Polymyxin

Polymyxin is a type of antibiotic, specifically a lipopeptide, that is used to treat infections caused by Gram-negative bacteria. There are five different types of polymyxin, labeled A-E, but only polymyxin B and E (also known as colistin) are used in clinical practice.

Polymyxins work by interacting with the lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, disrupting the cell membrane and leading to cell death. They are often used as a last resort treatment for multidrug-resistant infections.

History

Polymyxins were first isolated in 1947 from the bacterium Bacillus polymyxa. Initially, they were widely used to treat infections, but their use declined in the 1970s due to concerns about nephrotoxicity and neurotoxicity. However, the rise of multidrug-resistant bacteria in the 21st century has led to a resurgence in their use.

Medical uses

Polymyxins are used to treat infections caused by multidrug-resistant Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. They are often used when other antibiotics are ineffective.

Side effects

The most common side effects of polymyxins are kidney damage and nerve damage. Other side effects can include skin rash, dizziness, and fever.

Mechanism of action

Polymyxins work by binding to the LPS in the outer membrane of Gram-negative bacteria. This disrupts the cell membrane, causing the cell to leak and eventually die.

Resistance

Resistance to polymyxins can occur through various mechanisms, including changes in the LPS, efflux pumps, and modification of the target site.

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  Chemical structure of Colistin
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  Chemical structure of Polymyxin B
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  Schematic of Polymyxin structure
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  Biosynthesis of Polymyxin D