Researchers transform old drug into new fighter against antibiotic resistance
Pentamidine makes antibiotics effective when combined, McMaster University researcher says
Scientists have been losing their upper hand in the antibiotic arms race against infectious disease for years. But a group of researchers at McMaster University claim they've discovered a new fighter against drug resistance in a surprising source.
An existing anti-fungal drug — pentamidine — commonly used to treat pneumonia and HIV is believed to offer a solution against these superbugs, when taken in combination with antibiotics.
"What we're talking about now is a molecule that's already a drug that can make a number of antibiotics, that are formerly not useful for the treatment of gram-negative bacteria, capable of treating this class of organisms," said Eric Brown, lead researcher on the trial and a professor of biochemistry and biomedical science at McMaster's Mchael G. DeGroote School of Medicine.
Misuse impacts resistance, WHO says
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.
Targeting antibiotic resistant bacteria
A cluster of bacteria, called gram-negative bacteria developed an ingenious system to protect themselves against any molecule that might kill them.
They have two cellular walls, making it harder for drugs to penetrate the double exterior membranes, and are equipped with pumps and other tools to reject drug molecules, Brown explained.
This drug-resistant bacteria blocks out all antibiotics, including last resort drugs.
'This is an existing drug'
Four years ago, Brown took an alternative approach, by focusing on dismantling this bacteria's most challenging aspect.
"Our strategy was to target that outer membrane and find ways to disrupt it," he told CBC News.
'What we're talking about now is a molecule that's already a drug that can make a number of antibiotics, that are formerly not useful for the treatment of gram-negative bacteria, capable of treating this class of organisms.' - Eric Brown, microbiologist
Modern technology enabled these researchers to screen more than 500,000 compounds from nearly 2,000 off-patent drugs, giving them the tools to uncover the pentamidine compound and test its effectiveness when combined with antibiotics in mice.
"It's pretty interesting to me that this is an existing drug," Brown said.
"Most of the stuff that goes on in my lab is pretty far from the clinic, in terms of the discoveries we make and the kind of science that we do. But the fact that a known drug can do this so effectively I think is pretty exciting in terms of the prospect to move this more quickly into the clinic."
The shortcomings of pentamidine
But Brown explained this isn't a catch-all solution.
Research uncovered that the pentamidine cocktail was only effective in Acinetobacter baumannii and enterobacteriaceae bacteria.
It didn't have the same success in Pseudomonas aeruginosa because "the outer membrane is somehow subtly different."
"The composition of these membranes isn't identical and we think that might be at the root of the differences that we saw," he added.
Pentamidine also has some "shortcomings with long-term use."
"There are some known toxicities for pentamidine," he stated.
These side-effects include liver and kidney damage, which are typically seen in patients who take the drug for three weeks or more.
Brown says he hopes to address this in future research.
"We wonder if we can come up with a better pentamidine, with subtle changes to the structure of that compound," he said.