Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules called nonribosomal peptides. Structurally these agents are cationic cyclic lipopeptides composed of a cyclic heptapeptide core, a tripeptide side chain and an N-terminal fatty acyl tail, with multiple 2,4-diaminobutyric acid residues that give them strong positive charge at physiological pH. The primary antibacterial action is mediated by electrostatic interaction with lipid A in lipopolysaccharide of the outer membrane, displacement of divalent cations, outer membrane destabilization and subsequent disruption of the cytoplasmic membrane leading to rapid bactericidal activity against susceptible Gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacterales. Clinically relevant forms include polymyxin B sulfate and polymyxin E in the form of colistin or the prodrug colistimethate sodium, with uses ranging from topical and inhalation formulations to systemic therapy for multidrug resistant infections; adverse effects to monitor include nephrotoxicity and neurotoxicity. Biosynthesis proceeds via nonribosomal peptide synthetases and the resulting product is typically a mixture of closely related peptide analogs rather than a single homogeneous molecule.
Polymyxin drug substance and formulations are multicomponent mixtures in which the major active constituents and related substances are well characterized; for polymyxin B the dominant components are polymyxin B1 and B2 while for polymyxin E the dominant components are colistin A and colistin B, and these major components typically account for roughly 70 to 95 percent of the total peptide content depending on manufacturing and purification. Typical related compounds and impurities include minor polymyxin homologs (B3, B6 and other sequence variants), N-deacylated derivatives often termed polymyxin nonapeptides, desmethyl and epimeric species, hydrolysis products and low-level oxidized variants; the combined level of these related substances is commonly found in the single-digit percent range up to about 10 to 20 percent in less purified materials, with individual impurity limits in finished specifications often set at low percentages or parts-per-million depending on regulatory monographs and the intended dosage form. Analytical characterization relies on orthogonal methods such as reversed-phase HPLC with UV and MS detection, LC-MS/MS for structural identification, amino acid analysis and peptide mapping, and these methods are used to quantify the fractional amounts of each major component and to control impurity levels in acceptance testing.
Polymyxin B is used in some topical ophthalmic preparations, commonly in combination with other antibiotics such as trimethoprim, for bacterial conjunctivitis; it is not effective against viral conjunctivitis and an ocular care professional should be consulted before use.
Polymyxins bind to lipid A of lipopolysaccharide in the outer membrane of Gram-negative bacteria, displace divalent cations that stabilize the membrane, increase membrane permeability and cause rapid disruption of both outer and inner membranes, leading to cell lysis and bactericidal activity.
No, polymyxins have minimal to no clinically useful antifungal activity and are not used to treat fungal infections.
Topical otic products that include polymyxin B exist for external ear infections, but use in the ear should follow a clinician recommendation; caution is required when the tympanic membrane may be perforated and systemic or ototoxicity risks should be considered before using any antibiotic ear drops.
