Peptide profile · Immune
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 & reviewed by Michael Carroll · Research, Peptide Initiative
Typical dose
Maintenance 1.25-1.5 mg/kg (12,500-15,000 IU/kg) every 12 hours, infused over 1 hour
Half-life
Terminal half-life: 9-11.5 hours in patients with normal renal function; does not require renal dose adjustment (unlike colistimethate); achieves steady-state within 1-2 days with loading dose
Bioavailability
IV: 100% (direct administration); oral: negligible (not absorbed from GI tract — used topically in the gut for selective decontamination); inhaled: local pulmonary concentrations achieved with systemic absorption variable; topical: minimal systemic absorption
Molecular weight
1,203.5 g/mol (free base); ~1,385 g/mol (sulfate salt)
Evidence level
Strong human trials
01 · Compound profile
Scientific & efficacy data
Molecular formula
C₅₆H₉₈N₁₆O₁₃ (polymyxin B₁ free base)
Primary benefits
This antibiotic kills dangerous bacteria that have learned to resist almost every other treatment, often serving as the last line of defense.
It grabs onto harmful toxins released by bacteria during serious infections, which may help calm the body's dangerous overreaction.
When applied to skin as a cream or ointment, it prevents bacteria from infecting cuts, scrapes, and burns.
Colistin Industries / Hospira Pharmaceuticals
Amino acid sequence
Dab-Dab-Dab-Phe-Dab-Phe-Dab-Asp-Dab-Dab (cyclic with fatty acid)02 · Dosing
How much do I take?
Maintenance 1.25-1.5 mg/kg (12,500-15,000 IU/kg) every 12 hours, infused over 1 hour · every 12 hours
Intramuscular: An injection into a muscle, usually the thigh, shoulder, or buttock.
Bioavailability High — well absorbed into the bloodstream from the muscle.
Best time to take
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.
With food?
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.
If stacking
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.
＋ Increase if
- +You've tolerated the current dose for the recommended period without significant side effects
- +Therapeutic goals haven't been met at the current dose level
- +Your healthcare provider recommends dose escalation based on your response
- +Lab work or clinical assessments support a higher dose
－ Decrease if
- −Side effects are bothersome or impacting daily life despite management strategies
- −You experience any signs of an adverse reaction
- −Lab results indicate the need for dose reduction
- −Your healthcare provider recommends a lower dose based on your response
✓ Signs of right dose
- ✓Therapeutic goals being met with minimal side effects
- ✓Stable and consistent response to treatment
- ✓Lab values or clinical markers trending in the right direction
- ✓Good tolerance with manageable or absent side effects
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03 · 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.
04 · Administration
How do I use it?
Intravenous infusion (primary systemic route) · Intrathecal / intraventricular injection (CNS infections)
Reconstitution — what you need
Example
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.
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
Technique
- 01Wash your hands thoroughly with soap and water before handling supplies
- 02Clean the injection site with an alcohol swab and let it air dry completely
- 03Pinch a fold of skin at the chosen injection site
- 04Insert the needle at a 45-90 degree angle (depending on needle length and body composition)
- 05Inject the medication slowly and steadily over 5-10 seconds
- 06Release the skin fold and remove the needle, applying gentle pressure with a clean swab
- 07Rotate injection sites to prevent tissue irritation or lipodystrophy
- 08Dispose of the needle safely in a sharps container—never recap or reuse needles
Storage · before reconstitution
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.
Storage · after reconstitution
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.
Signs of degradation
Sample daily schedule
05 · Safety
Is it safe?
4 common side effects · 2 serious
Polymyxin B carries significant nephrotoxicity risk (acute tubular necrosis) and neurotoxicity risk (peripheral neuropathy, neurological effects) requiring strict monitoring. Serum concentrations >5 mg/L associated with increased renal dysfunction; dosing adjusted for creatinine clearance to minimize accumulation. IV or intramuscular use only; intrathecal administration reserved for meningitis with careful dosing. Bacterial resistance monitoring essential as polymyxins remain reserved antibiotics.
Clinical pharmacokinetic studies document polymyxin B mechanism through lipopolysaccharide binding (LPS) neutralization assays. Renal safety monitoring via creatinine clearance and cystatin C shows dose-dependent decline in GFR. Neurotoxicity correlates with serum levels >5 mg/L; electromyography studies show reversible neuromuscular junction effects. Meningitis studies show CSF penetration adequate for bacterial killing despite narrow therapeutic window.
Common side effects · experienced by some users
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
- ✓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.
- ✓Rifampicin (strong synergy against A. baumannii — rifampicin inhibits RNA polymerase after polymyxin permeabilizes the outer membrane barrier) — May be used together under medical guidance.
- ✓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
- !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.
- !Vancomycin at full doses — additive nephrotoxicity; if combination needed, monitor renal function daily — Use with caution—discuss with your healthcare provider.
- !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
- ✓Multivitamins — Generally safe to take alongside Polymyxin B. Space doses apart if taking oral formulations to ensure optimal absorption.
- ✓Electrolyte supplements — Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
06 · 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)
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.
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
Signs it's working · 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
07 · 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.
08 · 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 B