colistimethate

Colistimethate sodium, also known as colistin methanesulfonate, is a water-soluble prodrug of colistin (polymyxin E). It is an antibiotic used to treat infections caused by certain Gram-negative bacteria, particularly when they are resistant to many other agents. Colistimethate itself is largely inactive until it is converted to active colistin in the body.

Colistin acts by interacting with the lipopolysaccharide and phospholipids in the outer membrane of Gram-negative bacteria, disrupting membrane integrity and causing cell death. The prodrug form Colistimethate is converted in vivo to the active cationic peptide. The antibiotic is primarily active against several Gram-negative pathogens, including Pseudomonas aeruginosa, Acinetobacter species, and Klebsiella pneumoniae, with activity that varies among strains.

Because it is poorly absorbed from the gastrointestinal tract, colistimethate is given parenterally for systemic infections or by inhalation for respiratory infections. It is excreted renally, and dosing often requires adjustment in renal impairment. Inhaled formulations deliver drug directly to the airways and are used for respiratory infections, including those caused by multidrug-resistant organisms in cystic fibrosis and non-CF patients.

Adverse effects are a major consideration. The most significant toxicities are nephrotoxicity and neurotoxicity, including paresthesias, dizziness, and, in severe cases, neuromuscular blockade or respiratory depression. Risk increases with higher doses, prolonged therapy, and concomitant nephrotoxic drugs. Monitoring of kidney function and careful dose adjustment are recommended.

Resistance can emerge through modifications to lipopolysaccharide or reduced drug uptake. Colistin has a long history of use and, in the context of rising multidrug resistance, remains a critical but carefully managed option in appropriate infections.