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approvedImmune & Inflammation

Colistin

Also known as: Polymyxin E, Colistimethate Sodium, CMS, Coly-Mycin M, Colistin Sulfate

Colistin (polymyxin E) is a cyclic lipopeptide antibiotic discovered in 1949, used as a critical last-resort treatment for multidrug-resistant gram-negative infections. Administered as the prodrug colistimethate sodium (CMS), it is particularly important for treating carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Despite nephrotoxicity and neurotoxicity risks, the global rise of extensively drug-resistant gram-negative bacteria has made colistin indispensable in modern critical care.

3 cited references·5 researched benefits

Quick Answer

Colistin (polymyxin E) is a cyclic lipopeptide antibiotic approved as a last-resort treatment for multidrug-resistant gram-negative infections. Administered as the prodrug colistimethate sodium, it kills bacteria by disrupting their outer membrane through binding to lipopolysaccharide. Colistin is critical for treating carbapenem-resistant infections, particularly in ICU settings. Its half-life is approximately 5 hours. Nephrotoxicity occurs in 30-60% of patients, requiring careful monitoring and dose adjustment.

Key Facts

Mechanism
Colistin is administered as the inactive prodrug colistimethate sodium (CMS), which undergoes hydrolysis in plasma and tissues to release active colistin. Like polymyxin B, active colistin kills gram-negative bacteria by binding electrostatically to lipid A of lipopolysaccharide (LPS) in the outer membrane, displacing stabilizing divalent cations. Its fatty acyl chain inserts into the outer membrane, disrupting its barrier function. This self-promoted uptake leads to inner membrane permeabilization, leakage of intracellular contents, and rapid cell death. The prodrug formulation allows for aerosolized delivery directly to the lungs for pulmonary infections, achieving high local concentrations with reduced systemic toxicity.
Research Status
approved
Half-Life
~5 hours (active colistin); CMS prodrug: ~2-3 hours
Molecular Formula
C₅₂H₉₈N₁₆O₁₃
Primary Use
Immune & Inflammation
Table of Contents

Benefits

  • Critical last-resort option for carbapenem-resistant gram-negative infections with no other treatmentstrong
  • Aerosolized CMS achieves high pulmonary concentrations for ventilator-associated pneumonia (VAP)strong
  • Rapid bactericidal activity through membrane disruption mechanismstrong
  • Synergistic combinations with carbapenems, rifampin, and fosfomycin against XDR organismsmoderate
  • Endotoxin neutralization provides additional anti-inflammatory benefit in gram-negative sepsismoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous (CMS prodrug)9 million IU loading dose, then 4.5 million IU every 12 hoursEvery 12 hoursStandard dosing for systemic MDR gram-negative infections; adjust for renal function
Nebulized (CMS prodrug)1-2 million IU per dose2-3 times dailyAdjunct for MDR gram-negative pneumonia; used alongside systemic therapy for VAP
Intrathecal/Intraventricular125,000 IU (approximately 10 mg CMS) dailyDailyFor MDR gram-negative meningitis or ventriculitis not responding to systemic therapy

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nephrotoxicity in 30-60% of patients receiving systemic therapyserious
  • Neurotoxicity including paresthesias, dizziness, and confusionserious
  • Bronchospasm with inhaled colistimethate sodiumcommon
  • Neuromuscular blockade and respiratory depression at high dosesserious
  • Injection site pain with intramuscular administrationcommon

Frequently Asked Questions

Why is colistin resistance so concerning?
Colistin resistance, particularly mediated by the plasmid-borne mcr-1 gene discovered in 2015, is one of the most alarming developments in infectious disease. Because colistin is often the last available treatment for extensively drug-resistant gram-negative bacteria, resistance to it creates truly untreatable infections. The mcr-1 gene is especially dangerous because it can transfer between bacterial species via horizontal gene transfer, potentially spreading resistance rapidly through healthcare environments.
Is colistin or polymyxin B better for treating MDR infections?
Current evidence and guidelines increasingly favor polymyxin B for systemic infections because it is administered as the active drug (not a prodrug), achieving more predictable and consistent plasma concentrations. Colistimethate sodium (CMS) conversion to active colistin is variable and incomplete, making dosing less reliable. However, CMS is preferred for aerosolized delivery to treat pulmonary infections because it causes less airway irritation than polymyxin B sulfate.
How does colistin resistance develop?
Colistin resistance occurs through modification of lipid A — the target molecule in LPS. Bacteria add positively charged groups (such as phosphoethanolamine or 4-amino-4-deoxy-L-arabinose) to lipid A, reducing its negative charge and preventing colistin binding. This can occur through chromosomal mutations in regulatory genes (mgrB, pmrAB, phoPQ) or through acquisition of plasmid-mediated mcr genes. Agricultural use of colistin in livestock has been identified as a major driver of resistance.
Can colistin be used for urinary tract infections?
Yes. Because colistimethate sodium (CMS) is primarily excreted by the kidneys, high concentrations of active colistin accumulate in the urinary tract, making it effective for MDR gram-negative urinary tract infections (UTIs). Paradoxically, the renal excretion that contributes to nephrotoxicity also makes colistin particularly useful for urinary infections caused by carbapenem-resistant organisms.

References

  1. 1
    Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications(2015)PubMed ↗
  2. 2
    Colistin: recent data on pharmacodynamics and clinical outcome from the International Society of Chemotherapy(2019)PubMed ↗
  3. 3
    Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China(2016)PubMed ↗

Latest Research

Last updated: 2026-02-19