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Polymyxin B: The 1950s Peptide Antibiotic Brought Back for Resistant Infections — What It Is and What Its Label Warns

Polymyxin B is a cyclic peptide antibiotic with a fatty tail, made by the soil bacterium Bacillus polymyxa. It attacks the outer membrane of Gram-negative bacteria. Most of its US products are eye and ear drops that combine it with other antibiotics; the injection carries a boxed warning for kidney and nerve toxicity and is now used as a last resort against resistant infections.

FDA-approved (since the 1960s)Cyclic lipopeptide antibioticInjection, eye and ear drops

Caroline S · Published 2026-10-14

Length

A cyclic peptide with a long fatty-acid tail (ChEBI); the main component, polymyxin B1, is C56H98N16O13, mass 1,203.5, with a 6-methyloctanoyl group at its amino end (ChEBI:8309)

Sequence

Polymyxin B sulfate is the sulfate salt of polymyxins B1 and B2, a mixture rather than one molecule (label); B1 and B2 differ in the fatty acid on the chain's start

Origin

Produced by the soil bacterium Bacillus polymyxa (label). Oldest US application in Drugs@FDA: Maxitrol eye drops (with neomycin and dexamethasone), NDA 050023, 1963-06-06; first injection application listed, ANDA 060716, 1964-06-29 (now discontinued)

Last reviewed

2026-10-14

What is it good for?

Treating serious infections with Gram-negative bacteria — the injection label names Pseudomonas aeruginosa infections of the urinary tract, meninges and bloodstream — and, much more commonly, eye and ear infections in combination drops and ointments with other antibiotics or steroids.

Illustration: A clear glass vial with pale green crystalline powder on a white lab bench, copper reflections.
Illustration

What it is

Polymyxin B is a ring-shaped peptide with a fatty-acid tail, made by a soil bacterium. The injection label calls it "one of a group of basic polypeptide antibiotics derived from B polymyxa." What is sold is not one molecule but a mixture — as is the anticancer antibiotic bleomycin: polymyxin B sulfate is "the sulfate salt of Polymyxins B1 and B2" (label). The main component, polymyxin B1, has the formula C56H98N16O13 (mass 1,203.5) and a 6-methyloctanoyl fatty acid at the start of its chain (ChEBI:8309).

ChEBI describes the whole family as antibiotics with "a cyclic peptide with a long hydrophobic tail." That design — a positively charged peptide ring plus a greasy tail — is shared with daptomycin, which targets the opposite kind of bacteria.

How it works

Polymyxins "disrupt the structure of the bacterial cell membrane by interacting with its phospholipids" and are "selectively toxic for Gram-negative bacteria" (ChEBI). Gram-negative bacteria wrap their thin cell wall in an outer membrane, and that membrane is the target; the label's word "basic" means the peptide carries positive charges. Because polymyxin B does not cover Gram-positive germs, combination eye products pair it with bacitracin, whose label describes activity against most Gram-positive bacteria.

Units, not milligrams

Polymyxin B is dosed by potency. The label converts: 1 mg of pure polymyxin B base = 10,000 units, and each injection vial contains 500,000 units. The 2019 international consensus guidelines on the polymyxins name "several different conventions used to describe doses" among the reasons for "significant confusion" in their use (Tsuji et al., Pharmacotherapy 2019, PMID 30710469). Doses on the label are adjusted for kidney function and are decided by the treating team.

Mostly an eye and ear medicine

Our count of the 27 polymyxin B applications in Drugs@FDA (openFDA, 2026-10-14):

Product type Listings Typical partners
Eye drops and ointments (combinations) 13 trimethoprim; neomycin + bacitracin or gramicidin; neomycin + dexamethasone or hydrocortisone
Ear drops (combinations) 7 neomycin + hydrocortisone
Irrigation solutions (combinations) 2 neomycin
Single-ingredient injection 5 — (4 prescription, the oldest, from 1964, discontinued)

So the molecule most people meet is in an eye or ear drop, not a vein. The oldest application listed is Maxitrol eye drops, NDA 050023, dated 1963-06-06.

The injection and its boxed warning

The injection label names Pseudomonas aeruginosa infections of the urinary tract, meninges and bloodstream, and, "when less potentially toxic drugs are ineffective or contraindicated", certain infections with H. influenzae, E. coli, Aerobacter aerogenes and Klebsiella pneumoniae. For meningitis it "should be administered only by the intrathecal route" — into the spinal fluid.

The boxed warning, summarised as the label states it:

  • Hospital only when given into muscle or the spinal fluid, under constant supervision.
  • Kidney toxicity: albuminuria, cellular casts and azotaemia; "diminishing urine output and a rising BUN are indications for discontinuing therapy." Dosage is reduced in kidney damage.
  • Nerve toxicity: irritability, weakness, drowsiness, numbness, blurred vision, and respiratory paralysis from neuromuscular blockade, especially soon after anaesthesia or muscle relaxants.
  • Avoid combining with other kidney- or nerve-toxic drugs, naming bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin and colistin.
  • Pregnancy: "safety … has not been established."

The label is an older-format label with no randomised-trial section. The guideline authors make the same point about the whole class: the polymyxins "became available in the 1950s and thus did not undergo contemporary drug development procedures," and their recent return is "as salvage therapy for otherwise untreatable gram-negative infections."

Where it stands

  • Approved in the US since the 1960s; 27 applications in Drugs@FDA, 22 of them combination eye, ear or irrigation products (openFDA, 2026-10-14).
  • Guidelines: the 2019 international consensus guidelines (ACCP, IDSA, ISAP, SCCM, SIDP; endorsed by ESCMID, conclusions endorsed by EUCAST) were described by their authors as the first consensus recommendations for colistin and polymyxin B.
  • Research record: PubMed indexes 8,142 records for "polymyxin B", 167 tagged as randomised trials (2026-10-14).

Polymyxin B's most common partner in eye ointments is bacitracin. Two other bacterial peptide antibiotics in the library are daptomycin, a lipopeptide for Gram-positive infections, and the hospital glycopeptide vancomycin, which blocks cell-wall building. An approved drug that is a random mixture of four-amino-acid chains rather than a few defined components is glatiramer acetate (Copaxone).

What the research shows

Treats Pseudomonas aeruginosa infections of the urinary tract, meninges and bloodstream

FDA-labelled indication of the injection; the label is an older-format label with no modern randomised trial section

Treats infections resistant to newer antibiotics

Not a labelled claim; it is the use that drove its return. The 2019 international consensus guidelines (ACCP, IDSA, ISAP, SCCM, SIDP; ESCMID-endorsed) describe polymyxins as 'salvage therapy for otherwise untreatable gram-negative infections'

Treats eye and ear infections (in combination products)

FDA-approved combination products with trimethoprim, neomycin, bacitracin, gramicidin and/or corticosteroids (Drugs@FDA)

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

United States

27 applications in Drugs@FDA: 13 ophthalmic combination, 7 ear-drop combination and 2 irrigation combination product listings, and 5 single-ingredient injection applications, 4 listed as prescription (openFDA, our count, 2026-10-14).

Boxed warning (injection)

Kidney toxicity, nerve toxicity including respiratory paralysis, hospital-only use when given into muscle or the spinal fluid (label).

Published record

PubMed: 8,142 records for 'polymyxin B', 167 tagged as randomised controlled trials (2026-10-14).

Frequently asked questions

Is polymyxin B a peptide?

Yes. The label calls it a basic polypeptide antibiotic, and the ChEBI chemical database describes the polymyxins as a cyclic peptide with a long fatty tail. Like other bacterial peptide antibiotics it includes non-standard building blocks, and the drug is a mixture of two close variants, polymyxin B1 and B2.

What is polymyxin B used for?

Most often, as one ingredient of eye and ear drops or ointments — with trimethoprim, neomycin, bacitracin or a steroid. As an injection, the label names Pseudomonas aeruginosa infections of the urinary tract, meninges and bloodstream; in practice it is reserved for Gram-negative infections resistant to newer antibiotics, the role the 2019 consensus guidelines describe as salvage therapy.

Is polymyxin B the same as colistin?

No, but they are close relatives. Colistin is polymyxin E, also made by Bacillus polymyxa; the 2019 consensus guidelines cover both because they share a mechanism and a toxicity profile. For injection, colistin is given as colistimethate sodium, a chemically modified form (ChEBI), while polymyxin B is injected as polymyxin B sulfate.

Why is polymyxin B dosed in units?

Because it is a natural mixture whose activity was standardised by potency rather than weight. The label converts: 1 mg of pure polymyxin B base equals 10,000 units. The 2019 guidelines name the coexistence of different dose conventions as a source of confusion in using the polymyxins.

Why does polymyxin B harm the kidneys?

The label reports kidney toxicity — protein and casts in the urine, rising blood urea — and says diminishing urine output and a rising BUN are reasons to stop. It also warns against combining it with other drugs toxic to the kidneys or nerves, naming bacitracin, several aminoglycosides and colistin. The label does not give a mechanism.