Polymixins

Detailed article on polymyxins, a class of antibiotics

Synonyms

Polymyxins

Drug Information
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Polymyxins are a class of antibiotics that are particularly effective against Gram-negative bacteria. They are cyclic polypeptides with a long hydrophobic tail, which allows them to interact with the bacterial cell membrane, disrupting its integrity and leading to cell death. Polymyxins are considered last-resort antibiotics due to their nephrotoxicity and neurotoxicity, but they are crucial in treating infections caused by multidrug-resistant organisms.

History

Polymyxins were first discovered in the late 1940s from the bacterium Bacillus polymyxa. The two most commonly used polymyxins in clinical practice are Polymyxin B and Colistin (also known as Polymyxin E). Their use declined with the advent of less toxic antibiotics, but they have seen a resurgence due to the rise of antibiotic resistance.

Mechanism of Action

Polymyxins target the lipopolysaccharide (LPS) layer of the outer membrane of Gram-negative bacteria. They bind to the LPS and disrupt the membrane, increasing its permeability. This leads to leakage of cellular contents and ultimately bacterial cell death. The specificity for Gram-negative bacteria is due to the presence of LPS, which is absent in Gram-positive bacteria.

Clinical Uses

Polymyxins are used to treat severe infections caused by multidrug-resistant Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. They are often used in combination with other antibiotics to enhance efficacy and reduce the development of resistance.

Adverse Effects

The use of polymyxins is limited by their potential for nephrotoxicity and neurotoxicity. Nephrotoxicity manifests as acute kidney injury, while neurotoxicity can present as dizziness, weakness, and paresthesia. Monitoring of renal function is essential during treatment.

Resistance

Resistance to polymyxins is relatively rare but has been increasing. Mechanisms of resistance include modification of the LPS target, efflux pumps, and enzymatic degradation. The emergence of the mcr-1 gene, which confers plasmid-mediated resistance to colistin, is of particular concern.

Research and Development

Ongoing research aims to develop new polymyxin derivatives with reduced toxicity and improved efficacy. Efforts are also focused on understanding resistance mechanisms and developing strategies to overcome them.

Also see

• Antibiotic resistance
• Gram-negative bacteria
• Colistin
• Nephrotoxicity
• Antibiotic stewardship