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An incredibly ill teenage girl with a super infection with an antibiotic-resistant bacteria has seen her life saved by an ingenious treatment designed specifically for her.
Creating a cocktail of hungry bacteria viruses, genetically engineered to hunt at best, an international team of doctors and microbiologists have not only extended their lives, but they have also achieved a medical first by drawing attention to a long-lasting treatment neglected in the West.
Isabelle Carnell-Holdaway, now 17, was diagnosed with cystic fibrosis when she was a baby. She is struggling with a bacterium infection superbly re-emerged for 8 years.
During her youth, the Mycobacterium Abcessus the infection – related to tuberculosis and leprosy – was cleared up, but a few years ago, after having undergone a double lung transplant, everything came back in force.
Insensitive to hospital antibiotics, Carnell-Holdaway's liver and lungs quickly began to fail, and his chances of survival quickly dropped below the 1% mark. In an ultimate attempt, his mother suggested something unconventional: what about phage therapy?
Bacteriophages are named viruses and recognized for their ability to devour superbugs such as Carnell-Holdaway, though never specifically. this a.
Discovered in the late 1800s, they have been used for over a hundred years in the Soviet Union and Eastern Europe to successfully treat a range of bacterial infections, including dysentery, tuberculosis, salmonella, E. coliand staphylococcus
In a Polish newspaper, where antibiotics were ineffective for almost all 550 patients, phage therapy was more than 90% effective.
The mother of Carnell-Holdaway wanted to know if something similar could be done for her daughter, but in the UK, the experimental treatment remains controversial and little studied.
Besides the success of antibiotics, one of the reasons why the West has largely ignored these encouraging results is that many studies, including the one mentioned above, do not include control groups . Research also tends to be written in languages other than English.
"Isabelle's parents knew we were trying to work on this phage therapy so when the time came, we had no more other conventional therapies to use and signs of infection. They were desperate for other options, "said Helen Spencer, lead author and physician, L & # 39; Independent.
There was every reason to try, especially since doctors in San Diego had recently used phages to successfully treat a multidrug-resistant human bacteria called Acinetobacter baumannii.
The University of Pittsburgh is home to the largest collection of bacteriophages in the world, which seemed like a good starting point. The curator of this collection of 15,000 flasks, the microbiologist Graham Hatfull, was nervous but more than happy to oblige. And so, his team spent months researching the perfect phages to fight the Carnell-Holdaway infection.
Hatfull has lingered over three viruses in particular. A virus, called "Muddy", came from a decaying eggplant. It was therefore a killer born from birth. The other two, named ZoeJ and BP, needed a little more encouragement.
In fact, this sleepy behavior is one of the problems that slows down phage therapy. Many of these viruses are simply not deadly enough to be effective as treatments, and when their reach is so specific, they become almost useless.
"I had the impression that this collection was extremely powerful to answer all kinds of biology questions," said Hatfull. "But we did not think we would ever be able to use these phages therapeutically."
The key could be a bit of genetic tweaking. In this case, ZoeJ and Bps have had a particular gene removed, which causes them to curl up and fall asleep once they have entered a bacterial cell. Without this peaceful burden, the phages were no longer so merciful and reproduced repeatedly until their offspring finally emerged from the host cell and destroyed it.
"Antibiotics are very effective, but they are blunt instruments," said Hatfull. L & # 39; Independent.
"With phage, it's the opposite end of the spectrum.They are very specific, it's a targeted strike, you're not going to affect the rest of the microbiome and they're low-toxic because they do not infect human cells. "
After purifying the phages, testing them safely and mixing them to create a stronger forehead, the new drug was ready. In June 2018, Carnell-Holdaway received a twice daily intravenous injection of this viral cocktail containing one billion particles of phage in each dose.
Six weeks later, the infection had virtually disappeared from his liver and there remained only one or two cutaneous nodules.
Although the patient was not completely cured of the superbugs infection, she resumed all her normal activities and the bacterium has so far shown no resistance to treatment. Moreover, even if they do, researchers will soon be ready to add a fourth phage to the mix.
"It's actually a historic moment," said PPR expert Steffanie Strathdee, a phage expert and doctor who worked on previous research in San Diego.
"This is the first time a genetically modified phage has been used to successfully treat superbug in humans," says Strathdee. "It's terribly exciting."
In the published case study, the authors argue that, in the face of growing resistance to antibiotics, further therapy with genetically modified phage treatment could possibly save even more lives.
"The phage therapy seems to be [the] the most promising alternative to antibiotics, "added Strathdee.
This study was published in Nature Medicine.
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