Polymyxin B
Cyclic lipopeptide antibiotic from Paenibacillus polymyxa containing 10 amino acids with 6 diaminobutyric acid residues and a fatty acid tail — FDA-approved since 1964 as a last-resort treatment for multidrug-resistant Gram-negative infections including Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae, targeting lipid A of bacterial lipopolysaccharide with rapid bactericidal membrane disruption
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Suggested dose
1.25 mg/kg – 2.5 mg/kg
Compound profile
Scientific & efficacy data
Immune
Peptide profile
Strong human trials
Polymyxin B
Loading dose 2.0-2.5 mg/kg (20,000-25,000 units/kg) · Multiple times daily
Molecular formula
C₅₆H₉₈N₁₆O₁₃ (polymyxin B₁ free base)
- Mol. weight
- 1,203.5 g/mol (free base); ~1,385 g/mol (sulfate salt)
- CAS number
- 1405-20-5 (polymyxin B sulfate)
- PubChem
- 49800004
- Developed · 1947 (discovery); 1964 (FDA approval); 2000s (clinical resurgence for MDR Gram-negatives)
- Bacillus polymyxa (natural source); Colistin Industries
Colistin Industries / Hospira Pharmaceuticals
Amino acid sequence
Dab-Dab-Dab-Phe-Dab-Phe-Dab-Asp-Dab-Dab (cyclic with fatty acid)Fighting Resistant Infections
Its actual clinical role: salvage therapy for Gram-negative infections that nothing else treats [7]. 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 [6]. '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 [1]. 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 [6].
Wound Protection
Topical and subconjunctival use is on the label, for infections of the eye caused by susceptible Pseudomonas aeruginosa [6]. 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.
Dosing
How much do I take?
1.25 mg/kg – 2.5 mg/kg · intravenous
1.25 mg/kg – 2.5 mg/kg
Covers all 5 documented dose levels · 4 administration routes · timing · dose-adjustment guidance.
Suitability
Is this right for me?
Best for treatment of life-threatening multidrug-resistant gram-negative infections when carbapenems and other agents have failed & salvage therapy for carbapenem-resistant acinetobacter baumannii (crab) bloodstream infections and pneumonia
Best for
Treatment of life-threatening multidrug-resistant Gram-negative infections when carbapenems and other agents have failed
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.
Salvage therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections and pneumonia
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.
Intrathecal/intraventricular treatment of MDR Gram-negative meningitis and ventriculitis
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.
Inhaled therapy for MDR Gram-negative ventilator-associated pneumonia (VAP) as adjunct to systemic therapy
Polymyxin B is particularly well-suited for individuals focused on inhaled therapy for mdr gram-negative ventilator-associated pneumonia (vap) as adjunct to systemic therapy. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Consider alternatives if
Do not use if
Use with caution if
Not sure?
Compare Polymyxin B with similar peptides to find the best fit for your goals.
Administration
How do I use it?
Intravenous infusion (on the FDA label) · Intrathecal (the label's route of choice for Pseudomonas meningitis)
Route
Subcutaneous injection (into the fatty tissue just under the skin)—allows for consistent absorption and can be self-administered at home after proper training
Best sites
Covers reconstitution · step-by-step technique · storage · a sample daily schedule.
Safety
Is it safe?
4 common side effects · 2 serious
Polymyxin B carries a BOXED WARNING, and it is the most important thing on this page [6].
When given intramuscularly 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 [6][7]. 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.
Common side effects · experienced by some users
Nephrotoxicity
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. Risk increases with higher doses, longer duration, and concurrent nephrotoxic agents.
Management: 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.
Infusion-related histamine release
Flushing, pruritus, urticaria, chest tightness, and hypotension during IV infusion. Caused by direct polymyxin B-induced mast cell degranulation and histamine release. Dose-rate dependent.
Management: 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.
Neurotoxicity
Perioral paresthesias (numbness/tingling around mouth), peripheral paresthesias in extremities, dizziness, and vertigo in 5-15% of patients. Dose-dependent and usually reversible.
Management: Monitor for neurological symptoms daily. Usually mild and self-limiting. Dose reduction may be needed if symptoms are significant. Resolves after treatment completion.
Skin hyperpigmentation
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.
Management: Cosmetic concern — not medically dangerous. Usually reversible over weeks to months after discontinuation. Sun protection may help minimize progression.
Less common
These typically resolve with continued use or dose adjustment.
Stop and seek help if
- Severe or worsening side effects that don't improve with dose adjustment or supportive care
- Signs of an allergic reaction—rash, hives, swelling, or difficulty breathing
- Your healthcare provider recommends discontinuation based on your clinical response
- Development of any new medical condition that may be contraindicated with Polymyxin B
- Pregnancy or planning to become pregnant (unless specifically approved for use during pregnancy)
- Abnormal lab results or clinical markers that suggest adverse effects
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.
With other peptides
- Safe:Carbapenems (meropenem, imipenem — synergistic combination for carbapenem-resistant organisms; polymyxin disrupts outer membrane allowing carbapenem access to PBP targets) — May be used together under medical guidance.
- Safe:Rifampicin (strong synergy against A. baumannii — rifampicin inhibits RNA polymerase after polymyxin permeabilizes the outer membrane barrier) — May be used together under medical guidance.
- Safe:Minocycline or tigecycline (complementary mechanisms — tetracycline class inhibits protein synthesis while polymyxin disrupts membranes; effective combination for XDR A. baumannii) — May be used together under medical guidance.
With medications
- Caution:Aminoglycosides (gentamicin, tobramycin, amikacin) — additive nephrotoxicity and neurotoxicity; use combination only when absolutely necessary with intensive renal monitoring — Use with caution—discuss with your healthcare provider.
- Caution:Vancomycin at full doses — additive nephrotoxicity; if combination needed, monitor renal function daily — Use with caution—discuss with your healthcare provider.
- Caution:Neuromuscular blocking agents (succinylcholine, vecuronium) — polymyxin B potentiates neuromuscular blockade, risk of prolonged paralysis and respiratory failure — Use with caution—discuss with your healthcare provider.
With supplements
- Safe:Multivitamins — Generally safe to take alongside Polymyxin B. Space doses apart if taking oral formulations to ensure optimal absorption.
- Safe:Electrolyte supplements — Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
Effectiveness
How do I know it's working?
Strong human trials · first signs hours 0-24 (loading and early treatment)
Evidence level
Strong human trials
(Phase 3 or FDA approved)
Regulatory status
FDA approved
Indicated for acute infections caused by susceptible Pseudomonas aeruginosa (urinary tract, meninges, bloodstream), and for serious infections caused by H. influenzae, E. coli, Aerobacter aerogenes and Klebsiella pneumoniae when less toxic drugs are ineffective or contraindicated. Carries a BOXED WARNING. Meningeal infections must be treated by the intrathecal route only.
Onset of effects
Rapid
(hours to days)
How it works
Polymyxin B is a cationic antimicrobial peptide antibiotic that kills Gram-negative bacteria by destroying their protective cell membranes, used for serious infections when other antibiotics fail.
The deeper mechanism
Polymyxin B is a cyclic decapeptide antibiotic containing unusual amino acids including diaminobutyric acid (DAB) and fatty acid modifications.
Its highly cationic structure (from multiple positive charges) enables strong electrostatic binding to lipopolysaccharides (LPS) and lipid A components of Gram-negative bacterial outer membranes.
This binding initiates a detergent-like effect causing membrane disruption, increased permeability, and bacterial cell death.
Polymyxin B exhibits particularly potent activity against Pseudomonas aeruginosa, Acinetobacter baumannii, and other multidrug-resistant Gram-negative organisms, making it a last-line option for carbapenem-resistant infections.
What to expect
Hours 0-24 (loading and early treatment)
What you might notice
- Infusion-related reactions (flushing, pruritus) during IV administration
- Rapid bactericidal activity begins within hours of achieving therapeutic levels
- Perioral tingling or numbness may appear within first 24 hours
- Baseline laboratory values established for monitoring
What's normal
- Loading dose rapidly achieves therapeutic serum concentrations
- Infusion reactions are common and manageable with slow infusion rate
- Mild paresthesias are expected and dose-related
- Blood cultures should be repeated at 48-72 hours to assess microbiological response
What's next
- Transition to maintenance dosing (1.25-1.5 mg/kg q12h)
- Monitor renal function within 24-48 hours of initiation
- Assess clinical response (fever, hemodynamics, WBC) at 48-72 hours
- Obtain TDM if available to guide dose optimization
Days 2-7 (active treatment)
What you might notice
- Clinical improvement: defervescence, improving hemodynamics, decreasing WBC
- Negative blood cultures (typically by day 3-5 if effective)
- Possible rise in serum creatinine — nephrotoxicity often appears in first week
- Skin hyperpigmentation may begin to appear with prolonged IV therapy
What's normal
- Microbiological clearance should occur within 3-5 days if organism is susceptible
- Mild creatinine rise is common and requires close monitoring but not necessarily dose change
- Neurotoxic symptoms typically stabilize at a given dose
- Combination therapy should show synergistic effects by this point
What's next
- Continue treatment for total 7-14 days guided by infection type and clinical response
- Renal function monitoring at least every 48 hours
- De-escalate or stop polymyxin B as soon as clinically appropriate
- Assess source control and repeat imaging if needed
Week 2-4 (completion and recovery)
What you might notice
- Infection resolved — treatment typically completed at 7-14 days
- Renal function recovery begins after discontinuation (may take 1-4 weeks)
- Neurological symptoms resolve over days to weeks after stopping
- Skin hyperpigmentation gradually fades over weeks to months
What's normal
- Nephrotoxicity is usually reversible — creatinine should trend toward baseline after stopping
- Full renal recovery may take 2-4 weeks in some patients
- Neurotoxicity resolves completely in most patients after discontinuation
- Post-treatment surveillance for infection relapse is standard practice
What's next
- Complete any required follow-up cultures to confirm cure
- Monitor renal function until return to baseline
- Antimicrobial stewardship review for future infection prevention
- Address underlying risk factors for MDR infection (ICU stay, invasive devices)
Signs it's working
Treatment Response
- Improvement in the primary symptoms or condition being treated
- Positive changes in relevant lab values or clinical markers
- Consistent, stable response to Polymyxin B over time
- Reduction in symptom frequency or severity
General Well-being
- Improved energy levels and daily functioning
- Better quality of life related to the treated condition
- Manageable or absent side effects indicating good tolerance
- Positive feedback from healthcare provider during check-ups
Not seeing results? Common reasons
- Not at therapeutic dose yet—initial doses are for building tolerance, not maximum effect
- Insufficient time at target dose—most compounds need several weeks to show full benefits
- Inconsistent dosing schedule—regular, consistent use is crucial for optimal results
- Individual variation in response—genetics, metabolism, and other factors affect outcomes
- Underlying conditions or medications interfering with absorption or effectiveness
- Improper storage leading to degraded product—always verify proper storage conditions
Key research
Clinical trials
Tested in people
69 registered studies, 16 still enrolling.
By phase
A trial spanning two phases is counted in both, so these can sum above the total. Observational studies carry no phase.
What kind of research
About 7,472 people took part in the studies that actually administered Polymyxin B. Observational studies analyse the records of people already taking it — nobody was given anything for the study, so they are counted separately and cannot show cause and effect.
Most recent
EAA-Guided AN69-oXiris and PMX-HP Therapy in Septic Patients
Kyoung Moo Im
BV100-010
Bioversys S.A.S.
Safety, Pharmacokinetics and Efficacy of BV100 Plus Low Dose Polymyxin B Plus Ceftazidime/Avibactam, or Plus Cefiderocol in Patients With Pulmonary and Extrapulmonary Infections Due to Carbapenem-resistant Acinetobacter Baumannii-calcoaceticus Complex
BioVersys AG
Sources: ClinicalTrials.gov, the EU Clinical Trials Information System and ISRCTN, deduplicated so a study registered twice is counted once. A study is counted when Polymyxin B is named as an intervention; studies that only mention it in passing are not.
Questions
Frequently asked
Why is polymyxin B called a 'last resort' antibiotic?
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.
What is the difference between polymyxin B and colistin (polymyxin E)?
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.
How serious is the nephrotoxicity 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.
Can polymyxin B be used for Gram-positive infections?
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).
Is the polymyxin B in Neosporin the same as IV polymyxin B?
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 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.
Why was polymyxin B abandoned and then brought back?
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.
Further reading
History & related research
History · since 1947
The abandoned antibiotic that became the last hope against superbugs
Polymyxin B is an antibiotic discovered in 1947 from soil bacteria. It can kill dangerous gram-negative bacteria that resist almost all modern drugs.
Read the full history of Polymyxin BReady for the protocol?
Every dosing tier, administration route, timing note, and dose-adjustment rule for Polymyxin B, on one page.