Chapter 15 : Antibiotics That Affect Membrane Permeability

Abstract:

The polymyxins are a group of cyclic, polycationic peptide antibiotics with a fatty acid chain attached to the peptide through an amide linkage. They are produced by fermentation of strains of Bacillus polymyxa. Polymyxins B and E (colistin) are the least toxic and are the only polymyxins used clinically. These antibiotics contain a 7-amino-acid ring attached to a 3-amino-acid tail, to which is attached a fatty acyl group. It has been suggested that the fatty acid part of the polymyxin molecule penetrates into the hydrophobic region of the outer membrane and the ammonium groups interact with the lipopolysaccharides and phospholipids, competitively displacing divalent cations (calcium and magnesium) from the negatively charged phospholipid group of the membrane lipids. This displacement disrupts membrane organization and increases the permeability of the membrane. Polymyxins B and E are active almost exclusively against aerobic gram negative bacilli. In particular, they exhibit quite good activity against Pseudomonas aeruginosa. In the past, these polymyxins were often used for the treatment of P. aeruginosa infections. Nowadays, because of the availability of effective and less toxic drugs such as gentamicin, tobramycin, amikacin, ticarcillin, piperacillin, and ceftazidime, polymyxins are not the antibiotics of choice to treat infections caused by this bacterium.