Polymyxin B

Absorption

Administration by the oral route does not lead to absorption.

Toxicity

Nephrotoxicity can occur in patients as polymyxin B is thought to accumulate in renal cells after renal tubular reabsorption. This accumulation can lead to apoptosis of renal cells and decrease in renal function. In recent studies, acute kidney injury (AKI) has been seen in 31.3% to 39.4% of patients receiving polymyxin B.
Overdose cases can cause neuromuscular block leading to apnea, muscular weakness, vertigo, transient facial parasthesia, slurred speed, vasomotor instability, visual disturbance, confusion, psychosis, and respiratory arrest. Renal failure has also been seen through decreased urine output, and increased serum concentrations of blood urea nitrogen.
Overdose of polymyxin B is treated by stopping the drug and beginning symptomatic treatment. Intravenous administration of mannitol may enhance renal clearance, and hemodialysis may manage renal complications.
Safety of polymyxin B has not been established in pregnancy, breast feeding, pediatrics, and geriatrics. Polymyxin B should no be used in pregnancy unless the benefit outweighs the risk. Nursing mothers should either stop nursing or stop polymyxin B treatment depending on the risks to both the mother and child. Pediatric patients should be frequently monitored for renal function and no dosing information is available in children under 2 years of age. Geriatric patients should have renal function assessed before and regularly during therapy.

Description

Polymyxin B was isolated by Wellcome Research Laboratories, in 1949, from the mixture of polymyxins A, B, C, and D produced byBacillus polymyxa. It was later separated into the major component, B1, and the minor component, B2. Polymyxin B is a basic polypeptide and shows strong activity against gram-negative bacteria, but its activity against gram-positive bacteria, Mycobacterium, and fungi is weak. Because of its toxicity, it is used carefully by intramuscular injection for resistant Pseudomonas aeruginosa infections, e.g., sepsis. Polymyxin B is used orally to sterilize the gut in leukemic patients, intraspinally for meningitis, or topically.

The Uses of Polymyxin B

Antibacterial Aerosporin.

Indications

Polymyxin B is indicated for the treatment of infections of the urinary tract, meninges, and blood stream, caused by susceptible strains of Pseudomonas aeruginosa.

Background

Polymyxin B was discovered in the 1940s. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic. All gram-positive bacteria, fungi, and the gram-negative cocci, are resistant. It is appropriate for treatment of infections of the urinary tract, meninges, and blood stream, caused by susceptible strains of Pseudomonas aeruginosa. Polymyxin B has a narrow therapeutic index and so its use is limited and unlikely to be used first line.

Definition

ChEBI: A polymyxin having a 6-methylheptanoyl group at the amino terminus.

brand name

(GlaxoSmithKline); Poly-Rx (X Gen).

Contact allergens

Active against Gram-negative bacteria, Polymyxin B is a mixture of Polymyxin B1 and B2. Sensitization occurs by topical, ophthalmic, and otic preparations. Cosensitization is frequent with other topical antibiotics like neomycin or bacitracin.

Pharmacokinetics

Polymyxin B is an antibiotic that disrupts the outer cell membrane of Gram negative bacteria, binds and neutralizes lipopolysaccharide, and inhibits respiration of Gram-negative bacterial cells. Polymyxin B can be given by a number of routes to treat susceptible Gram negative bacterial infections. Absorption of the drug is poor (though not necessary for most of its activity) and the excreted drug is unchanged by metabolic processes. Polymyxin B is generally indicated for susceptible Gram negative infections of the urinary tract, meninges, and blood stream.

Metabolism

There is little data available for the metabolism of polymyxin B. In one study, <1% of polymyxin B was eliminated through the kidneys and it had not been metabolised. Polymyxin B has also been found in bile, not having undergone metabolic processes.