Polymyxin B

In plain language

Polymyxin B is a last-resort antibiotic for serious Gram-negative infections, the sibling of colistin, discovered in the same soil bacterium in the 1940s. It is also the antibacterial ingredient in many over-the-counter skin ointments.

The injectable form is saved for bacteria that resist other drugs, and like colistin it can damage the kidneys and nerves. The topical form, usually combined with bacitracin and neomycin, has been a household staple for minor cuts and scrapes for decades.

For students

Polymyxin B is a cyclic lipodecapeptide (about 1,203 Da for the B1 component) from Bacillus polymyxa, differing from colistin (polymyxin E) by a D-phenylalanine at position 6. It is administered as the directly active sulfate salt, in contrast to colistimethate, which simplifies pharmacokinetics but removes formulation-driven stability advantages.

The direct-acting form made polymyxin B attractive for serious infections when carbapenem resistance spread, and a randomized trial (RCT n=152, Nebot et al./the 2020 Lancet Infectious Diseases study) found lower nephrotoxicity versus colistin, shifting practice toward polymyxin B for bloodstream infections. Topical triple-antibiotic ointments (polymyxin B, bacitracin, neomycin) exploit its membrane-permeabilizing activity on skin, where systemic toxicity is irrelevant; contact dermatitis to neomycin, not polymyxin, is the main topical concern.

For researchers and instructors

Biochemistry. The D-Phe6 substitution versus polymyxin E modestly changes receptor-free membrane interaction; both bind lipid A, neutralizing endotoxin as well as permeabilizing membranes, a dual action relevant to sepsis adjunct discussions.

Pharmacology. Directly active drug, no prodrug conversion lag, dosing in mg/kg of the sulfate; nephrotoxicity slightly lower than colistimethate per head-to-head data; CSF penetration negligible without intrathecal dosing.

Human evidence. A randomized comparison (n=152) and multiple cohort studies support lower kidney toxicity versus colistimethate; definitive superiority trials for infections remain absent, keeping both as rescue agents.

Teaching point. Teaches comparative sibling pharmacology (direct-acting versus prodrug) and how a single amino acid difference plus formulation choice shapes clinical practice.