figure; it does not by itself show where the gene began.
Where it stands
- Approved in the US since 1962; four applications in Drugs@FDA — three colistimethate injection generics and the colistin sulfate product Coly-Mycin S — with the original Coly-Mycin M injection discontinued (openFDA, 2026-10-26).
- Guidelines: the 2019 international consensus guidelines on the polymyxins (ACCP, IDSA, ISAP, SCCM, SIDP; endorsed by ESCMID) cover colistin and polymyxin B together.
- Research record: PubMed indexes 14,127 records for "colistin", 173 tagged as randomised trials; ClinicalTrials.gov lists 124 studies with colistin as an intervention (2026-10-26).
Related reading
Colistin's sibling, injected without a prodrug step, is polymyxin B and its boxed warning. Other bacterial peptide antibiotics in the library are bacitracin, the Gram-positive lipopeptide covered in daptomycin's entry and the hospital glycopeptide vancomycin.