Ontario scientist thinks old drugs could become our new antibiotics
As the world loses its upper hand in the antibiotic arms race, it raises the spectre of untreatable infections resulting from routine surgeries. But a Canadian scientist has discovered a surprising source of potential antibiotic options.
Over the past few months, there’s been grim evidence of the march to a post-antibiotic world. Last week, for instance, U.S. researchers said they’d identified what could be the first strain of E. coli resistant to antibiotics considered last-line defences.
Antibiotic resistance happens when bacteria change and become able to withstand the antibiotics used to treat the infections they cause. Overuse and misuse of antibiotics increase the development of resistant bacteria, the World Health Organization says.
Superbug headlines like the E. coli one reflect the need to develop new ways to kill bugs that develop resistance to antibiotics.
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That’s where McMaster University scientist Eric Brown’s research comes in.
His team screens thousands of chemicals that are already used to treat other diseases to see if any will work against bacteria.
“We kind of pride ourselves in my research group of doing the crazy stuff. Screens that won’t be done say in a pharmaceutical setting.”
No new antibiotics in years
Since the early 1990s, there’s been little progress in the search for new antibiotics. A new one hasn’t been developed in years, partly because most obvious ones have already been found.
Another big reason is money, according to Dr. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases.
“Antibiotic development is not a big economic profit-making ticket item for pharmaceutical companies because antibiotics, unlike other drugs, are not used by everyone, every day,” Fauci said. “It is unusual for an antibiotic to be a blockbuster.”
Scientists at Brown’s lab take an alternative approach. The challenge is bacteria have multiple layers of defences that scientists need to dismantle.
“It’s sort of like you’re sitting on a four-legged stool, and if you remove one leg, the stool can still function as a stool with three legs,” Brown said. “But if you take away two, you’re going to land on your butt. That’s the sort of synergy we’re looking for in terms of looking for say two compounds that will act against a bacterial pathogen.”
He’s made some surprising discoveries: antidiarrheal medication modium and anticonvulsant drug lamotrigine also seem to kill bacteria.
‘It’s getting worse’
Fortunately at this point, not every microbe can resist every drug. The concern is how many resistance genes float around for bacteria to swap, giving them the ability to disarm drugs. It means that if someone is infected with one, doctors are forced to try alternatives, no matter how toxic or expensive, to see if anything works.
Fauci says Canadians and Americans may not appreciate the seriousness of microbes with resistance to multiple antibiotics.
“It’s worse and it’s getting worse,” Fauci said. “That is one of the things we are concerned about.”
Former NFL star Daniel Fells is a case in point. Fells got a superbug infection in his foot after a simple injection of cortisone for an injured ankle. After almost a dozen surgeries to remove the infected tissue, the superbug ended his football career.
It’s a sign of how routine medical care is getting increasingly complicated as we try to stay a step ahead of the microbes.
Minor surgeries are already becoming more dangerous. Last year, researchers writing in The Lancet Infectious Diseases warned that between 39 and 50 per cent of bugs that cause infections in surgical sites are already resistant to standard antibiotics.
Chemotherapy will also be increasingly risky, the authors said. More than a quarter of pathogens that cause chemo-related infections are resistant.
Sense of urgency
The findings add a sense of urgency to Brown’s work in Hamilton, Ont.
“Think about just about any inpatient surgery that you can imagine. Something we take so for granted like a caesarean section. The risk of infection would suddenly go through the roof as a result of not having antibiotics to treat infection,” Brown said.
The advantage of repurposing old drugs to fight bacteria is they’ve already been tested and proven to be safe.
The pharmaceutical industry typically takes 15 years to develop a drug.
“I think though that we’ve got a chance to shorten the path to the clinic by starting with a lead that is already a drug,” Brown said.
They still need to be modified and tested as antibiotics, but in the face of growing resistance, repurposing could be part of the multifaceted solution, Fauci says, alongside more judicious use.