Colistin

Summary

Colistin (polymyxin E) is a cyclic polycationic lipopeptide antibiotic derived from Bacillus polymyxa subspecies colistinus. It is used as a last-resort antibiotic against multidrug-resistant (MDR) Gram-negative infections, including those caused by carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Administered as a prodrug (colistimethate sodium, CMS) for parenteral and inhalation use, or as colistin sulfate for oral/topical use.

Mechanism of Action

Binds to lipopolysaccharide (LPS) and phospholipids in the outer membrane of Gram-negative bacteria, displacing divalent cations (Ca²⁺, Mg²⁺), disrupting membrane integrity, causing increased permeability and cell death. Also acts as a detergent-like agent against bacterial membranes.

Routes of Administration

Goals & Uses

• Intestinal decontaminationAntimicrobialLow
• Treatment of carbapenem-resistant Klebsiella pneumoniae infectionsAntimicrobialModerate
• Inhalation therapy for pulmonary infections in cystic fibrosisAntimicrobialModerate
• Treatment of carbapenem-resistant Acinetobacter baumannii infectionsAntimicrobialModerate
• Treatment of multidrug-resistant Pseudomonas aeruginosa infectionsAntimicrobialModerate

Contraindications

• Severe pre-existing renal impairment (without dose adjustment)RenalHigh
• Known hypersensitivity to colistin or polymyxinsAllergyHigh
• Myasthenia gravisNeuromuscular DiseaseHigh

Adverse Effects

• NeurotoxicityNeurologicalUncommon
• Injection site reactionsLocalCommon
• Electrolyte disturbancesMetabolicUncommon
• BronchospasmRespiratoryUncommon
• Apnea / respiratory failureRespiratoryRare
• NephrotoxicityRenalCommon

Drug Interactions

• AminoglycosidesHigh
• Non-depolarizing neuromuscular blocking agentsHigh
• VancomycinModerate
• NSAIDsModerateMay increase renal risk in susceptible patients
• Loop diuretics (e.g., furosemide)Moderate

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentRelative
• Elderly patientsAgeRelative
• Neonates and premature infantsPediatricRelative

Regulatory Status

• European UnionApprovedApproved: Serious infections caused by certain Gram-negative bacteria sensitive to colistin, Adjunct inhaled therapy in cystic fibrosis patients with chronic pulmonary Pseudomonas aeruginosa infectionsEMA-approved products include Colomycin (inhaled and IV). Restricted use emphasized due to resistance concerns.
• United StatesApprovedApproved: Acute or chronic infections due to susceptible Gram-negative bacilli (colistimethate sodium, parenteral), Intestinal infections due to enteropathogenic Escherichia coli (colistin sulfate, oral)FDA-approved. Colistimethate sodium (Coly-Mycin M) for parenteral use. Off-label use for MDR Gram-negative infections is common.
• United KingdomApprovedApproved: Serious infections due to susceptible Gram-negative organisms, Chronic pulmonary infections in cystic fibrosis (inhaled)MHRA-approved. Listed as a reserve antibiotic; use guided by antimicrobial stewardship programs.

Approved in the US, EU, and UK for serious Gram-negative infections. Classified as a critically important antimicrobial by WHO. Use is reserved for infections with limited or no alternative treatment options due to nephrotoxicity and neurotoxicity concerns.

Evidence & Sources

No sources recorded yet.