First Canadian trial successfully uses phage therapy to stop life-threatening UTI caused by superbug

The first Canadian study using phages to treat superbug infections is underway with scientists reporting a preliminary but encouraging early success case.

"You are considered clinically and biologically cured," said Victoria Marshall as she read a text message from her doctor on the latest test results.

It brought her to tears.

"Well, I can have my life back. It's been really hard."

The 72-year-old retired librarian began suffering from urinary infections when she was 65. It's one of the most common infections in the world affecting about one in four women over their lifetime. Marshall suffered from pain and with a nearly constant burning sensation that had her running to the nearest bathroom.

"There'd be very sharp burning almost all of the time, urgency and occasional dampness," she told CTV News. "I couldn't go out of the house for more than an hour at a time, without knowing where a bathroom was."

But her UTI could not be killed off by any of the half-a-dozen antibiotics prescribed to her.

It was a treatment-resistant e-coli infection, also known as a superbug infection. Even powerful drugs delivered by IV couldn't eliminate the bacteria and caused her side effects like nausea and body pain.

• COVID-19 Brief newsletter: Sign up for an informed guide on the pandemic

Without an effective way to stop it, the infection travelled up her urinary tract to one of her kidneys which had to be removed. Victoria feared the other would be at risk, too.

"By the end, it was like, well, we've run out of options. There wasn't anything else. It's scary,” she told CTV News.

In May, Marshall became patient number one in the first Canadian study using phages for treatment-resistant UTIs led by Dr. Greg German, an infectious disease physician at St. Joseph's Hospital, part of Unity Health in Toronto.

He had long been intrigued by phages as a potential tool in the fight against the growing spectre of antibiotic-resistant infections.

"(Phages) shoot to kill and they ... have a natural ability to go to the source, make more of itself, and continue to be there while the infection is still there," said Dr. German.

SMART BOMBS

Phages exist everywhere bacteria is found -- in water, soil, and sewage, and they act like viral smart bombs. They target bacteria and inject their DNA to produce more phages until the bacteria explode, expelling billions more phages that search for new targets.

The clinical trial used three strains of phages which were selected because they targeted Marshall's strain of e-coli infection. They were collected and purified in a lab at Baylor College of Medicine in Houston, Texas, where they are also studying phages for UTIs.

It is a form of personalized medicine, says Dr. German. "They're all targeted against E. coli ... drug-resistant E. coli that we couldn't get rid of any other way. Unless they were on daily IV antibiotics. And that's not a long-term solution," he added.

Phage therapy isn't currently available in Canada, but it was a French Canadian scientist, Felix d'Herelle, who co-discovered it in 1917.

Billions of phages were infused into Marshall's bladder, sponged onto her vaginal area and Marshall even drank some of them, to deliver them into her urinary tract. Compared to weeks of antibiotic therapy, she calls phages her "one-shot treatment."

"I started to feel better within about 48 hours,” said Marshall.

• Sublingual vaccine for urinary tract infections is awaiting approval by Health Canada

When doctors saw bacteria levels start to rise again shortly after the treatment, they administered a mild antibiotic that had not worked before. Doctors suspect phages may make treatment-resistant bacteria more vulnerable to standard antibiotics.

"I've been feeling like a new woman," said Marshall, whose confirmed tests show that a month later she continues to be infection free. Before phage therapy, Dr. German says they would see a return of Marshall's infection within a matter of days.

From left: Jiten Jain, pharmacy manager at St. Joseph's Health Centre; Victoria Marshall, research patient; and Dr. Greg German, chronic infection clinic physician (Photo supplied by Dr. Greg German)

"We're excited about the progress so far. And we're looking to see how the data comes together and we get information from our collaborators to show that the infection is truly gone," he said, adding that the research is in the early stages.

He presented Marshall's case at a meeting of phage scientist’s Viruses of Microbes meeting underway in Tbilisi, Georgia.

"I'm very excited to see that this is moving forward in Canada, it's high time," said Steffanie Strathdee. She heads the Centre for Innovative Phage Applications and Therapeutics (IPATH) at the University of California at San Diego.

Strathdee, a Canadian scientist, also harnessed the power of phages to save her husband, Tom Patterson, from a nearly fatal superbug infection, documented in her book "The Perfect Predator"  and featured in a CTVW5 documentary.

• A long forgotten Canadian discovery used to treat superbugs

IPATH also connects patients suffering from treatment-resistant infections and their doctors, with scientists collecting phage. The group has already treated dozens of people and is consulting on many international cases including people with respiratory infections and people with hip or knee replacements that have led to hard-to-treat infections.

CANADIANS INTERESTED IN THE THERAPY

Dr. German says he is also getting calls from Canadians with superbug infections, who want to try phage therapy.

While they are available on compassionate grounds in the U.S. and in parts of Europe, Canadian regulators require a formal clinical trial to determine safety. That's why he says his phase one study is so important. He will now test 200 more women with treatment-resistant urinary tract infections in Ontario to start, hoping to have results on phage safety for Health Canada within two years.

"Everything we have seen in our global experience with phage therapy is indicated that it's safe and it's ready to move forward to the next step," said Strathdee.

• Sign up for The Informant for insider-only information on W5 investigations

Marshall, meanwhile, is keeping a diary of her symptoms and any side effects, of which she says there was only temporary fatigue. She is not only sold on phages, even at this early stage, she's also an advocate for women like her who are suffering with no solutions.

"I’d like to tell people not to be afraid of it. It's easy. minimal side effects. Great outcome." she said.

CANADIAN DISCOVERY

Phage therapy may not be available in Canada but it did start here over 100 years ago.

French Canadian scientist Felix d’Herelle co-discovered these micro killers in 1917. Early studies showed they were very good at controlling outbreaks of dysentery and typhoid plague.

But phages were abandoned in favor of antibiotics, which could be mass-produced and were much more profitable. Eventually, D'Herelle moved to the Soviet Union to continue his work. And phages were relegated to the fringes of mainstream medicine.

Over the years, bacteria evolved and now many are resistant to our antibiotic wonder drugs. Patients around the world are developing treatment-resistant infections after joint replacements, organ transplants, and cancer therapy.

A recent report predicts superbugs will claim the lives of almost 400,000 Canadians in the next 30 years.

And the World Health Organization is warning we are entering a post-antibiotic age – where even a simple skin infection can kill.

NOTE:

Although men also contract UTIs, they are far more common among women and other people with vaginas, partly due to a shorter urethra, which makes it easier for bacteria to enter the urinary tract.

• More medical news on CTVNews.ca

You can watch Avis Favaro's report on CTV National News, and her documentary 'Super Bug Killers' that aired on CTVW5, both in our video player at the top of this article.