polimiksin

Polymyxins are a class of cyclic cationic peptide antibiotics produced by Bacillus polymyxa. The two clinically used members are polymyxin B and colistin (polymyxin E). They are primarily active against Gram-negative bacteria and are used as a last-resort option for infections caused by multidrug-resistant organisms.

Polymyxins kill by binding to lipopolysaccharide and phospholipids in the outer membrane of Gram-negative bacteria. This interaction disrupts the bacterial cell membrane, leading to leakage of cellular contents and rapid cell death. They are considered bactericidal and their activity is concentration-dependent.

Their spectrum is mainly limited to Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales such as Klebsiella and Escherichia coli. They have little activity against most Gram-positive bacteria and anaerobes. In modern practice, colistin is commonly used as a salvage therapy for MDR infections, while polymyxin B is used for systemic infections and certain topical indications. Inhaled formulations of colistin are used for pulmonary infections, particularly in cystic fibrosis patients.

Pharmacokinetics: Colistin is administered as an inactive prodrug (colistimethate sodium); polymyxin B is administered as the active compound. Both are poorly absorbed from the gut; they are administered intravenously for systemic infections. Dosing requires adjustment in renal impairment and careful monitoring due to nephrotoxicity and neurotoxicity.

Resistance and stewardship: Resistance can arise through modifications of the LPS target, reducing binding of the drugs, and via plasmid-mediated mechanisms (mcr genes). The emergence of resistance underscores the need for antimicrobial stewardship and combination therapy in MDR infections.

History: Discovered in the 1940s from Bacillus polymyxa; use declined due to toxicity but resurged in the 2000s for MDR pathogens.