Closantel and Antibiotic Resistance: How a Sheep Dewormer Could Fight Superbugs
There’s a drug sitting in barns across the world that most human doctors have never heard of. It’s used to treat liver flukes in cattle and sheep, and it’s been around for decades. But researchers are now looking at this same drug—closantel—and wondering if it might help us fight one of the biggest threats to human health: antibiotic-resistant bacteria.
The Problem Nobody Wants to Talk About
Let me be direct: we’re losing the war against superbugs. The World Health Organization projects that antibiotic resistance could cause 10 million deaths every year by 2050. That number is staggering, and it’s not science fiction—it’s a conservative estimate based on current trends.
Gram-negative bacteria have become particularly stubborn. Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae—these names sound like alphabet soup, but for doctors treating infected patients, they’re nightmares. These bugs have developed resistance to nearly every antibiotic we have. When all else fails, physicians reach for colistin, an old drug from the 1940s that was largely abandoned for decades because of its toxicity. Colistin became the last line of defense.
Now even colistin is starting to fail.
Here’s what makes this crisis different from previous public health emergencies: pharmaceutical companies have largely stopped trying to develop new antibiotics. The economics don’t add up. A company might spend a billion dollars and ten years developing a new antibiotic, only to have bacteria develop resistance to it within a few years of its release. Antibiotics simply don’t generate the ongoing revenue that drugs for chronic conditions do.
We’re running out of options, and we need to think differently about the problem.
A Question Nobody Was Asking
Scientists at Monash University in Australia and the University of Manitoba in Canada started asking a question that seemed almost too simple: instead of finding new antibiotics from scratch, what if we could make our existing antibiotics work again?
They weren’t thinking about new molecules or novel drug targets. They were thinking about drug repurposing—taking drugs we already understand and finding new uses for them.
The Monash team focused on a group of compounds called salicylanilides. These are antiparasitic drugs that have been used in veterinary medicine for years. Closantel is one of them. So are oxyclozanide and rafoxanide. Farmers use these drugs to deworm livestock, particularly for liver fluke infections. The mechanism is straightforward: these compounds uncouple oxidative phosphorylation in parasites, essentially short-circuiting their energy production.
But here’s what got interesting. When researchers tested closantel by itself against Acinetobacter baumannii, the results were underwhelming. At 16 mg/L, the drug showed barely any antibacterial activity. This made sense—it was designed to kill parasites, not bacteria.
But then they tried something different.
The Combination That Made Scientists Take Notice
They combined closantel with polymyxin B, which is closely related to colistin. The results were striking.
When used together, the two drugs didn’t just work better—they worked against strains that were completely resistant to polymyxins alone. This wasn’t a minor improvement. This was a complete reversal of resistance in some cases.
The numbers tell the story. Concentrations of closantel between 4 and 16 mg/L were sufficient to restore polymyxin sensitivity in resistant strains. More importantly, the combination prevented resistant strains from developing in the first place when exposed to sublethal antibiotic concentrations.
The mechanism appears to work through multiple pathways. First, as an oxidative phosphorylation uncoupler, closantel disrupts bacterial energy metabolism. This weakens the bacteria’s membranes, making them more vulnerable to polymyxin attack. Second, salicylanilides appear to interfere with bacterial two-component regulatory systems—the molecular machinery bacteria use to detect and respond to threats like antibiotics.
Researchers at the University of Manitoba expanded on this work in 2019, testing combinations of all three salicylanilides with colistin against a broader range of resistant bacteria. The results held up across multiple species: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. In every case, adding a small amount of salicylanilide restored colistin’s effectiveness against resistant strains.
Why This Approach Makes Sense
I want to be careful here because I’ve seen too many breathless announcements about breakthrough treatments that never materialized. But there’s something genuinely interesting about this approach.
First, we’re not starting from scratch. These drugs have been used in animals for years. We know something about their safety profiles. That’s not nothing—developing a completely new antibiotic requires establishing safety from scratch, which takes time and money.
Second, the concentrations needed for synergy appear achievable in human blood. The 4-16 mg/L range used in the studies is within the range that might be reachable with appropriate dosing, though this needs to be confirmed in clinical trials.
Third, the approach is clever. Instead of trying to kill bacteria directly with new compounds, we’re making our existing last-resort antibiotics work again. We’re essentially buying time with drugs we already have while the search for new solutions continues.
What We Don’t Know
I should be upfront about the gaps in our knowledge.
No human clinical trials have been conducted. Everything I’ve described took place in laboratory settings—in vitro, as scientists say. How findings in a petri dish translate to actual human infections is never straightforward. Bacteria behave differently in the complex environment of a human body, surrounded by immune cells and competing microbes.
The exact mechanism of synergy isn’t fully understood. Researchers have identified plausible explanations—membrane disruption, interference with regulatory systems—but the precise molecular interactions need more study.
There’s also the question of whether bacteria will simply adapt to these combinations given enough time. Evolution is relentless. Given strong enough selective pressure, bacteria tend to find ways around our interventions. Laboratory studies showed no resistance emerging during the observation periods, but those periods were relatively short.
Finally, there’s the regulatory maze. Getting a veterinary drug approved for human use—even for a life-threatening condition—isn’t a quick process. It requires extensive safety data, clinical trials, and regulatory approval from multiple agencies. The path from laboratory finding to bedside treatment is long and expensive.
The Bigger Picture
Closantel isn’t the only example of drug repurposing in the antibiotic resistance fight. Researchers are screening thousands of existing compounds for potential antibiotic-enhancing effects. Some are looking at psychiatric drugs. Others are examining compounds originally developed for cancer treatment. The diversity of approaches is encouraging.
But closantel stands out for a few reasons. Its veterinary track record suggests it has a reasonable safety profile. The mechanism of synergy appears to target resistance mechanisms rather than the bacteria directly, which might make it harder for resistance to develop. And the global spread of plasmid-mediated colistin resistance genes—like mcr-1—creates urgency around finding solutions.
Looking Ahead
I keep coming back to the story of this obscure barnyard drug. Closantel has been quietly deworming sheep for decades while the antibiotic crisis built to its current crisis point. Nobody connected these two worlds until researchers decided to ask an unconventional question.
That’s often how breakthrough ideas work. The solution isn’t always hiding in a new molecule or a cutting-edge technology. Sometimes it’s sitting in a barn somewhere, waiting for someone to look at it differently.
Closantel may never make it to human clinical use. The path from laboratory to pharmacy is full of failures. But the science is compelling enough that researchers are paying attention, and the need is urgent enough that they keep looking.
Sometimes the answer to our biggest problems has been there all along, hiding in plain sight. We just had to know what question to ask.
FAQ
What exactly is closantel? Closantel is a salicylanilide compound used in veterinary medicine to treat liver fluke infections in cattle, sheep, and other livestock. It works by disrupting energy production in parasites.
How could a sheep dewormer help with antibiotic resistance? Researchers discovered that closantel can boost the effectiveness of colistin-type antibiotics against drug-resistant bacteria. When combined, the drugs overcome resistance mechanisms that would otherwise make treatment impossible.
What is drug repurposing? Drug repurposing means finding new uses for existing drugs. Since these drugs already have established safety profiles, the development process can be faster than creating entirely new medications from scratch.
Which bacteria are affected? The combinations have shown effectiveness against several dangerous Gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, and Enterobacter cloacae.
Is closantel approved for human use? No. Closantel is currently only approved for veterinary applications. Human clinical trials would be needed before it could be used in medical settings.
When might this treatment be available? It’s too early to say. The research so far has only been conducted in laboratories. Years of additional studies—including animal testing and human clinical trials—would be required before any potential approval.
Why is colistin resistance so concerning? Colistin is a last-resort antibiotic for treating multidrug-resistant infections. When bacteria resist colistin, doctors often have few alternatives. The spread of resistance genes like mcr-1 through bacterial populations has made this an urgent global health issue.
Could bacteria become resistant to this combination? Laboratory studies didn’t show resistance emerging during the observation periods, but bacteria eventually adapt to most antibiotics. Long-term durability remains unknown.
