Polymyxin B and Colistin

polymyxin B; colistin = polymyxin E (prodrug colistimethate sodium, CMS, Coly-Mycin M, Colomycin, Promixin)

Antimicrobial & antiviral

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Note on this profile. Polymyxin B and colistin are approved prescription antibiotics for severe, often resistant infections. This page explains the published science and modern dosing from consensus guidelines. These are toxic, narrow-margin drugs used under specialist supervision with kidney monitoring; they are not for self-directed use.

Summary

Class: Naturally occurring cyclic cationic lipopeptide antibiotics from Paenibacillus polymyxa; each has a fatty-acyl tail and a cyclic peptide ring
Mechanism: Their positive charge binds lipid A of lipopolysaccharide in the Gram-negative outer membrane, disrupting it and the inner membrane and killing the cell
Routes studied: Intravenous (systemic, last-line for resistant Gram-negatives), inhaled (cystic fibrosis), topical/ophthalmic, and gut decontamination (oral, non-absorbed)
Half-life: Colistin (active) ~several hours, longer with renal impairment; polymyxin B cleared largely non-renally
Storage: Hospital pharmacy product (CMS reconstituted for infusion)
Regulatory status: Approved antibiotics (US, EU, UK, AU, ZA and widely); reserved, specialist/last-line use

Doses are as reported in studies or by the community — never recommendations.

1What it is

Polymyxin B and colistin (polymyxin E) are old antibiotics from the bacterium Paenibacillus polymyxa. Each is a ring-shaped peptide carrying a fatty tail, which makes them lipopeptides. They were largely shelved decades ago because of kidney toxicity, but the rise of carbapenem-resistant Gram-negative "superbugs" has brought them back as last-line treatments when little else works. Colistin is usually given as an inactive prodrug, colistimethate sodium (CMS), which converts to active colistin in the body.

These are serious hospital antibiotics prescribed and dosed by specialists, not community self-use compounds. They appear here because they are important approved peptide antibiotics and are frequently discussed alongside the research antimicrobial peptides on this site.

2How it's thought to work

Outer-membrane attack. the positively charged peptide ring binds the negatively charged lipid A portion of lipopolysaccharide (LPS) in the Gram-negative outer membrane, displacing stabilising magnesium and calcium and breaking up the membrane.

Inner-membrane disruption. the drug then reaches and permeabilises the inner membrane, killing the cell.

Endotoxin binding. by binding lipid A (the toxic core of ) they can also neutralise some LPS activity.

Spectrum. active against many Gram-negative bacteria (including Pseudomonas, Acinetobacter, Klebsiella and other Enterobacterales); Gram-positives and some species (e.g. Proteus, Serratia) are intrinsically resistant.

Cyclic lipopeptides that bind lipid A in the outer membrane of Gram-negative bacteria and break it open. Kept in reserve because of kidney and nerve toxicity.Schematic — not to scale

3What the research shows

Resistant Gram-negative infections

Polymyxins are established therapy for carbapenem-resistant Gram-negative infections where few options exist; efficacy is accepted but outcomes are limited by toxicity and by difficulty achieving adequate drug levels. Modern use is governed by the 2019 international consensus guidelines (Tsuji 2019, Pharmacotherapy), endorsed by ACCP, IDSA, SCCM, SIDP and ISAP, which set the loading/maintenance doses above and plasma-exposure targets (colistin average steady-state ~2 mg/L; AUC ~50 mg·h/L). [1]

Nephrotoxicity

Acute kidney injury is common and dose-related; the guidelines note that exposures above target raise AKI risk and, where both drugs are available, prefer polymyxin B for systemic use because its pharmacokinetics are more predictable and it is less nephrotoxic, reserving colistin for lower urinary-tract infection (where its renal excretion helps). Neurotoxicity (paraesthesia, rarely neuromuscular blockade) also occurs.

Graded A/B

Inhaled colistin in cystic fibrosis

Nebulised colistin is used to manage chronic Pseudomonas airway infection in cystic fibrosis.

Topical/ophthalmic and gut decontamination

Polymyxin B features in approved topical/eye combinations (see Gramicidin); oral non-absorbed polymyxins are used in selective digestive decontamination research.

4Reported side effects and interactions

Literature-reported

dose-related nephrotoxicity (acute kidney injury) is the principal limitation; neurotoxicity (circumoral/limb paraesthesia, dizziness, rarely neuromuscular blockade and apnoea) occurs; infusion reactions and, for inhaled colistin, bronchospasm. Older toxicity estimates were worsened by confusing dosing units.

Community-reported

Community use: essentially none documented. These are specialist IV antibiotics, not self-use peptides.

Theoretical. emergence of polymyxin resistance (including transferable mcr genes) is a major public-health concern.

Interactions. additive kidney damage with other nephrotoxins (aminoglycosides, vancomycin, contrast, NSAIDs); additive neuromuscular blockade with anaesthetic blockers.

Markers researchers commonly monitor

These follow standard prescribing and the consensus guidelines (clinician-directed, inpatient):

Marker	Why it's watched
Serum creatinine / eGFR	the key safety marker; AKI is common and dosing is renally adjusted (colistin; polymyxin B maintenance is generally not).
Urine output	tracks evolving kidney injury.
Therapeutic drug monitoring (where available)	plasma colistin targeting ~2 mg/L average steady state per the guidelines.
Signs of neurotoxicity	paraesthesia, weakness; clinical, not a lab test.
Culture and susceptibility (MIC)	guides whether a polymyxin is appropriate and at what target.

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Hospital pharmacy products: colistimethate sodium is for IV infusion or nebulisation; polymyxin B is supplied for IV use. Dosing uses specific units (colistin base activity vs IU vs CMS mg) and unit confusion has historically caused dosing errors — a prescriber/pharmacy responsibility, not a self-reconstitution task. No calculator link applies.

6Commonly studied alongside

Carbapenems and newer β-lactam/β-lactamase-inhibitor agents (combination therapy for resistant Gram-negatives), Gramicidin and neomycin (in topical combinations), aminoglycosides (with caution, shared toxicity).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (colistimethate — Coly-Mycin M; polymyxin B); reserved for serious infections
European Union	Authorised (colistin/CMS; polymyxin B); EMA has issued dosing guidance
United Kingdom	MHRA-licensed (Colomycin, Promixin; polymyxin B)
Australia	TGA-approved
South Africa	SAHPRA-registered
Sport	Not listed by WADA; not a performance substance

8Open questions

Can dosing and therapeutic drug monitoring be optimised to keep efficacy while cutting kidney injury?
How fast will transferable polymyxin resistance (mcr) spread, and what replaces these last-line drugs?
Is combination therapy better than polymyxin monotherapy for the worst resistant infections?

9References

1Tsuji BT et al. (2019). International Consensus Guidelines for the Optimal Use of the Polymyxins. Pharmacotherapy. PubMed
2Nation RL et al. (2015). Framework for optimisation of the clinical use of colistin and polymyxin B. Lancet Infect Dis. PubMed · DOI
3Falagas ME, Kasiakou SK (2005). Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin Infect Dis. PubMed · DOI
4Velkov T et al. (2010). Structure–activity relationships of polymyxin antibiotics. J Med Chem. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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