Polymyxin B is a polypeptide antibiotic belonging to the polymyxin class, originally isolated from the bacterium Paenibacillus polymyxa. While initially developed in the late 1940s, its use was limited due to toxicity concerns. However, the rise of antibiotic resistance has led to polymyxins being re-employed as vital "last-resort" treatments for severe infections caused by challenging bacteria.
The Polymyxin Class of Polypeptide Antibiotics
Polymyxins are cationic, cyclic lipopeptide antibiotics that act like detergents on bacterial cell membranes. The two main members used clinically are polymyxin B and polymyxin E (colistin). They have similar core structures but differ by one amino acid and are administered differently, affecting how they behave in the body.
Mechanism of Action: The Membrane Disruptor
Polymyxin B kills bacteria by targeting the outer membrane of Gram-negative bacteria. Its action of disrupting the bacterial membrane makes it harder for bacteria to develop resistance compared to antibiotics that target internal processes. The mechanism involves polymyxin B binding to the outer membrane of Gram-negative bacteria, leading to destabilization and disruption of both the outer and inner membranes, ultimately causing cell death.
Clinical Use and Spectrum of Activity
Polymyxin B primarily targets Gram-negative bacteria and is not effective against Gram-positive bacteria, anaerobic bacteria, or certain resistant Gram-negative species. It is used for treating severe systemic infections caused by multidrug-resistant Gram-negative bacteria, such as bloodstream and urinary tract infections. It is also used in topical applications for minor infections and is a critical last-resort option for infections by bacteria like Pseudomonas aeruginosa and Acinetobacter baumannii.
Comparing Polymyxin B and Colistin
Polymyxin B and colistin (polymyxin E) are clinically important polymyxins, but they differ in how they are used and their properties.
| Feature | Polymyxin B | Colistin (Polymyxin E) |
|---|---|---|
| Administration Form | Given as the active sulfate salt. | Given as an inactive prodrug (colistimethate sodium) that is converted to the active form in the body. |
| Structure Difference | Contains D-phenylalanine at position 6. | Contains leucine at position 6. |
| Toxicity Profile | Direct administration may increase the risk of toxicity, particularly kidney damage. | Administering as a prodrug might reduce immediate toxicity, but kidney injury is still a major concern. |
| Elimination | Eliminated mainly by non-renal routes, not affected by kidney function. | Significant excretion of the prodrug by the kidneys, making management in patients with kidney problems more complicated. |
Significant Adverse Effects
Polymyxin B can cause dose-dependent toxicities that have limited its systemic use. The main side effects are kidney and nerve damage, though topical use is generally safer. The most common serious side effect of systemic treatment is nephrotoxicity, requiring close monitoring of kidney function. Neurotoxicity can cause symptoms like irritability, weakness, dizziness, and tingling, and in rare cases, muscle weakness.
The Challenge of Polymyxin Resistance
Bacteria are developing resistance to polymyxins by changing their outer membrane to prevent the antibiotic from binding. This can happen through chromosomal changes that modify the bacterial outer membrane using genes regulated by systems like PhoP/PhoQ and PmrA/PmrB, adding positive charges that repel polymyxin. Plasmid-mediated resistance, facilitated by genes such as the mcr family, also modifies the outer membrane and can spread rapidly between bacteria.
Conclusion
Polymyxin B, a potent polypeptide antibiotic, serves as a crucial last-resort treatment for severe infections caused by multidrug-resistant Gram-negative bacteria. Its unique method of disrupting the bacterial cell membrane makes it effective against bacteria resistant to other antibiotics. However, its use requires careful oversight due to risks of kidney and nerve damage, and its future effectiveness is threatened by growing bacterial resistance. Responsible use and continued research are vital to preserve polymyxin B as a treatment option.
More Information
For further reading on antimicrobial resistance, a key challenge discussed in this article, you can explore resources from the {Link: World Health Organization https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance}).
This is an external, authoritative source for additional information.
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