Polymyxin B / Colistin
Polymyxin antibiotic
Also Polymyxin B, Colistin, Colistimethate, Colistimethate sodium, Coly-Mycin M, Coly-Mycin
- Evidence
- BSome human evidence
- FDA status
- FDA approvedas of 2026-10-27
- Route
- Intravenous
- Studies cited
- 1 human0 animal or cell
They are last-resort antibiotics for germs that resist other drugs. They were approved before modern trials, and the one big trial of 406 people showed adding another antibiotic did not help.
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Polymyxin B and colistin are the antibiotics of last resort for Gram-negative bacteria that have beaten carbapenems.
Studies say
The polymyxins kill multidrug-resistant Gram-negative bacteria and remain in use for lack of alternatives, but their approvals predate controlled trials and the one large RCT showed that adding meropenem does not improve outcomes.
Why grade B. The polymyxins were approved decades before randomized trials were required, so their efficacy rests on bacteriology and observational experience. The modern controlled evidence is mostly about how to use them: the AIDA trial randomized 406 patients with carbapenem-resistant Gram-negative infections to colistin alone or colistin plus meropenem and found no difference in clinical failure. Last-resort use is well established; what is missing is trial-grade proof of benefit against modern comparators. 12
FDA. Both are FDA-approved antibiotics. Injectable polymyxin B is approved for serious infections caused by susceptible Gram-negative bacteria, with a boxed warning about kidney toxicity, nerve toxicity and the risk of respiratory paralysis; colistimethate sodium for injection, first approved as Coly-Mycin M, is approved for acute or chronic infections due to susceptible Gram-negative bacilli, mainly Pseudomonas aeruginosa. Drugs@FDA lists the first polymyxin B injection approval in 1964 and Coly-Mycin M in 1970, and both drugs are now sold as generics.
Written from 2 cited sources. Fact-checked 2026-10-27: 12 claims checked, 0 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Serious infections that other antibiotics cannot treat
- Can a US doctor prescribe it?
- Yes, FDA approved for serious infections from germs they can kill.
- Properly tested in people?
- Partly: some human trials, with gaps. The main trial had 406 people.
Evidence checklist
- Randomised controlled trial AIDA randomised trial of colistin combinationsyes
- Human study over 100 people AIDA, 406 patientsyes
- More than one research group Article does not say who ran the trialno information
- Clinical outcomes, not surrogate markers Clinical failure and mortality assessedyes
- Human safety data beyond case reports Boxed warning; kidney and nerve toxicity knownyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Polymyxin B and colistin (polymyxin E) are cyclic peptide antibiotics first isolated from the soil bacterium Paenibacillus polymyxa in the late 1940s. They differ by a single amino acid. Polymyxin B is given as the active drug; colistin is usually given as colistimethate sodium, an inactive prodrug that the body converts to colistin. Both were approved in the 1950s and 1960s and then largely abandoned for systemic use in the 1970s because of kidney damage, once safer drugs arrived. 2
They returned in the 2000s as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales spread, because for many of those organisms the polymyxins were the only drugs still active. Polymyxin B is also found in over-the-counter topical products such as Neosporin, where toxicity is not an issue because it is not absorbed. 12
How it works
Polymyxins are positively charged molecules with a fatty tail. The charged ring binds to the negatively charged lipopolysaccharide that forms the outer membrane of Gram-negative bacteria, displacing the calcium and magnesium ions that hold the membrane together. The fatty tail then inserts into the membrane, which leaks and the cell dies. Because the target is the outer membrane itself and not an enzyme, resistance developed slowly, though plasmid-borne mcr genes that modify lipopolysaccharide now spread resistance between species. The same membrane-disrupting action on kidney tubule cells explains the main toxicity. 12
What human research shows
The largest randomized trial, AIDA, enrolled 406 patients in Israel, Greece and Italy with severe infections caused by carbapenem-resistant Gram-negative bacteria, mostly Acinetobacter baumannii. Patients received colistin alone or colistin plus meropenem. Clinical failure at 14 days occurred in 79 percent of the colistin group and 73 percent of the combination group, a difference that was not significant, and 28-day mortality was similar. The trial settled a long argument by showing that routine combination with a carbapenem does not help when the organism is resistant to it. 1
The approved indications in the labels rest on older case series and bacteriologic data and not on controlled trials, which was the standard at the time. 2
| Study | Model | Finding |
|---|---|---|
| AIDA trial | Humans, n=406, randomized, open-label, colistin versus colistin plus meropenem | Adding meropenem did not reduce clinical failure or mortality in carbapenem-resistant Gram-negative infections. 1 |
| Polymyxin B label clinical basis | Humans, uncontrolled series and bacteriologic data from the 1950s and 1960s | Approval and indications rest on susceptibility data and case experience, not randomized trials. 2 |
Safety
Kidney injury is the main problem: the polymyxin B label carries a boxed warning for nephrotoxicity and neurotoxicity, and the drug must be dosed to kidney function and monitored with daily kidney tests. Neurotoxicity ranges from tingling around the mouth and dizziness to, rarely, respiratory paralysis from neuromuscular blockade, which is why the label warns against combining polymyxins with other nerve- or kidney-toxic drugs. In the AIDA trial, which used colistin, high clinical failure and mortality rates reflected how sick the patients were as much as the drug. 12
Questions for your clinician
- Are there alternatives to polymyxins for my infection?
- How often will kidney function be checked?
- Does adding a second antibiotic help, given the AIDA result?
Questions people ask
What is the difference between polymyxin B and colistin?
They are near-identical cyclic peptides from the same bacterium, differing by one amino acid. Polymyxin B is given as the active drug and reaches steady blood levels quickly; colistin is given as colistimethate, an inactive prodrug that converts slowly and unpredictably, which makes colistin harder to dose. Colistimethate is excreted by the kidney and is preferred for urinary infections, while polymyxin B is often preferred for bloodstream infections. 12
Why are they called drugs of last resort?
Because of their kidney toxicity, they were set aside once aminoglycosides, cephalosporins and carbapenems were available. They came back only when bacteria resistant to all of those appeared, and they are reserved for infections where nothing else works. Newer agents such as ceftazidime-avibactam and cefiderocol have since taken over some of that role. 12
Should colistin be combined with another antibiotic?
The AIDA trial, the largest randomized test of that question, found no benefit from adding meropenem to colistin for carbapenem-resistant infections. Test-tube evidence that the two drugs kill bacteria better together did not translate into better outcomes in patients. 1
Is the polymyxin B in Neosporin dangerous?
No. Topical polymyxin B is not absorbed through intact skin in meaningful amounts, so the kidney and nerve toxicity that limit the injectable form do not apply. 2