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Professional Version

Polymyxins Use in Animals


Melissa A. Mercer

, DVM, MS, DACVIM-LA, Virginia Maryland College of Veterinary Medicine

Reviewed/Revised Sep 2022 | Modified Nov 2022

Polymyxin B and polymyxin E, or colistin, belong to a group of cationic polypeptide antimicrobials. Because of toxicity, these drugs are most commonly administered topically or PO for treatment of intestinal infections.

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 ability to bind to the lipid-A moiety of lipopolysaccharide (LPS) has contributed to the use of polymyxin B in equine endotoxemia. Treatment with polymyxin B is most effective prior to the onset of endotoxemia because its mechanism of action requires it to bind to LPS prior to LPS binding to LPS-binding protein (LBP). Treatment with polymyxin B after clinical signs of endotoxemia have occurred is less efficacious.

The polymyxins' 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 decrease 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 hours after parenteral administration. Blood concentrations usually are low, because polymyxins bind to cell membranes as well as tissue debris and purulent exudates. The polymyxins undergo renal elimination mostly as degradation products, and their plasma half-lives are 3–6 hours. They are notably nephrotoxic and neurotoxic and, as such, systemic treatment at antimicrobial doses should be avoided. Neuromuscular blockade can occur 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 endotoxemia, bacilli, or Pseudomonas spp that are resistant to other drugs. Polymyxins are commonly administered PO as ophthalmic or otic preparations in combination products against susceptible organisms and are one of the components of triple antibiotic ointments available over the counter.

Recommended dose rates for polymyxins vary considerably. In horses, polymyxin B is typically used in an extralabel fashion and dosed at 6,000 U/kg, IV, as a slow bolus every 8 hours for antiendotoxic effects. Polymyxin is not labeled for oral or parenteral use for any veterinary species in the US.

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