Colistin
Polymyxin lipopeptide antibiotic that disrupts gram-negative bacterial outer membranes, used as last-line therapy for MDR infections.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C52H98N16O13 (Colistin A) |
| Molecular Weight | 1155.4 Da |
| CAS Number | 1066-17-7 (sodium salt) |
| Peptide Class | Cyclic Lipopeptide (Polymyxin family) |
| Origin | Paenibacillus polymyxa subsp. colistinus |
| Route | IV, inhaled, topical |
Structure
Colistin (polymyxin E) is a mixture of cyclic lipopeptides (colistin A and B) produced by Paenibacillus polymyxa. It consists of a heptapeptide ring with a tripeptide side chain acylated with a fatty acid. Colistin A has 6-methyloctanoic acid and colistin B has 6-methylheptanoic acid as the fatty acid component.
Mechanism of Action
Colistin binds to lipopolysaccharide (LPS) in the gram-negative outer membrane through electrostatic interaction between cationic diaminobutyric acid residues and anionic lipid A phosphate groups. The fatty acid tail displaces stabilizing divalent cations, disrupting membrane integrity and causing cell lysis. It also has some endotoxin-binding activity.
Clinical Applications
- MDR gram-negative infections: Pseudomonas, Acinetobacter, Klebsiella carbapenemase producers
- Ventilator-associated pneumonia: Inhaled colistin as adjunct
- Cystic fibrosis: Inhaled for Pseudomonas exacerbations
- Intrathecal/intraventricular: CNS infections with resistant gram-negatives
Pharmacokinetics
- Half-life: 5-7 hours (colistin base)
- Protein binding: ~50%
- Elimination: Renal (primarily as inactive metabolites)
- Loading dose: Required to achieve therapeutic levels
- Route: IV (colistimethate sodium), inhaled, intrathecal
Safety and Side Effects
Nephrotoxicity (dose-limiting, 20-60%), neurotoxicity (paresthesias, dizziness, neuromuscular blockade, seizures), and hypersensitivity. Narrow therapeutic index. Colistimethate is less toxic than colistin sulfate.
References
- Falagas, M.E., & Kasiakou, S.K. (2006). Colistin: the revival of polymyxins. Lancet Infectious Diseases, 6, 113-122.
- Nation, R.L., & Li, J. (2009). Colistin: clinical pharmacology. Clinical Pharmacokinetics, 48, 623-637.
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