Why is colistin considered a last-resort drug?

It was largely abandoned decades ago because of toxicity, then revived as resistance spread. It is reserved for resistant infections because of significant nephrotoxicity and neurotoxicity.

What are colistin's main side effects?

The two dose-limiting toxicities are kidney injury (nephrotoxicity), which is common and exposure-related, and nervous-system effects (neurotoxicity) such as paresthesias, dizziness, and, rarely, neuromuscular blockade. Careful dosing and renal monitoring are essential.

Is colistin approved by regulators?

Yes - colistimethate sodium is approved in the US and many other countries - but it is used selectively under specialist supervision because of its toxicity profile.

Should colistin be combined with other antibiotics?

Not routinely. A randomized trial found that adding meropenem to colistin did not improve outcomes for carbapenem-resistant Gram-negative infections, so any combination is a specialist, case-by-case decision.

EMA-approvedaka Polymyxin E

Colistin — Complete Research Guide (2026)

Last updated 2026-06-30

TL;DR

Colistin (also known as Polymyxin E) is a peptide catalogued under Cyclic & Antimicrobial (Polymyxin). It is described as: LPS/outer membrane disruption. Documented context: MDR Gram-negative infections. Neutral reference entry; EU status: EU-approved prescription medicine.

What is Colistin?

Colistin (polymyxin E), administered as the prodrug colistimethate sodium, is a cyclic lipopeptide/polymyxin antibiotic first introduced in the 1950s and revived as a last-resort agent against multidrug-resistant Gram-negative infections - including Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales.

It is a physician-prescribed, hospital-administered drug (not a supplement); colistimethate is approved in the US and many other countries, but its use is reserved for resistant organisms because of significant toxicity.

Evidence is human and clinical, spanning an international consensus guideline, a randomized controlled trial, and systematic reviews, alongside older observational data.

How does Colistin work?

Colistin is a cationic polypeptide that binds lipid A of lipopolysaccharide in the Gram-negative outer membrane, displacing divalent cations and disrupting membrane integrity, which causes leakage of cell contents and bacterial death.

This membrane-targeting action gives it activity against many Gram-negative bacteria that have become resistant to other antibiotic classes.

What does the research say about Colistin?

Colistin re-emerged as a critical last-line option when few or no other agents remain active against multidrug-resistant Gram-negative bacteria. ^[3]
An international, multi-society consensus guideline provides optimized, exposure-based dosing to improve efficacy while limiting toxicity. ^[1]
In a randomized trial for severe carbapenem-resistant Gram-negative infections, adding meropenem to colistin did not improve outcomes over colistin alone, informing rational last-resort use. ^[2]

Clinical research & studies

The references below are the primary sources cited throughout this guide. Each links directly to PubMed or the regulator. Where evidence is preclinical (animal or in-vitro), that is stated rather than implied.

[1] International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP) — Tsuji BT et al., Pharmacotherapy 2019. (International consensus guideline)
[2] Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial — Paul M et al., Lancet Infectious Diseases 2018. (Open-label randomized controlled trial)
[3] Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections — Falagas ME et al., Clinical Infectious Diseases 2005. (Narrative review)
[4] Colistin in the 21st century — Nation RL et al., Current Opinion in Infectious Diseases 2009. (Narrative review)
[5] Toxicity of polymyxins: a systematic review of the evidence from old and recent studies — Falagas ME et al., Critical Care 2006. (Systematic review)
[6] Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence — Falagas ME et al., International Journal of Antimicrobial Agents 2007. (Systematic review)

Dosing context

This is not medical advice or a usage recommendation. Dosing figures are reported research context only, cited from the published literature.

For context only: colistin (as colistimethate sodium) is given intravenously in hospital with a weight- and renal-function-based loading dose followed by maintenance dosing, and is sometimes given by inhalation or intrathecally/intraventricularly for specific infections.

Dosing is complex and specialist-managed with drug-level/renal monitoring; nothing here is dosing advice and it is never self-administered.

Side effects & safety profile

Colistin's two major dose-limiting toxicities are nephrotoxicity (acute kidney injury, often reversible) and neurotoxicity (paresthesias, dizziness, and rarely neuromuscular blockade/apnea), both well documented in systematic reviews.

Nephrotoxicity is common and exposure-related, so it is reserved for resistant infections, dosed carefully, and used with close renal-function monitoring, ideally with therapeutic drug monitoring where available.

It must only be used under specialist supervision in hospital; risk increases with higher doses, longer courses, pre-existing renal impairment, and concurrent nephrotoxins.

Stacking & combinations

It is sometimes used in combination regimens for resistant organisms, but randomized evidence does not support routinely adding a carbapenem to colistin, and any combination is a specialist decision.

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Frequently asked questions

It is a last-resort antibiotic for serious infections caused by multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales, when other options are unavailable.

References

[1] International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP) — Tsuji BT et al., Pharmacotherapy 2019. PMID: 30710469. View sourceStudy: International consensus guidelineProvides exposure-based colistin dosing and monitoring recommendations to balance efficacy against nephrotoxicity.
[2] Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial — Paul M et al., Lancet Infectious Diseases 2018. PMID: 29456043. View sourceStudy: Open-label randomized controlled trialAdding meropenem to colistin did not improve clinical outcomes versus colistin monotherapy for carbapenem-resistant Gram-negative infections.
[3] Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections — Falagas ME et al., Clinical Infectious Diseases 2005. PMID: 15825037. View sourceStudy: Narrative reviewDocuments the return of colistin as a last-resort option amid rising multidrug-resistant Gram-negative infections.
[4] Colistin in the 21st century — Nation RL et al., Current Opinion in Infectious Diseases 2009. PMID: 19797945. View sourceStudy: Narrative reviewReviews modern pharmacology, dosing challenges and toxicity of colistin/colistimethate in the resistance era.
[5] Toxicity of polymyxins: a systematic review of the evidence from old and recent studies — Falagas ME et al., Critical Care 2006. PMID: 16507149. View sourceStudy: Systematic reviewSynthesizes evidence that nephrotoxicity and neurotoxicity are the principal, dose-related polymyxin toxicities.
[6] Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence — Falagas ME et al., International Journal of Antimicrobial Agents 2007. PMID: 17126534. View sourceStudy: Systematic reviewReviews intraventricular/intrathecal polymyxin use for resistant Gram-negative CNS infections and its safety signals.

This article is for educational and research purposes only. Peptides discussed here are not approved for human consumption by the FDA, EMA, or equivalent regulators outside of specific clinical contexts. Always consult a licensed medical professional before any therapeutic use.