Reuse your... antibiotics? Canadian scientists are breathing new life into existing infection fighters.
Resistance to many of these currently available drugs, they say, is a ubiquitous and relentless clinical problem compounded by a dearth of new therapeutic agents.
But by combining them with other drugs – nonantibiotic drugs – the researchers have identified new ways to kill unwanted microbes, offering “an opportunity to sample a previously untapped expanse of bioactive chemical space,” the authors write.
The team, led by Eric Brown and Gerard Wright of McMaster University, tested combinations of antibiotics with known drugs used to treat Parkinson’s disease, cancer, and inflammatory diseases.
For decades, obvious efforts to combine antibiotics to increase their efficacy against resistant bacteria don't go far enough, says Wright. Only considering other antibiotics is too limiting: "You need to cast the net a bit wider and look at other molecules that are bioactive."
- They identified several cases where a nonantibiotic drug weakens bacterial cells, making the bacteria vulnerable to the proven antibiotics.
Focusing on minocycline (pictured) – an antibiotic frequently used in the 1950s and 60s until bacteria developed resistance – they screened it in combination with more than 1,000 previously approved bioactive drug compounds.
The Scientist explains the unexpected interactions:
The screen revealed a total of 69 compounds never before used to treat bacterial infections that, when combined with minocycline, decreased bacterial growth by at least 45% – significantly more than when treated with only the antibiotic.
“These combinations might be a way to selectively target bacteria and combat disease and leave so-called ‘good bacteria’ intact to do other things,” Wright says. “In effect you use fewer antibiotics to get the same effect."
In one creative combination, the over-the-counter loperamide – sold as Imodium to treat diarrhea – can make bacterial cells sensitive to a variety of antibiotics like minocycline. This could one day help patients with cystic fibrosis, the world’s most common hereditary lung disease.
"Previous advances in treating cystic fibrosis have been in managing infection,” says Brown, “but since infectious organisms are increasingly developing resistance to antibiotics, the importance of providing new treatments is more important than ever."
It typically takes 13 to 15 years to develop a drug, but according to Brown, this approach could cut drug development time in half.
The study was published in Nature Chemical Biology yesterday.