Colistin
A 1950s antibiotic brought back for bacteria that nothing else kills, with the kidney toxicity that retired it
Colistin, polymyxin E, is given as the inactive prodrug colistimethate sodium. It punches holes in the outer membrane of gram-negative bacteria. Abandoned in the 1970s for safer drugs, it returned as resistance spread, and newer antibiotics are now measured against it.
What is it?
Colistin is a cyclic lipopeptide. Its positively charged ring displaces the magnesium and calcium that hold the outer membrane of gram-negative bacteria together, and the cell leaks. It is given as colistimethate sodium, inactive until it converts to colistin in the body.
Coly-Mycin M Parenteral was approved in the United States in 1970 (NDA 050108). The labels set 2.5 to 5 mg/kg a day of colistin base in two to four doses for adults and children with normal kidneys, dosed by ideal body weight in obesity, never more than 5 mg/kg a day, with lower doses as kidney function falls and a serum half-life of 2 to 3 hours. Each vial carries the equivalent of 150 mg of colistin base.
The label's warnings are the reason it was shelved in the first place: dose-dependent kidney damage, and nerve effects including numbness around the mouth, tingling, dizziness and slurred speech, which it says is reason enough not to drive while being treated. Carbapenem resistance brought it back as a last resort.
The trials of the past decade have mostly used colistin as the comparator: adding meropenem did not improve its results, a newer drug beat it on kidney harm, and inhaled colistimethate for bronchiectasis worked in one of two parallel trials and not the other. Pooled across 26 studies, combinations improved bacterial clearance slightly without lowering mortality; observational data favour cefiderocol over colistin-based regimens for resistant Acinetobacter.
Partners still matter. With colistin, a higher sulbactam dose was linked to lower mortality in Acinetobacter pneumonia, and a small double-blind trial reported better cure with doxycycline added. Against its close relative polymyxin B, colistin sulfate worked as well and caused less severe kidney injury in one Chinese cohort.
Mechanism of Action
Colistin (polymyxin E) breaks open the outer membrane of gram-negative bacteria by displacing the cations that hold it together.
Cation displacement
Its positively charged ring displaces magnesium and calcium from lipopolysaccharide.
Membrane leak
The outer and inner membranes become permeable and the cell dies.
Prodrug
Given as colistimethate sodium, which converts to active colistin in the body.
Published Research
These are the trials in people, read from their PubMed abstracts, with the label figures taken from the Coly-Mycin M SPL read on October 1, 2026.
Adding meropenem did not help
In a randomised trial in severe infections from carbapenem-resistant gram-negative bacteria, clinical failure at 14 days was 79% with colistin alone and 73% with colistin plus meropenem, not a significant difference.
Beaten on kidney harm, not on deaths
In the ATTACK trial, sulbactam-durlobactam was non-inferior to colistin for 28-day deaths from carbapenem-resistant Acinetobacter infections. Kidney toxicity was much lower with the newer drug: 13% of 91 patients against 38% of 85 on colistin.
Inhaled, it worked in one trial of two
PROMIS-I and PROMIS-II tested 12 months of inhaled colistimethate against placebo in bronchiectasis with Pseudomonas infection. PROMIS-I suggested a clinically important benefit; PROMIS-II, cut short during the COVID-19 pandemic, did not reproduce it, with an exacerbation rate ratio of 1.00.
Kidney harm against a newer antibiotic
In RESTORE-IMI 1, in 31 patients with imipenem-resistant infections, favourable response was 71% with imipenem/relebactam and 70% with colistin plus imipenem; kidney toxicity emerged in 10% and 56%.
With doxycycline: a small double-blind trial
In 46 patients with multidrug-resistant Gram-negative infections, colistin plus doxycycline gave higher clinical cure (87.0% against 46.7%) and lower mortality (69.6% against 86.7%) than the comparator regimen; the trial was small.
With sulbactam: 9 g against 12 g
In 138 patients with carbapenem-resistant Acinetobacter pneumonia on colistin plus sulbactam, 12 g/day of sulbactam was linked to lower adjusted mortality (hazard ratio 0.54) and better day-7 microbiological cure than 9 g/day.
Colistin sulfate against polymyxin B
In 163 critically ill patients with carbapenem-resistant infections, colistin sulfate and polymyxin B had similar cure and mortality, but severe kidney injury was more frequent on polymyxin B.
Combination or monotherapy
Across 26 studies of carbapenem-resistant infections, colistin combinations raised microbial eradication slightly (relative risk 1.07), mainly for Acinetobacter baumannii, but did not lower 28-day mortality.
Against cefiderocol for resistant Acinetobacter
In six observational studies, cefiderocol-based regimens had lower all-cause (relative risk 0.71) and 30-day mortality than colistin-based regimens for carbapenem-resistant Acinetobacter.
Klebsiella bloodstream infection
Pooling six observational studies, colistin monotherapy did not differ significantly from tigecycline or carbapenem monotherapy for Klebsiella pneumoniae bloodstream infection; no randomised trials existed.
Dosing Data
Colistimethate is given intravenously or intramuscularly in two to four daily doses, dosed as colistin base by ideal body weight and reduced in kidney impairment.
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 Coly-Mycin M Parenteral label (SPL version 27, effective June 8, 2026) and the trials above.
Contraindications & Cautions
From the label and the dosing ceiling it sets.
Legal Status
An approved antibiotic, used where little else works.
Frequently Asked Questions
?What is colistin used for?
Infections from gram-negative bacteria that resist other antibiotics, particularly Pseudomonas aeruginosa. Its label lists treatment of acute or chronic infections due to sensitive gram-negative bacilli.
?Why is it considered a last resort?
Because of its toxicity. The label warns of dose-dependent kidney damage and nerve effects, and in recent trials kidney toxicity affected 38% and 56% of patients given it.
?Is colistin the same as polymyxin E?
Yes. It is given as colistimethate sodium, an inactive prodrug that converts to colistin in the body.
?How long does it last in the blood?
The Coly-Mycin M label reports serum concentrations declining with a half-life of 2 to 3 hours after intravenous or intramuscular dosing, in adults and children including premature infants.
?Is colistin or polymyxin B safer for the kidneys?
In one Chinese cohort of 163 critically ill patients, cure and mortality were similar but severe kidney injury was more frequent on polymyxin B than on colistin sulfate; both carry kidney warnings.
?Does adding a second antibiotic help?
Pooled studies show slightly better bacterial clearance with combinations but no lower mortality; partner choice and dose, such as higher-dose sulbactam for Acinetobacter, may matter more.
References
- [fda-pi] Coly-Mycin M Parenteral (colistimethate sodium) prescribing information, Dosage and Administration, Warnings and Clinical Pharmacology (DailyMed SPL version 27, effective June 8, 2026; read October 1, 2026).
- [pubmed] Paul M, et al. "Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial." Lancet Infect Dis, 2018;18(4):391-400. PMID: 29456043.
- [pubmed] Kaye KS, et al. "Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK)." Lancet Infect Dis, 2023;23(9):1072-1084. PMID: 37182534.
- [pubmed] Haworth CS, et al. "Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: results of PROMIS-I and PROMIS-II, two randomised, double-blind, placebo-controlled phase 3 trials assessing safety and efficacy over 12 months." Lancet Respir Med, 2024;12(10):787-798. PMID: 39270696.
- [pubmed] Motsch J, et al. "RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections." Clin Infect Dis, 2020;70(9):1799-1808. PMID: 31400759.
- [pubmed] Nation RL, et al. "Colistin in the 21st century." Curr Opin Infect Dis, 2009;22(6):535-43. PMID: 19797945.
- [clinical-trial] Abaft S, et al. "Efficacy and safety of colistin-doxycycline combination therapy in multi-drug resistance Gram-negative infections: a double-blind randomized controlled trial." Infection, 2026;54(1):487-502. PMID: 41264225.
- [pubmed] Yang T, et al. "Colistin-based combination therapy versus monotherapy for carbapenem-resistant gram-negative bacterial infections: a systematic review and meta-analysis." Front Cell Infect Microbiol, 2025;15:1729919. PMID: 41602103.
- [clinical-trial] Ungthammakhun C, et al. "Effect of colistin combined with sulbactam: 9 g versus 12 g per day on mortality in the treatment of carbapenems resistant Acinetobacter baumannii pneumonia: A randomized controlled trial." Int J Infect Dis, 2024;149:107267. PMID: 39423948.
- [pubmed] Zhan Y, et al. "Comparison of cefiderocol and colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review with meta-analysis and trial sequential analysis." BMC Infect Dis, 2024;24(1):967. PMID: 39271977.
- [pubmed] Wang T, et al. "Colistin monotherapy or combination for the treatment of bloodstream infection caused by Klebsiella pneumoniae: a systematic review and meta-analysis." BMC Infect Dis, 2024;24(1):161. PMID: 38317132.
- [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] Colistimethate for injection USP US prescribing information (Xellia; DailyMed set 13dc3525, effective August 29, 2024), Dosage and Administration; read through openFDA October 6, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; the Coly-Mycin M label read October 1, 2026, and the generic colistimethate label through openFDA (set 13dc3525) October 6, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.