peptidechats
Research information only. Not medical advice. 18+ only. Not FDA-approved for human therapeutic use.

Colistin

Also known as: polymyxin E, colistimethate sodium, CMS, colistin sulfate, colimycin, colistin methanesulfonate, colistin sulfomethate

Cyclic lipopeptide antibiotic; polymyxin-class; last-resort gram-negative antimicrobial

Research chemicalLast updated: October 10, 2026Based on 4 peer-reviewed studiesPreclinical data only — no human trials
Ask about Colistin in chat →

What it is

Colistin is a last-resort antibiotic peptide used in hospitals to treat infections caused by bacteria that have become resistant to nearly every other antibiotic available. It fell out of use for decades due to kidney toxicity but was brought back as antibiotic resistance became a global crisis. FDA-approved for systemic injection and inhaled use.

The scientific side

colistin (polymyxin E) is a cyclic lipopeptide antibiotic that exerts its antibacterial activity primarily through disruption of the bacterial cell membrane, with a mechanism distinct from most other antibiotic classes. Colistin consists of a cyclic heptapeptide ring with a tripeptide side chain and a fatty acid tail; at physiological pH it carries a strong net positive charge due to five diaminobutyric acid (DAB) residues. This cationic charge allows colistin to competitively displace divalent cations (calcium and magnesium) that stabilize the lipopolysaccharide (LPS) molecules in the outer membrane of gram-negative bacteria. This destabilizes and disrupts the outer membrane, creating pores through which the drug enters. According to PMID 33821795, colistin does not kill solely by outer membrane disruption; rather, it translocates to the cytoplasmic (inner) membrane where it also targets LPS that has been trafficked there. This inner-membrane LPS targeting is the principal bactericidal event — gram-negative bacteria with MCR-1-mediated phosphoethanolamine modification of LPS in the inner membrane (rather than only the outer membrane) resist colistin killing. The result of colistin's membrane activity is leakage of intracellular contents, dissipation of the transmembrane potential, and rapid cell death. Colistin is bactericidal and concentration-dependent, meaning its killing efficacy is most strongly predicted by the ratio of the area-under-the-concentration-time-curve (AUC) to minimum inhibitory concentration (AUC/MIC). It has narrow-spectrum activity focused on gram-negative organisms including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae — the most clinically problematic carbapenem-resistant pathogens (PMIDs: 32284036, 28550595, 24794735). Resistance mechanisms include modification of LPS via addition of positively charged moieties (phosphoethanolamine or 4-aminoarabinose) that reduce electrostatic attraction of the cationic colistin molecule; these can be chromosomally encoded (pmrA/B, mgrB, phoPQ regulatory mutations) or plasmid-mediated (MCR-1 through MCR-9 genes), enabling horizontal gene transfer. Notably, PMID 38301486 demonstrated that bacteriophages can carry and disseminate colistin resistance genes among A. baumannii strains, representing an additional resistance dissemination pathway.

Class: Cyclic lipopeptide antibiotic; polymyxin-class; last-resort gram-negative antimicrobial

Administration & storage

Administration
Intravenous infusion (IV) — standard route for systemic MDR gram-negative infections in ICUIntramuscular injection (IM) — historical use; less common than IV in current practiceInhalation via nebulizer — for respiratory tract infectionscystic fibrosisand VAP adjunct therapyIntrathecal/intraventricular — case reports for MDR gram-negative meningitis/ventriculitis (off-label)
Storage
Unreconstituted CMS powder: store at controlled room temperature (15–30°C). Reconstituted solutions: use within 24 hours if refrigerated (2–8°C). Do not freeze reconstituted solutions. Inhaled solutions: prepare immediately before administration.
Cautions
Nephrotoxicity: most common and serious dose-limiting toxicity. Acute kidney injury occurs in 14–61% of patients depending on dosing regimen and baseline renal function. Monitor serum creatinine, BUN, urine output daily. Trough concentrations >3.3 µg/mL associated with increased nephrotoxicity risk (PMID 34409786).,Neurotoxicity: peripheral neurotoxicity (paresthesias, tingling, dizziness, ataxia) and rarely neuromuscular blockade reported. Dose-limiting in some patients (PMID 35702031).,Dose adjustment required for renal impairment: colistin is renally cleared; failure to reduce maintenance doses in renal dysfunction markedly increases toxicity.,Narrow therapeutic window: concentrations needed for efficacy overlap those causing nephrotoxicity; TDM strongly recommended in ICU settings.,Drug interactions: concurrent nephrotoxic agents (aminoglycosides, vancomycin, amphotericin B, NSAIDs, diuretics) substantially increase nephrotoxicity risk.,HOSPITAL-ONLY drug: colistin has no consumer or outpatient use. Requires specialist prescribing in intensive care or infectious disease settings.

Legal & regulatory status

US FDA

FDA-approved as colistimethate sodium (CMS) injection (Coly-Mycin M Parenteral) for acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa. Also…

WADA

Colistin is not listed on the WADA Prohibited List. It is a hospital-only intravenous antibiotic with no known performance-enhancing properties and is not a substance of concern in competitive sport.

Health Canada

Colistimethate sodium is approved in Canada (marketed as Colomycin) for the treatment of acute or chronic infections due to susceptible strains of gram-negative organisms. Health Canada labeling emphasizes use as a…