Lois Rogers

Journalist and Communicator

Could viruses that eat bacteria solve the superbug crisis?

Infection

http://www.dailymail.co.uk/health/article-4790402/Could-gargling-virus-solve-SUPERBUG-CRISIS.html

As she stared down at her husband’s apparently lifeless body, Steffanie Strathdee was forced to contemplate the worst.

Tom Patterson, her husband of 13 years, lay in a deep coma, the victim of an aggressive superbug; it had been more than three months since he’d last spoken.

‘I was told Tom had gone into toxic shock and was on the verge of death,’ she recalls. ‘His heart, lungs and major organs were all shutting down and there was no hope left.’

The couple had been on a Nile cruise to Luxor, Egypt, in November 2015 when one evening Tom, a professor of psychiatry, said he didn’t feel well and went to bed.

‘By the next day he was much worse with bad stomach pain, vomiting, fever and a racing heartbeat,’ Steffanie recalls.

Tom, then 69, and Stephanie, 49, thought he had food poisoning, but at a clinic in Luxor, he was diagnosed with pancreatitis — an inflamed pancreas — and a gastric tube was inserted to rehydrate him and maintain his blood pressure.

When his condition only worsened, Tom was flown to Germany. There, doctors discovered that fluid had collected around his pancreas — and in the fluid, they discovered Acinetobacter baumannii, a bacterium found in soil and water that has started to thrive as antibiotic medicines kill off other bacteria. It is thought the bacterium may have been introduced through the gastric tube.

Tom was immediately put on three different powerful antibiotics — meropenem, tigecycline and colistin — stabilising his condition enough for him to be flown home to San Diego in California.

But the antibiotics were not able to kill off the infection and a month later Tom was still dangerously ill when an internal drain slipped out of place, spilling the deadly bacterium into his bloodstream. Septic shock immediately set in, causing his blood pressure to fall dangerously low, and Tom slipped into a coma. For almost three months he hovered between life and death as intensive care and infectious disease specialists battled to keep him alive.

By March 2016, Steffanie was in despair. ‘He was getting weaker and weaker. I had been told he was going to die. I needed to know if he had run out of fight or if he wanted to carry on.’

As Steffanie held his hand and asked the question, ‘Have you had enough or do you want me to see if I can find some other treatment’, she felt the faintest squeeze of her hand in return.

That set her off on a desperate global quest for a way of fighting the deadly infection. And it was no little thanks to her that Tom is now alive and well.

His apparently miraculous recovery is the result of a natural phenomenon that could not only combat the growth of antibiotic-resistant infections — but also help treat even humble infections such as a sore throat and acne.

The key are viruses known as phages — there are millions of different types of phages all around us which infect and destroy disease-causing bacteria.

As she scoured the medical literature for a treatment, Steffanie, a scientist at the University of California studying the spread of infectious diseases, recalled her school biology lessons about phages.

Phages were used medicinally in the Twenties and Thirties and continue to be used in areas of the world where access to modern antibiotics has been limited.

‘I remembered hearing about a friend of a friend who had been successfully treated with phages for a superbug infection in Tiblisi in Georgia, and I thought that might just be the answer,’ Stephanie told Good Health. ‘It turned out it was the answer. Once Tom got the phage therapy, the transformation was instant. He got better in two days, I couldn’t believe it — nor could his doctors.’

The rise of antibiotic-resistant superbugs is a global crisis which, according to a 2016 UK government review, is responsible for an additional 700,000 deaths a year worldwide from conditions which in the past would have been knocked out by antibiotics — including simple chest infections.

Ironically, the problem was predicted by Alexander Fleming, the Scottish scientist who discovered the first antibiotic penicillin, even as he collected a Nobel prize for his achievement in 1945.

He warned that while easily wiping out susceptible colonies of bacteria and saving millions of lives that would previously have been lost as a result of infected cuts, chest infections or post-operative infections in hospitals, overuse of antibiotics would also clear living space for treatment resistant bugs to flourish and multiply.

In the intervening decades, antibiotics have been freely distributed globally for routine conditions. They have also been used liberally for pets, as well as in agriculture, poultry production and fish farming, often before animals are sick, to protect them from the infections caused by their crowded and unhygienic living conditions.

All of this contributed to a looming crisis. As the UK’s chief medical officer, Dame Sally Davies, warned recently: ‘If we don’t find new treatments, any one of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection that can’t be treated by antibiotics.

‘Routine operations like hip replacements could become deadly because of the risk of infection.’

Phage therapy, which for decades has been repeatedly identified in The Lancet and other leading medical journals as a possible answer to the crisis, could indeed change all that. Tom Patterson received nine different phages following an emergency call to phage researchers by his doctors. Three phages were supplied by Texas A&M (Agricultural and Mechanical) University, and another came from AmpliPhi, a phage research company in San Diego.

These were administered through catheters being used to drain an abcess in his stomach. Five more, given intravenously, were supplied by the Biological Defense Research Directorate of the U.S. Navy Medical Research Centre. There was a potential risk, though rare, of phage therapy itself sending his body into shock. But within two days of receiving the therapy, ‘I was getting better,’ recalls Tom. ‘It was like a miracle.

‘I had no idea how long I’d been unconscious, but if I had been given it when I was first infected I’d have never got sick.’

Although the phages cleared the infection very quickly, it was nine more months before Tom regained strength in his wasted muscles. He finally returned to work earlier this year, over a year after becoming ill, and has just returned home from France, his first foreign holiday since the fateful trip to Egypt in 2015.

Robert Schooley, professor of medicine at the University of California in San Diego, who supervised Tom’s treatment, was amazed by the experiment. ‘Before this, I saw phage therapy as being mainly of historical interest, and of limited use because of the practical and regulatory challenges,’ he said.

‘Now I see them as a very well tolerated and potent antimicrobial tool that can be of clear benefit to patients with multi drug- resistant bacterial infections.’

Indeed the miraculous success of Tom’s phage treatment has triggered interest from microbiologists worldwide. Mzia Kutateladze, director of the Eliava Institute phage therapy treatment centre in Tiblisi, said the number of foreigners coming in for treatment has suddenly risen from 20 per year to 15 or 20 per month, including Britons who pay for their own treatment.

‘We can reduce the bacteria count and improve people’s quality of life,’ she says. ‘We have six different phage products which are approved medicines for a variety of conditions, including chest and stomach infections, but are also working on medicine tailored for individual patients.’

One of her successes is Professor Martha Clokie, an infectious diseases expert at Leicester University who has been working on phages for 17 years and collaborates with the doctors in Tiblisi.

‘About five years ago I had caught tonsillitis in Leicester from my two-year-old son,’ she says. ‘I was in Tiblisi for a meeting and it was getting worse, so they gave me a phage therapy to gargle with to kill the bacteria. It was very yeasty and tasted a bit like Marmite, but it worked.

‘My husband and son had the same infection at the same time. I discovered they had gone to the GP back home and got antibiotics. They both got better at about the same time as me. Not very scientific, but it suggests the phage therapy worked.’

As well as other patients rescued at death’s door by phages, recent reports of successful phage therapy include infected post-surgical wounds, chronic ear infections, antibiotic-resistant acne, and even potentially life-threatening infections in cystic fibrosis patients.

So why isn’t phage treatment being rolled out widely? One problem is that it doesn’t fit European and U.S. methods of trialling and approving medicines. There is also no profit incentive for drug companies in developing them because, as naturally-occurring bacteria-infecting viruses, they cannot be patented.

Professor Clokie, who is now working on phages as a treatment for hospital-acquired infectious superbugs such as MRSA and clostridium difficile, says it is impossible to produce a phage cocktail that contains a precise, measured number of viruses of different types, guaranteed to target a specific infection.

‘If you want to get a product regulated here, you have to know that kind of information,’ she says. ‘It’s very difficult. We had a meeting with the Medicines and Healthcare Products Regulatory Agency a couple of years ago, but we’re no further forward.’

Last week, phage scientists, including observers from the World Health Organisation and some major international drug companies, converged on Olympia, capital of Washington State, for the Evergreen College phage conference, an annual meeting of phage specialists that’s attracted more and more people since it began 22 years ago. One of the promising areas is treating cystic fibrosis.

Jerome Larché, an intensive care specialist in Montpellier, France, reported in 2012 that phage use has controlled lung infection in his brother who is a cystic fibrosis patient and Jane Davies, a professor of paediatric respiratory medicine at the Royal Brompton Hospital, is planning to begin the first human trials of selected phages for cystic fibrosis patients within two years.

A spokesman for the Cystic Fibrosis Trust, which helps to fund Professor Davies’s work, said: ‘We have a strong interest in phage research and hope it leads to a viable treatment for the future.’

As for concerns that phages themselves could trigger illness or overwhelm the immune system, in controlled circumstances the risk of phage use should be minimal, says Professor Davies.

‘Phage treatment should be better than antibiotics because it only targets specific types of bacteria, and not lots of other benefiical or harmless bacteria.’

Studies at the University of Pittsburgh also suggest that phages, given in a cream, can help treat antibiotic-resistant propionibacterium acnes, which cause one in four cases of acne.

In an earlier study at the Royal National Throat, Nose and Ear Hospital in London, 24 patients who’d suffered years of chronic antibiotic resistant ear infections, showed dramatic benefit with phage therapy.

David Harper, an infectious diseases expert involved in the 2009 study, is developing the therapy through his company Evolution Technologies, aiming initially to treat dogs with the same ear infection that humans develop.

‘It is a small market, but if we can get it into commercial use that will prove it is possible to do this,’ said Dr Harper, who is also a member of the Alternatives to Antibiotics panel of advisors assembled by the Department of Health and the Wellcome Trust. ‘We would aim to embark on human trials in about 2022.’

Meanwhile, both the Medical Research Council (MRC) and the Biotechnology and Biosciences Research Council are actively researching phages, and are using insects to test which types of phages can best kill off resistant bacteria. ‘We have a limited pipeline of new antibiotics,’ Dr Jonathan Pearce, head of infections and immunity at the MRC, told Good Health.

‘Bacteriophages which naturally infect and kill bacteria can potentially be used to help eliminate infections.’

Tom Patterson is living proof that they are even now saving people’s lives.

VIRUS TREATMENT IS SENT TO ME IN THE POST

Andy Harper, a 47-year-old businessman from Tunbridge Wells in Kent, says his cystic fibrosis has dramatically improved thanks to phage therapy.

Cystic fibrosis is a genetic condition characterised by a build-up of sticky mucus in the lungs that cannot be cleared — this provides a breeding ground for bacteria: a particular concern is infection with antibiotic resistant strains of pseudomonas aeruginosa bacteria, which can be life-threatening.

Andy contracted pseudomonas in hospital 13 years ago and has had it ever since.

‘The irony is that if it was the normal pseudomonas you find in soil it would probably be treatable,’ he says, ‘but because it is a strain that’s been living in a hospital for the past 30 years, it’s difficult to treat.’

Previously, he’s spent up to two weeks in hospital undergoing regular intravenous antibiotic infusions to try to keep the bacteria at bay. But for the past four years Andy, who is married with no children, has been having treatment from the Eliava Institute phage therapy treatment centre in Tiblisi, Georgia, a public- private partnership.

He sends the clinic sputum samples by post every couple of months. The strains of infection-causing bacteria are analysed and phages to kill them are identified and sent back to him.

‘I originally heard a programme about phage research in Georgia on Radio 4 and decided to get in touch with them,’ he says.

‘They analyse the infection and send back four or five different phages in glass vials which I inhale in a saline solution two to three times a day for two weeks, though sometimes I am directed to drink them in a solution.

‘The first time I got the phages, my chest cleared up within two weeks and I was running around on a squash court again like a maniac.’

Andy says he has not been to hospital since he began the treatment: ‘My GP has been an excellent support for my phage therapy.’

The cost however, is high: Andy pays £400 to £500 a time, but has decided that the treatment is so effective he can stretch to having it up to eight times a year at a cost of up to £4,000.

The Cystic Fibrosis Trust said that although it is helping to fund research into phages, it does not recommend unregulated procedures.

 

Written by Lois Rogers