It was by chance that McMaster University professor Eric Brown found a possible solution to the growing problem of antibiotic resistance: bicarbonate.
Now, helped by $300,000 from the seed fund sponsored by McMaster’s vice-president, research, his start-up firm Synmedix will soon test a new topical preparation of bicarbonate mixed with the antibiotic azithromycin to treat infected diabetic foot ulcers (DFUs).
This potentially game-changing solution is called BCX and, if successful, could both combat drug-resistant bacteria and help develop a thriving biotech sector in Hamilton.
“It is crazy because it is so simple,” said Brown, a Distinguished University Professor of biochemistry and biomedical sciences at McMaster and a member of Canada’s Global Nexus for Pandemics and Biological Threats as well as the Michael G. DeGroote Institute for Infectious Disease Research.
“The epiphany came when we were doing animal studies of infections and treatments and there were some compounds that worked much better in animals than on a petri dish, so we tried to figure out what the magic ingredient was. It turned out bicarbonate was the key.”
Brown said there are currently no topical antibiotics that can treat diabetic foot ulcers, which every year affect 140 million people with diabetes worldwide. Of these patients, half will suffer a diabetic foot ulcer infection, which is often difficult to treat with oral antibiotics, owing, in part, to drug-resistant bacteria.
He said that bicarbonate’s effectiveness could be explained by the role it plays in helping the immune system fight off harmful bacteria and other pathogens.
While this is still “just a hypothesis,” as Brown put it, bicarbonate could nonetheless be a key ingredient in the development of new antibiotics to combat drug-resistant bacteria.
He said that adding bicarbonate both improves the uptake of azithromycin into infected cells and expands the activity of many drugs against both gram-negative and gram-positive pathogens. A bacterium is defined as either gram-negative or positive depending on if they appear purple under a microscope when coloured with crystal violet during gram-stain tests.
Secondly, the ability of bicarbonate ions to drive increased uptake of drugs by infected cells overcomes both the intrinsic and acquired form of drug resistance in bacteria, Brown said.
“The next stage for BCX is trials in humans, which we can fast track as azithromycin is already being used and bicarbonate is so benign,” said Brown.
“The two components of this therapy have a long history of use by humans, so the regulatory hurdles are low, but what remains to be proven is whether or not it works.”
Researcher Maya Farha, who discovered BCX’s effectiveness in Brown’s lab, said she mixed bicarbonate with several antibiotics and found that azithromycin responded best.
Farha said that BCX also has potential as a topical solution to treat infected burns and the military have already expressed interest. She said an effective battlefield solution applied on burns before injured soldiers reach hospital could save many lives.
She said that BCX could in future be turned into an aerosol spray to combat chronic lung infections that are often a complication of cystic fibrosis. Another potential target for an aerosol treatment is tuberculosis (TB) – a textbook example of antibiotic resistance for many clinicians. Currently, TB infections require months-long courses of multiple oral antibiotics to achieve a cure.
“BCX has great potential, and it could be a game-changer in the field of antibiotic development and infectious disease research,” said Farha.