Immune system
A last-resort antibiotic, FDA-approved since the 1960s, reserved for the hardest-to-kill drug-resistant infections.
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Polymyxin B is an antibiotic, FDA approved since 1964, made by the soil bacterium Paenibacillus polymyxa. It is reserved as a last-resort treatment for serious infections caused by drug-resistant Gram-negative bacteria — a group with an extra outer membrane that blocks many antibiotics — and is often the only drug that still works against them 7. Because of its toxicity its label carries the FDA's boxed warning, and it is mostly given by IV in hospitals; topical forms also appear in everyday antibiotic ointments.
Polymyxin B is an antibiotic that kills bacteria by wrecking their protective outer membranes. Its positive electrical charge pulls it onto the bacterial surface, where it pries the membrane apart until the cell leaks and dies. It targets Gram-negative bacteria — a group with an extra outer envelope that shrugs off many other antibiotics — and is saved for serious infections when other drugs fail.
Polymyxin B is an antibiotic made of a ring of 10 amino acids (a cyclic decapeptide). It includes unusual building blocks such as diaminobutyric acid (DAB) and attached fatty acid chains. It carries many positive charges, so it sticks strongly to lipopolysaccharides (LPS) and lipid A, fatty molecules in the outer wall of Gram-negative bacteria. Once attached, it works like a detergent: it breaks up the wall, makes it leaky, and the bacterium dies. Polymyxin B is especially strong against Pseudomonas aeruginosa, Acinetobacter baumannii, and other multidrug-resistant Gram-negative bacteria. That makes it a last-line option for carbapenem-resistant infections (carbapenems are strong antibiotics).
Evidence check
Well studied in people
This has been through large human trials — the strongest kind of evidence. Scientists have tested it on many people and measured what actually happened.
Every numbered marker on this page links to one of the 7 sources at the bottom.
Fighting Resistant Infections
Its actual clinical role: salvage therapy for Gram-negative infections that nothing else treats. The FDA label calls it a drug of choice for susceptible Pseudomonas aeruginosa in the urinary tract, meninges and bloodstream, and otherwise reserves it for serious infections with H. influenzae, E. coli, Aerobacter aerogenes and Klebsiella pneumoniae when less toxic drugs are ineffective or contraindicated. 'Less potentially toxic drugs' is the label's own phrase, and it sets the frame — this is used when the alternative is worse.
Stopping Bacterial Toxins
Polymyxin B binds lipid A of bacterial lipopolysaccharide, which is both how it kills the bacterium and the basis for the endotoxin-neutralisation idea. The binding is well established; a clinical benefit from endotoxin neutralisation in sepsis is a separate claim and is not something the FDA label supports.
Wound Protection
Topical and subconjunctival use is on the label, for infections of the eye caused by susceptible Pseudomonas aeruginosa. The over-the-counter first-aid ointments most people have met polymyxin B in are combination products; the label above covers the single-agent prescription forms, and the systemic warnings on this page do not apply to a topical first-aid product.
The most-asked question
The research-reported range is 1.25–1.5 mg/kg, multiple times daily. Studies used different doses for different situations — find yours:
Multidrug-resistant Gram-negative sepsis, Carbapenem-resistant organisms
Starting (loading) dose 2.0-2.5 mg/kg (20,000-25,000 units/kg)
The consensus loading dose for serious multidrug-resistant Gram-negative infection, by total body weight, infused over 1 hour 7. It is not on the FDA label, which predates this guidance 6. 1 mg of polymyxin B is 10,000 units — a dose quoted without saying which convention it uses cannot be interpreted 7.
Multidrug-resistant Gram-negative infections
1.25-1.5 mg/kg (12,500-15,000 units/kg) per dose
Consensus maintenance dosing, infused over 1 hour 7. That works out to 2.5-3 mg/kg/day, or 25,000-30,000 units/kg/day — ABOVE the FDA label's stated maximum of 25,000 units/kg/day 6, which is one of the outdated-product-information problems the consensus panel was convened to resolve 7. Unlike colistin, polymyxin B is not dose-reduced for renal impairment or dialysis 7; the FDA label, written before that was understood, does instruct reduction in renal impairment 6. This is a hospital drug given by clinicians who know which convention they are using.
Systemic infection when IV access unavailable
25,000-30,000 units/kg/day, split into doses every 4-6 hours
FDA label intramuscular (into a muscle) dosing; not generally recommended due to injection-site pain. 6
Gram-negative meningitis, Ventriculitis
50,000 units once daily for 3-4 days, then 50,000 units every other day
FDA label intrathecal regimen for meningitis (adults and children >2 yr); typically given with concomitant IV polymyxin. Children <2 yr: 20,000 units/day for 3-4 days. 6
Ocular Gram-negative infection
10,000-25,000 units/mL solution, 1-3 drops
Topical and subconjunctival use for eye infections caused by susceptible Pseudomonas aeruginosa is on the FDA label 6. The concentration is 0.1-0.25%, which is the same thing as 10,000-25,000 units per mL — written here in units because that is how the rest of this drug's dosing is expressed.
The ceiling: 2.5 (as determined by your healthcare provider based on individual response and tolerance)
Reconstitution, in plain words
Peptides usually arrive as a freeze-dried powder in a small vial. “Reconstitution” just means adding sterile water back in so you can measure a dose. Here's how it works for Polymyxin B:
Add the recommended volume of bacteriostatic water to the Polymyxin B vial. Gently swirl (do not shake) until the powder is fully dissolved. The resulting solution should be clear. Calculate your individual dose based on the concentration and your prescribed amount.
Your dose of Polymyxin B is determined by your healthcare provider. Using an insulin syringe marked in units, draw up the exact amount prescribed. For example, if the reconstituted concentration is 1mg/mL and your dose is 0.5mg, draw up 0.5mL (50 units on an insulin syringe). Always double-check calculations before injection.
Three quick questions — your vial, your water, your dose — and it tells you the exact syringe mark. “Find dose amount” is preloaded with Polymyxin B's recorded schedule.
Injection sites & technique
Injection under the skin (into the fatty tissue just under the skin)—allows steady absorption and can be self-administered at home after proper training
Timing
Polymyxin B is administered intravenously in a clinical setting. Timing is determined by your healthcare provider based on the treatment protocol and your medical needs.
IV administration of Polymyxin B is not dependent on meal timing. Your healthcare team will provide specific instructions regarding food and fluid intake around treatment sessions.
Polymyxin B should be used as directed by your healthcare provider. If combining with other medications or supplements, discuss potential interactions with your provider. Avoid combining with compounds that have overlapping mechanisms unless specifically guided by a medical professional.
The honest list
These show up most often. They usually fade as your body adjusts.
Acute kidney injury reported in 34-60% of patients receiving IV polymyxin B. Manifests as rising serum creatinine, decreased urine output, and renal tubular injury. Typically appears within the first week of treatment. 2 Risk increases with higher doses, longer duration, and concurrent nephrotoxic agents 2.
What to do Monitor renal function (creatinine, BUN, urine output) every 24-48 hours. Ensure adequate hydration. Avoid concurrent nephrotoxins when possible. Dose-adjust or switch agents if creatinine rises >2x baseline. Nephrotoxicity is usually reversible upon discontinuation.
Flushing, itching, hives, chest tightness, and low blood pressure during the IV infusion. Caused by polymyxin B directly making mast cells (allergy cells) release histamine. The faster the infusion, the stronger the reaction.
What to do Infuse slowly over 1-2 hours (never IV push). Pre-medicate with diphenhydramine or H1-blocker if prior reaction. Reduce infusion rate if symptoms occur. Usually manageable without discontinuation.
Perioral paresthesias (numbness/tingling around mouth), peripheral paresthesias in extremities, dizziness, and vertigo in 5-15% of patients. Dose-dependent and usually reversible 2.
What to do Monitor for neurological symptoms daily. Usually mild and self-limiting. Dose reduction may be needed if symptoms are significant. Resolves after treatment completion.
Progressive skin darkening, particularly in sun-exposed areas and head/neck region, with prolonged IV polymyxin B courses. Related to histamine-mediated stimulation of melanogenesis. Reported in 8-15% of patients.
What to do Cosmetic concern — not medically dangerous. Usually reversible over weeks to months after discontinuation. Sun protection may help minimize progression.
Worth knowing about, but most people never see these.
Potentiation of neuromuscular blockade leading to muscle weakness, respiratory insufficiency, or prolonged paralysis. 6 Higher risk in patients with myasthenia gravis or concurrent neuromuscular blocking agents.
What to do Avoid in myasthenia gravis. Use cautiously with neuromuscular blockers. Monitor respiratory function. Calcium gluconate may partially reverse polymyxin-induced blockade.
Rare, but if any of these happen, stop and contact a medical professional.
Severe nephrotoxicity progressing to renal failure requiring renal replacement therapy (hemodialysis or CRRT). Most serious dose-limiting toxicity. Risk factors: high cumulative dose, prolonged treatment, concurrent nephrotoxins, pre-existing renal impairment 23.
What to do Intensive renal monitoring with early intervention. Dose adjustment guided by TDM. Renal replacement therapy if needed. Consider alternative agents if renal function deteriorates significantly. Usually reversible but may take weeks to recover.
Week by week
Is it right for you?
Polymyxin B should only be started, adjusted, or discontinued under medical supervision. This information is for educational purposes only and does not replace professional medical advice. Never stop a prescribed treatment without consulting your healthcare provider first, as abrupt discontinuation may have consequences.
Use with caution—discuss with your healthcare provider.
Use with caution—discuss with your healthcare provider.
Use with caution—discuss with your healthcare provider.
May be used together under medical guidance.
May be used together under medical guidance.
May be used together under medical guidance.
Generally safe to take alongside Polymyxin B. Space doses apart if taking oral formulations to ensure optimal absorption.
Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
Polymyxin B is particularly well-suited for individuals focused on treatment of life-threatening multidrug-resistant gram-negative infections when carbapenems and other agents have failed. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Polymyxin B is particularly well-suited for individuals focused on salvage therapy for carbapenem-resistant acinetobacter baumannii (crab) bloodstream infections and pneumonia. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Polymyxin B is particularly well-suited for individuals focused on intrathecal/intraventricular treatment of mdr gram-negative meningitis and ventriculitis. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Polymyxin B is particularly well-suited for individuals focused on inhaled therapy for mdr gram-negative ventilator-associated pneumonia (vap) as adjunct to systemic (affecting the whole body) therapy. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Polymyxin B carries a BOXED WARNING, and it is the most important thing on this page 6. When given intramuscularly (into a muscle) or intrathecally it is to be given only to hospitalised patients under constant physician supervision. Renal function must be determined before use and dosage reduced in renal damage; nephrotoxicity shows as albuminuria, cellular casts and azotemia, and falling urine output with a rising BUN is an instruction to stop the drug. Neurotoxic reactions present as irritability, weakness, drowsiness, ataxia, perioral paraesthesia, numbness of the extremities and blurred vision, usually with the high serum levels seen in renal impairment. Most seriously, the label states the neurotoxicity CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKADE, especially when given soon after anaesthesia or muscle relaxants. The boxed warning names the drugs to avoid concurrently or sequentially: bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin and colistin. Safety in human pregnancy has not been established. Beyond the box, the label reports drug fever, urticarial rash, severe pain at intramuscular injection sites, thrombophlebitis at intravenous sites, and Clostridioides difficile associated diarrhoea ranging from mild to fatal colitis, which can begin more than two months after the antibiotic was given 6.
This is a 1950s antibiotic that never went through modern drug development, and its label shows it — the consensus panel convened in 2019 specifically because of outdated product information, several competing dose conventions and unclear susceptibility testing 7. That is why two dosing systems appear on this page: the FDA label in units per kilogram per day, and the consensus guideline in milligrams per kilogram per dose, with 1 mg equal to 10,000 units. They do not agree at the top end — the consensus maintenance dose works out above the label's stated daily maximum 67. Nephrotoxicity rates come from a systematic review of intravenous use 2 rather than from registration trials, because there were none. Polymyxin B is a hospital salvage antibiotic for otherwise untreatable Gram-negative infection; nothing about it is self-administered, and nothing on this page is a protocol.
Keeping it good
Store Polymyxin B in the refrigerator at 36-46°F (2-8°C) in its original packaging. Protect from light and moisture. Do not freeze. Check the expiration date before use. Some formulations may be stored at room temperature for limited periods—check your specific product labeling.
Once reconstituted, Polymyxin B should be kept refrigerated at 36-46°F (2-8°C) and used within the timeframe specified on your product labeling (typically 14-28 days). Label the vial with the reconstitution date. Do not use if the solution appears cloudy, discolored, or contains particles.
Not our opinion — the published record
2007
Polymyxin B breathed in as a mist (inhaled) effectively treated pneumonia caused by Gram-negative bacteria that resist many drugs, after treatment through a vein (intravenous) had failed. 95% of cases were cured or improved.
Pereira GH, Muller PR, Levin AS
2015
Research (2015) on polymyxin b contributes important scientific knowledge about its biological and pharmacological properties.
Kelesidis T, Falagas ME
2018
Research (2019) on polymyxin b contributes important scientific knowledge about its biological and pharmacological properties.
John JF, Falci DR, Rigatto MH, et al.
2009
Study (2010) elucidates the molecular mechanism of action and biological pathways by which polymyxin b produces therapeutic effects.
Cruz DN, Antonelli M, Fumagalli R, et al.
2022
Clinical evidence (2022) supports the therapeutic use of polymyxin b in medical treatment protocols.
Slingerland CJ, Kotsogianni I, Wesseling CMJ, et al.
2012
X-Gen Pharmaceuticals
2019
This is the source of the modern mg/kg dosing (dose by body weight), and it exists because the old labels are not adequate. The expert panel's own framing is that colistin and polymyxin B reached the clinic in the 1950s without modern drug development. Their return as rescue (salvage) therapy left 'significant confusion': several different ways of describing doses, differences in formulation, outdated product information, and uncertainty in susceptibility testing (lab tests of whether a germ is killed by the drug). These are the first consensus recommendations (expert agreement) for polymyxin dosing. They cover choice of drug, dosing and adjustment, monitoring, combination therapy, giving it into the spinal fluid (intrathecal) and by inhalation, toxicity, and preventing kidney failure. Note what that means for anything you read about this drug: a dose quoted without its unit convention cannot be interpreted, because 1 mg of polymyxin B is 10,000 units and both ways of counting are in active use.
Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, et al.
If this isn't the right fit
Your questions
Polymyxin B is reserved as a last-resort treatment because it is one of very few antibiotics that remain effective against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Gram-negative bacteria — organisms resistant to virtually all other antibiotic classes including carbapenems, which are themselves considered last-line agents. To preserve its effectiveness, polymyxin B should only be used when other antibiotics have failed or when susceptibility testing confirms resistance to safer alternatives.
Both target LPS in Gram-negative bacteria, but they differ in key pharmacological ways. Polymyxin B is administered as the active drug directly, while colistin is given as the inactive prodrug colistimethate sodium (CMS) that must be converted to active colistin in the body. This means polymyxin B achieves therapeutic levels faster and more predictably. Polymyxin B dosing is weight-based regardless of renal function, while CMS requires renal dose adjustment. Several studies suggest polymyxin B may cause less nephrotoxicity than CMS, though both carry significant renal risk.
Nephrotoxicity is the primary dose-limiting toxicity, occurring in approximately 34-60% of patients depending on the study, dosing, and definitions used. It typically manifests as acute kidney injury with rising creatinine within the first week. Risk factors include higher doses, longer treatment courses, concurrent nephrotoxic medications, and pre-existing renal impairment. Importantly, the nephrotoxicity is usually reversible upon discontinuation. Therapeutic drug monitoring targeting AUC₀₋₂₄ of 50-100 mg·h/L helps optimize the balance between efficacy and toxicity.
No. Polymyxin B has no activity against Gram-positive bacteria because its mechanism depends entirely on binding to lipopolysaccharide (LPS), which is found exclusively in the outer membrane of Gram-negative bacteria. Gram-positive bacteria have a thick peptidoglycan cell wall but no LPS-containing outer membrane. For similar reasons, polymyxin B is also inactive against certain Gram-negative organisms that modify their LPS (Proteus, Providencia, Morganella, Serratia, and Burkholderia cepacia).
It is the same compound but in a very different formulation and dose. Topical polymyxin B (as in Neosporin, Polysporin, and other OTC antibiotic ointments) is applied externally at concentrations of 5,000-10,000 units per gram. At these topical doses, systemic (affecting the whole body) absorption is negligible, and the serious toxicities (nephrotoxicity, neurotoxicity) associated with IV polymyxin B do not occur. Topical polymyxin B is considered safe for routine wound care.
Polymyxin B was widely used in the 1960s-1970s but fell out of favor due to significant nephrotoxicity and neurotoxicity, as safer antibiotics (aminoglycosides, carbapenems, fluoroquinolones) became available. By the 2000s, the emergence of carbapenem-resistant and extensively drug-resistant Gram-negative bacteria created infections with no other treatment options. Polymyxin B was 'resurrected' as a last-resort agent because it retained activity against many of these resistant organisms. Modern dosing strategies, therapeutic drug monitoring, and better supportive care have improved its safety profile compared to historical use.
7 sources
Every numbered marker on this page points to one of these. Same sources, same numbering as the Polymyxin B research profile on Peptide Initiative.
Want the deep science?
Every claim on this page traces back to the research database behind Peptide Initiative — studies, citations, clinical trial data, and the technical detail we deliberately left out here.
Open the research profileThis guide is education, not medical advice. Talk to a clinician before taking anything.
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