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Polymyxins

By

Dawn Merton Boothe

, DVM, PhD, Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University

Last full review/revision Nov 2015 | Content last modified Nov 2015

This group of polypeptide antibiotics includes polymyxin B and polymyxin E, or colistin. Because of toxicity, these drugs are most commonly used topically, or PO for treatment of intestinal infections. Colistimethate is a form of colistin intended for parenteral administration. Polymyxins are bactericidal; they interact strongly with phospholipids in bacterial cell membranes and radically disrupt their permeability and function. The polymyxins are more effective against gram-negative than gram-positive bacteria. Their rather narrow spectrum includes Enterobacter, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella, Pseudomonas spp, and Escherichia coli. Most Proteus or Neisseria spp are not susceptible. Although intrinsic bacterial resistance to polymyxins is recognized, resistance is uncommon and is chromosome-dependent only. Polymyxins act synergistically when combined with potentiated sulfonamides, tetracyclines, and some other antibacterials; they also reduce the activity of endotoxins in body fluids and may be beneficial in endotoxemia. Their action is inhibited by divalent cations, unsaturated fatty acids, and quaternary ammonium compounds.

Polymyxins are not absorbed after PO or topical administration; plasma concentrations peak ~2 hr after parenteral administration. Blood concentrations usually are low, because polymyxins bind to cell membranes as well as tissue debris and purulent exudates. The polymixins undergo renal elimination mostly as degradation products, and their plasma half-lives are 3–6 hr. They are notably nephrotoxic and neurotoxic and, as such, systemic therapy at antimicrobial doses should be avoided. Neuromuscular blockade can be seen at higher concentrations. Intense pain at sites of injection and hypersensitivity reactions also can be expected. Polymyxin B is a potent histamine releaser. The main indication for parenteral use of polymyxins is life-threatening infection due to gram-negative bacilli or Pseudomonas spp that are resistant to other drugs. Polymyxins are also used PO against susceptible intestinal infections. Anti-endotoxin binding activity is an additional therapy via slow IV bolus. Topical application is common, eg, for otitis externa.

Recommended dose rates for polymyxins vary considerably. A general guideline is 20,000 U/kg, PO, bid; 5,000 U/kg, IM, bid; 50,000–100,000 U by intramammary infusion; 100,000 U intrauterine in cattle. IV administration of polymyxins is potentially dangerous.

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