Polymyxin is a class of antibiotic used to treat serious infections caused by gram-negative bacteria, particularly when those bacteria have become resistant to every other available drug. Two forms are used in medicine: Polymyxin B and Polymyxin E (better known as colistin). Often called “last-resort” antibiotics, polymyxins are among the few remaining options for infections that don’t respond to anything else.
How Polymyxins Kill Bacteria
Gram-negative bacteria have a protective outer membrane that shields them from many antibiotics. Polymyxins work by punching holes in that membrane. The drug carries a strong positive electrical charge, which attracts it to the negatively charged surface of the bacterial membrane. Once there, it displaces the calcium and magnesium ions that normally hold the membrane together, binding with at least three times the strength of those natural ions.
Without those stabilizing ions, the membrane develops temporary cracks. Cell contents leak out, and the bacterium dies. This membrane-targeting approach is one reason polymyxins remain effective against bacteria that have learned to resist other antibiotics, which typically work by interfering with internal processes like protein or DNA production.
Why They Fell Out of Use and Came Back
Polymyxins were first discovered in 1947, isolated from a soil bacterium called Paenibacillus polymyxa. They were approved for clinical use in the late 1950s but fell out of favor by the 1970s. The reason was straightforward: they caused significant kidney damage, and newer, safer antibiotics like aminoglycosides and fluoroquinolones were becoming available.
For roughly three decades, polymyxins sat on the shelf. Then the antibiotic resistance crisis forced them back into service. Bacteria began developing resistance to nearly every modern antibiotic class, including carbapenems, which had been considered the strongest available. Clinicians worldwide found themselves with no other option for treating life-threatening infections caused by these “superbugs.” Despite the known risks, polymyxins were revived as the last line of defense.
What Polymyxins Treat
Polymyxins are FDA-approved for serious infections caused by multidrug-resistant gram-negative bacteria. The three main targets are Pseudomonas aeruginosa, Acinetobacter baumannii, and a family of gut-related bacteria called Enterobacteriaceae. These organisms cause bloodstream infections, urinary tract infections, and meningitis, often in hospitalized or critically ill patients. Polymyxins are particularly important against carbapenem-resistant strains, which the CDC lists among the highest-priority threats to public health.
Beyond these serious systemic infections, Polymyxin B shows up in common over-the-counter products. Combined with bacitracin and neomycin, it’s the active ingredient in triple-antibiotic ointments used for minor cuts and scrapes. It’s also found in prescription ear drops for swimmer’s ear (combined with neomycin and hydrocortisone) and in eye drops for bacterial conjunctivitis (combined with trimethoprim).
An inhaled form is used off-label for people with cystic fibrosis who have chronic lung infections with Pseudomonas aeruginosa. Aerosolized polymyxins have also been used alongside other antibiotics in hospital settings for ventilator-associated pneumonia.
Polymyxin B vs. Colistin
Though Polymyxin B and colistin differ by just a single amino acid in their chemical structure and have identical antibacterial activity in laboratory testing, they behave very differently once administered to a patient. Polymyxin B is given as its active form, meaning it starts working immediately after entering the bloodstream. Colistin, by contrast, is administered as an inactive precursor called colistimethate sodium (CMS). The body must convert CMS into active colistin, and this conversion happens slowly and incompletely.
This distinction matters for how quickly the drug reaches effective levels in the body and how predictable its effects are. Polymyxin B delivers more consistent blood concentrations, while colistin’s reliance on conversion from its inactive form introduces variability. Both carry similar risks of side effects, but the pharmacological differences mean they aren’t simply interchangeable.
Kidney Damage and Other Risks
The side effect that originally drove polymyxins out of clinical practice remains their biggest limitation: kidney damage. A large meta-analysis of critically ill patients found that 34.8% of those treated with polymyxins developed some degree of kidney injury. About one in four cases were mild, while roughly 12.7% were severe.
Several factors increase the risk. Patients over 65, those with sepsis or septic shock, and those with low blood protein levels are more vulnerable. Taking polymyxins alongside certain other medications, particularly vasopressors (drugs that raise blood pressure in critical care) or diuretics, roughly triples the likelihood of kidney problems. Patients who start treatment with healthier kidney function have a meaningfully lower risk.
Nerve-related side effects, including numbness, tingling, dizziness, and muscle weakness, can also occur, though they are less well-quantified than kidney damage. Because of these risks, polymyxins are reserved for infections where no safer alternative exists, and kidney function is closely monitored throughout treatment.
The Growing Threat of Polymyxin Resistance
Because polymyxins are often the only drug that works against the most dangerous resistant bacteria, the emergence of polymyxin resistance is especially alarming. In 2015, researchers in China identified a gene called mcr-1 (mobile colistin resistance) in bacteria from a pig farm. This gene produces an enzyme that modifies the bacterial outer membrane so polymyxins can no longer bind to it effectively.
What makes mcr-1 particularly concerning is how it spreads. Unlike resistance that develops through random mutations within a single bacterial population, mcr-1 sits on a plasmid, a small piece of DNA that bacteria can pass to one another like sharing a file. This means resistance can jump between different bacterial species rapidly. Since 2015, ten different mcr genes and their variants have been identified in bacteria from hospitals, communities, and the environment worldwide.
There is a small silver lining: carrying the mcr-1 gene comes at a biological cost to bacteria, affecting their shape and metabolism. This fitness penalty may slow the spread somewhat, as bacteria must develop additional compensating mutations to survive comfortably with the resistance gene. Still, the global dissemination of mcr genes represents a serious threat to what is, for many patients, the only remaining treatment option.