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Polymyxin B
Colistin

Polymyxins

The polymyxins are a family of compounds produced by Bacillus polymyxa and related bacteria. Only polymyxins B and E (colistin) are used therapeutically. Structurally, the polymyxins are cyclic polypeptides with a long hydrophobic tail. They act like cationic detergents by binding to the cell membrane and causing the leakage of essential cytoplasmic contents. The effect is not entirely selective, and both polymyxin B and colistin exhibit high toxicity.

Colistin is a derivative of polymyxin B in which up to five diaminobutyric acid residues are substituted with sulphomethyl groups and is better tolerated and more quickly excreted than the parent compound. Colistin exhibit diminished antibacterial activity, but the precise loss in activity is difficult to estimate because the compound spontaneously break down to the more active parent.

The antibacterial spectrum of the polymyxins encompasses most Gram-negative bacteria except Proteus spp., but the importance of these antibiotics is based on their activity against P. aeruginosa. With the appearance of antipseudomonal b-lactam agents, aminoglycosides, and fluoroquinolones, the polymyxins have virtually fallen into disuse for systemic therapy, although they are still used in some topical preparations. They are also included in selective decontamination regimens aimed at preventing endogenous infection in profoundly neutropenic patients and there are advocates of the use of colistin in cystic fibrosis by instillation into the lungs of those suffering exacerbation of pseudomonal infection. However recently the growing resistance to carbapenems and diffusion of multi and pan resistant Gram negative strains, has forced the clinicians to resurrect polymyxins.

 



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