Polymyxin B
The older polymyxin, given as the active drug rather than a prodrug, with a boxed warning on both kidneys and nerves
Polymyxin B breaks open the outer membrane of gram-negative bacteria. Unlike colistin it is given as the active antibiotic, not a prodrug. Its label carries a boxed warning for kidney and nerve toxicity, and a separate line of research uses it on a filter to pull endotoxin out of blood.
What is it?
Polymyxin B increases the permeability of the bacterial outer membrane by displacing the cations that hold lipopolysaccharide together, and the cell dies. Gram-positive bacteria, fungi and gram-negative cocci are unaffected. Unlike colistin, it is given as the active drug rather than a prodrug.
Its label is from another era. The boxed warning limits intramuscular or intrathecal use to hospitalised patients under constant supervision, requires dose reduction in kidney impairment, and warns that combining it with muscle relaxants can cause respiratory paralysis. Intravenous dosing is 15,000 to 25,000 units/kg a day with normal kidneys, given as a drip or every 12 hours, never above 25,000 units/kg; a 2021 study measured a half-life of about 4.1 hours.
Kidney injury is the constant companion. In one 96-patient study half the patients developed it, yet reaching the target drug exposure improved cure without adding kidney risk, which tracked how sick and inflamed patients were and whether they also received vancomycin. Pooled across 96 studies, higher doses did not lower mortality but did harm the kidneys more. In a large Chinese trial, a higher dose was no better at 14 days than a lower one. Against colistin sulfate in one cohort, it cured as often but caused more severe kidney injury.
Delivering it to the lungs avoids some of that. Inhaled polymyxin B alone worked as well as inhaled plus intravenous for resistant pneumonia, with less kidney toxicity, and nebulised treatment cleared the organism in about seven in ten patients in an uncontrolled series.
Its most-studied recent use is not as an antibiotic: blood passed over a polymyxin B filter to remove endotoxin in septic shock. That failed a large 2018 trial, showed probable benefit in a smaller 2026 one, and a meta-analysis of 13 trials suggested lower mortality in less severe sepsis while calling the evidence inconclusive. Filters clot in about a third of prolonged sessions, without apparent harm.
Mechanism of Action
Polymyxin B disrupts the outer membrane of gram-negative bacteria and binds their endotoxin, the basis of both its antibiotic and haemoperfusion uses.
Outer membrane
Displaces the cations that bridge lipopolysaccharide, making the membrane permeable (label).
Endotoxin binding
Immobilised on a filter, it binds circulating endotoxin during haemoperfusion.
Kidney toxicity
Dose-limited by kidney injury; the label requires reduction in kidney impairment.
Published Research
These are the trials in people, read from their PubMed abstracts, with dosing and safety from the polymyxin B sulfate injection label read on October 1, 2026.
The large endotoxin-removal trial was negative
In EUPHRATES, 450 patients with septic shock and high endotoxin activity were randomised to two polymyxin B haemoperfusion treatments or sham. Death at 28 days was 37.7% against 34.5%, no significant difference, and the result held in the sicker subgroup.
A smaller Bayesian trial found a probable benefit
Tigris enrolled 157 patients with endotoxic septic shock across 19 US hospitals after screening 14,890. Death at 28 days was 39% with polymyxin B haemoperfusion against 45% with standard care, a 95.3% posterior probability of benefit, rising to 99.4% at 90 days.
How often kidney injury happens
In a double-blind trial testing whether melatonin could prevent kidney injury in 88 patients receiving intravenous polymyxin B, melatonin made no difference. Acute kidney injury occurred in 52.3% of patients overall.
PMB-CROS: two doses with drug monitoring
In 311 patients with carbapenem-resistant sepsis, a higher and a lower intravenous dose gave similar 14-day response (62.5% against 59.7%); reaching the exposure target tracked with kidney injury, not cure.
Inhaled alone against inhaled plus intravenous
In 78 patients with carbapenem-resistant Gram-negative pneumonia, inhaled polymyxin B alone and inhaled plus intravenous gave similar cure and mortality, with less kidney toxicity on inhaled alone and higher drug levels in lung lining fluid.
Nebulised for resistant pneumonia
In 91 patients with carbapenem-resistant Gram-negative pneumonia given nebulised polymyxin B for a median 9 days, mostly with intravenous polymyxin B too, total eradication was 72.4%. There was no control group.
Exposure, cure and kidney injury
In 96 patients, half developed kidney injury; reaching the target exposure (AUC 50 to 100 mg·h/L) improved clinical success (68.0% against 45.8%) without raising kidney risk, which tracked septic shock, inflammation and vancomycin.
Clotting during prolonged haemoperfusion
In 82 patients with septic shock on prolonged polymyxin B haemoperfusion, a third had the circuit clot and stop early, without worse 28-day mortality; low albumin predicted clotting.
Against colistin sulfate
In 163 critically ill patients with carbapenem-resistant infections, polymyxin B and colistin sulfate had similar cure and mortality, but severe kidney injury was more frequent on polymyxin B.
96 studies, 9,716 patients
Across 96 studies, high and low daily doses of polymyxin B had similar overall mortality (33.6% against 35.4%); mortality was highest with Pseudomonas aeruginosa and with monotherapy, and kidney dysfunction was more common at high doses.
Haemoperfusion meta-analysis
Across 13 randomised trials of 1,163 patients, polymyxin B haemoperfusion was associated with lower mortality (relative risk 0.68), mainly in less severe sepsis, but trial sequential analysis found the evidence inconclusive.
Dosing Data
Polymyxin B is infused intravenously at 15,000 to 25,000 units/kg a day with normal kidneys, as a continuous drip or every 12 hours; intramuscular and intrathecal use are restricted.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the polymyxin B sulfate injection label (SPL version 13, effective June 22, 2026), whose boxed warning covers most of this.
Contraindications & Cautions
From the label.
Legal Status
An approved antibiotic of long standing.
Frequently Asked Questions
?How does polymyxin B differ from colistin?
Colistin is polymyxin E and is given as an inactive prodrug, colistimethate. Polymyxin B is given as the active drug itself. Both work the same way on the bacterial outer membrane.
?What is the dose?
The label gives 15,000 to 25,000 units/kg a day intravenously with normal kidneys, reduced for kidney impairment.
?How toxic is it?
Its label carries a boxed warning for kidney and nerve toxicity. In a 2023 trial, 52.3% of patients given it intravenously developed acute kidney injury.
?What is polymyxin B haemoperfusion?
Passing blood over a polymyxin B filter to remove endotoxin. EUPHRATES (450 patients) found no survival benefit; Tigris (157) reported a 95.3% probability of benefit.
References
- [fda-pi] Polymyxin B sulfate for injection prescribing information, boxed warning, Indications, Dosage and Administration and Precautions (DailyMed SPL version 13, effective June 22, 2026; read October 1, 2026).
- [pubmed] Dellinger RP, et al. "Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial." JAMA, 2018;320(14):1455-1463. PMID: 30304428.
- [pubmed] Neyra JA, et al. "Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial." Lancet Respir Med, 2026;14(5):443-452. PMID: 41887242.
- [pubmed] Rigatto MH, et al. "Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial." Clin Microbiol Infect, 2023;29(5):623-628. PMID: 36586514.
- [pubmed] Zavascki AP, et al. "Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review." J Antimicrob Chemother, 2007;60(6):1206-15. PMID: 17878146.
- [pubmed] Crass RL, et al. "Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis." Antimicrob Agents Chemother, 2021;65(10):e0079221. PMID: 34252297.
- [pubmed] Cheng Y, et al. "Inhaled alone versus inhaled plus intravenous polymyxin B for the treatment of pneumonia due to carbapenem-resistant gram-negative bacteria: A prospective randomized controlled trial." Int J Antimicrob Agents, 2025;65(5):107483. PMID: 40023452.
- [clinical-trial] Liu S, et al. "Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial." Crit Care, 2023;27(1):232. PMID: 37312218.
- [pubmed] Zhu M, et al. "Safety and Efficacy of Nebulized Inhalation of Polymyxin B Sulfate for Carbapenem-Resistant Gram-Negative Bacterial Pneumonia: A Multi-Center, Prospective, Observational Study." Infect Drug Resist, 2026;19:594579. PMID: 42158358.
- [pubmed] Luo X, et al. "Host inflammation drives low-exposure nephrotoxicity in critically ill patients receiving polymyxin B: A prospective study." Int J Antimicrob Agents, 2026;67(11):107980. PMID: 42660470.
- [pubmed] Zhao YC, et al. "Factors affecting the effectiveness and safety of polymyxin B in the treatment of Gram-negative bacterial infections: A meta-analysis of 96 articles." Int J Antimicrob Agents, 2024;64(3):107262. PMID: 38945178.
- [pubmed] Li X, et al. "Effectiveness of polymyxin B-immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis." J Crit Care, 2021;63:187-195. PMID: 33012579.
- [pubmed] Miyamoto K, et al. "Incidence and Clinical Outcomes of Circuit Clotting During Prolonged Polymyxin B Hemoperfusion in Patients With Septic Shock: A Post Hoc Analysis of a Prospective Cohort Study." Ther Apher Dial, 2026. PMID: 42608712.
- [pubmed] Xu Y, et al. "Comparative efficacy and safety of colistin sulfate versus polymyxin B in critically ill patients with carbapenem-resistant gram-negative infections: a pilot inverse probability of treatment weighting-based retrospective cohort study." BMC Infect Dis, 2026;26(1). PMID: 42337470.
- [fda-pi] Polymyxin B for injection USP US prescribing information (Hikma; DailyMed set 18daf0d1, effective April 28, 2022), Dosage and Administration; read through openFDA October 6, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; the polymyxin B label from DailyMed (Hikma, set 18daf0d1, effective April 28, 2022) through openFDA, read October 6, 2026.
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