Colistin is a polymyxin antibiotic that has seen a resurgence in clinical use as a last-resort treatment against multidrug-resistant Gram-negative bacteria, often called “superbugs.” The use of colistin is carefully weighed by medical professionals. It is prescribed only when the risk of a life-threatening infection outweighs the risks associated with the drug itself.
How Colistin Works Against Bacteria
Colistin’s method of attack targets gram-negative bacteria, which are characterized by a protective outer membrane. Colistin, a polycationic peptide, is drawn to the negatively charged lipopolysaccharides (LPS) on this membrane. This initial interaction is driven by electrostatic forces.
The binding of colistin to the LPS displaces essential stabilizing ions like calcium and magnesium from the bacterial membrane. This disruption compromises the membrane’s structural integrity, creating a detergent-like effect that makes it unstable and permeable. This process is comparable to punching holes in the bacteria’s outer armor, causing the leakage of vital cellular contents.
This mechanism leads to the death of the bacterial cell. This approach is distinct from many other antibiotic classes that interfere with processes like cell wall construction or protein manufacturing. By directly disrupting the physical structure of the outer membrane, colistin provides a different mode of action against resistant pathogens.
When Doctors Prescribe Colistin
Colistin is reserved for severe and life-threatening infections where other antibiotic treatments have proven ineffective. It is a last-resort option for critically ill patients, particularly those in intensive care units, oncology wards, or who have undergone organ transplantation. Its application is a direct response to multidrug-resistant bacteria.
Colistin is effective against challenging gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. Infections caused by these bacteria can manifest as hospital-acquired pneumonia, bloodstream infections leading to sepsis, and complex urinary tract infections.
Given the severity of these infections, colistin is administered to effectively reach the infection site. For systemic infections, it is typically delivered intravenously. In cases where the infection is localized in the lungs, such as in patients with cystic fibrosis, an inhaled form may be used to deliver the drug directly to the area.
Serious Side Effects and Toxicity
The primary reason colistin is a last-resort treatment is its significant risk of toxicity. The potential for serious side effects requires that patients undergoing treatment are monitored carefully. These risks are a major consideration when weighing the drug’s benefits against the potential for harm.
A prominent concern is nephrotoxicity, or damage to the kidneys. Colistin use is associated with a 30% to 60% chance of this side effect occurring. This impairs the kidneys’ ability to function and requires diligent monitoring of renal function throughout treatment. The risk of kidney damage increases when colistin is used with other drugs that also have potential for nephrotoxicity.
Another significant risk is neurotoxicity, which involves damage to the nervous system. Symptoms can range from dizziness and slurred speech to tingling or numbness, particularly around the mouth or in the extremities. In severe instances, this can progress to weakness of the respiratory muscles and potentially apnea. These neurological effects are often related to the administered dose.
The Threat of Colistin Resistance
While colistin is a defense against multidrug-resistant infections, the emergence of bacteria that can resist its effects is a growing global health threat. For many years, resistance to colistin was uncommon and arose from spontaneous mutations in bacterial DNA. This has changed, raising concerns about the long-term viability of this last-resort antibiotic.
A significant development was the discovery of the mcr-1 gene, which is responsible for plasmid-mediated resistance that can spread rapidly. A plasmid is a small, mobile piece of DNA that can be easily transferred from one bacterium to another, even between different species. This allows resistance to spread much more rapidly than through simple mutation.
The rise of this resistance has been linked to the extensive use of colistin in agriculture, particularly as a growth promoter in livestock. This widespread use in animals created an environment where bacteria were pressured to develop resistance. The presence of the mcr-1 gene in bacteria from both animals and humans underscores the link between antibiotic use and resistance across different environments.