Colistin is an antibiotic in the polymyxin class, produced by the bacterium Bacillus colistinus. It is available in two primary forms: colistin sulfate, for application to the skin or oral use, and colistimethate sodium, administered by injection or inhalation. The oral form is used to treat infections in the stomach and intestines.
Colistin is prescribed for severe bacterial infections, particularly those that have not responded to other antibiotics. It is effective against gram-negative bacteria, and the injectable form is reserved for serious infections that may require hospitalization. Due to its specific properties, it is not used for all types of bacterial infections.
The Resurgence of a Last-Resort Antibiotic
Discovered in 1947, colistin was an early antibiotic. As newer and safer antibiotics were developed, its use sharply declined by the 1980s. The primary reason for this was its recognized toxicity, particularly the risk of damage to the kidneys and nervous system. For decades, it remained a medication of last resort, overshadowed by alternatives with fewer side effects.
Colistin’s return is a direct response to the global rise of multidrug-resistant (MDR) bacteria, which have evolved to survive treatment with many common antibiotics. Colistin has re-emerged as a necessary option for treating infections caused by some of the most challenging gram-negative pathogens. These include Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae.
These MDR organisms can cause severe conditions, particularly in hospital settings. They are responsible for ventilator-associated pneumonia, bloodstream infections, and infections in patients with compromised immune systems. In these situations, where other antibiotics have failed, colistin is deployed as a final line of defense.
How Colistin Works
The effectiveness of colistin is due to its method of action, which directly targets the outer membrane of gram-negative bacteria. This outer layer, composed of a substance called lipopolysaccharide (LPS), is a protective barrier that many other antibiotics cannot penetrate. Colistin’s structure allows it to bind to and disrupt this membrane.
This interaction is comparable to how a detergent breaks down grease. Colistin molecules insert themselves into the bacterial membrane, destabilizing its structure. This process leads to the formation of pores in the membrane, causing the cellular contents to leak out. The result is the death of the bacterial cell.
This mechanism makes colistin potent against bacteria like P. aeruginosa and A. baumannii. It attacks a component of their structure that is not present in gram-positive bacteria or fungi, explaining its specific range of activity. This direct assault on the cell membrane distinguishes it from many antibiotics that work by interfering with processes like cell wall synthesis or protein production.
The Risks of Colistin Treatment
The primary reason colistin is reserved as a last-resort treatment is its potential for toxic side effects. The two most prominent concerns are nephrotoxicity, which is damage to the kidneys, and neurotoxicity, which involves damage to the nervous system. These risks necessitate a careful balancing of the drug’s benefits against its potential harm.
Nephrotoxicity is a common complication of colistin therapy. The drug is primarily cleared by the kidneys, and it can directly harm the kidney tubules responsible for filtering waste from the blood. This damage can lead to decreased urine output and an accumulation of waste products, which is detectable through blood tests. If signs of kidney impairment appear, doctors may need to adjust the dosage or discontinue the therapy.
Neurotoxicity can manifest in various ways, affecting both the central and peripheral nervous systems. Patients may experience symptoms such as dizziness, vertigo, numbness or a tingling sensation around the mouth and in the extremities, and slurred speech. In more severe cases, muscle weakness can occur, and patients are often advised to avoid activities that require full mental alertness.
The Challenge of Colistin Resistance
While colistin has been a reliable last line of defense, a growing number of bacteria are developing ways to survive exposure to it. This development of resistance is a public health concern because it threatens to render this final option ineffective. The emergence of bacteria that can withstand colistin treatment means some infections may become untreatable.
A significant discovery has been the identification of a specific gene that confers resistance to colistin. Known as the mobilized colistin resistance gene, or mcr-1, its discovery signaled a shift in the landscape of antibiotic resistance. This gene produces an enzyme that modifies the bacterial cell membrane, preventing colistin from binding to it.
The mcr-1 gene’s location on a plasmid is a significant concern. Plasmids are small, mobile pieces of DNA that bacteria can easily exchange with one another, even between different species. This horizontal gene transfer allows resistance to spread much more rapidly than through simple mutation. The presence of mcr-1 on a plasmid means that resistance can quickly disseminate among various populations of bacteria, accelerating a global health challenge.