Tag Archives: bacteriophage-=based antibacterial therapy

Running Out of Options; Bacteriophages to Treat Antibiotic Resistance Infections

Ella Balasa, a 26-year-old from Richmond, Virginia, recently made the news when she was apparently successfully treated for a lung infection using a kind of virus called a bacteriophage. The word “apparently” is important in terms of determining exactly how effective the treatment was, in a clinical sense.

A bacteriophage is a virus that infects bacteria. They aren’t typically used to treat bacterial infections, but in desperate cases, they have been used to treat particularly antibiotic-resistant infections. Such as the one that Balasa was battling.

“I’m really running out of options,” Balasa told AP. “I know it might not have an effect. But I am very hopeful.”

Balasa has cystic fibrosis, which is a disease that affects the lungs, scarring lung tissue, which can trap bacteria. She had picked up an antibiotic-resistant strain of Pseudomonas aeruginosa. At first, inhaled antibiotics controlled the infection, but then they stopped working. She was placed on intravenous antibiotics, but Balasa didn’t respond to those either.

Balasa took part in a procedure at Yale University that used bacteriophages that attack and kill P. aeruginosa. It was a last-ditch effort to avoid a high-risk lung transplant. She was the eighth patient to try the approach.

The first test case at Yale was an 82-year-old man who was close to death from a heart implant and untreatable pseudomonas infection. Benjamin Chan, a Yale biologist who focuses on phages, purified a phage found in a Connecticut lake that he matched to the patient’s strain of bacteria. With emergency permission from the U.S. Food and Drug Administration (FDA), physicians tried the purified phage on the man’s infection—successfully. The infection cleared up.

“People’s frustration with antibiotic resistance boiled over,” Chan told. “We’re more appreciative of the fact that we need alternatives.”

Bacteriophages were discovered independently by Frederick Twort in 1915 and Felix d’Herelle in 1917—a full decade before the discovery of penicillin. At that time, they were used to treat dysentery and cholera. But timing is important, and not much was known about viruses and phages at the time—it would be another 25 years, in 1940, before an image of a phage was made using an electron microscope.

And unlike broad-screen antibiotics, strains of phage are specific to strains of bacteria. A broad-screen antibiotic can be used to treat a range of bacterial infections, but phages need to be chosen and purified specific to the infecting bacteria.

On the other hand, as antibiotic-resistance becomes a bigger issue and development of new antibiotics is slow, attention is turning toward the possibilities of phages to treat antibiotic-resistant bacteria. A 2017 article by Veerasak Srisuknimit on the Harvard University blog, wrote, “Now that more and more bacteria have developed resistance to antibiotics, scientists around the world have a renewed interest in phages. The European Union invested 5 million euros in Phagoburn, a project that studies the use of phages to prevent skin infections in burn victims. In the USA, the FDA approved ListShield, a food addictive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis. Currently, many clinical trials using phage to treat or prevent bacterial infections such as tuberculosis and MRSA are undergoing.”

And Balasa? She inhaled billions of phages over seven days. It appeared to have an almost immediate effect, although it took several weeks for her to feel better. And during that period she began retaking some antibiotics she had abandoned. As AP notes, without a formal study it’s hard to say just how successful the approach was, but the tests “suggest phages killed much of her predominant pseudomonas strain and made the survivors sensitive again to a course of those antibiotics.”

She was able to quit the antibiotics, but a second round of a different strain of phages did not seem to show more improvement. “The true test,” Balasa told AP, “is how long I can go without using any antibiotics again.”

By Mark Terry

 

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https://www.pharmalive.com/bacteriophages-to-the-rescue-a-possible-approach-to-antibiotic-resistance/

University of Leicester Researchers Identified the Potential Of Using A Bacteriophage Cocktail To Eradicate C. difficile Infection (CDI)

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University of Leicester scientists have previously identified the potential of using a bacteriophage cocktail to eradicate Clostridium difficile infection (CDI)

 

and in this research, using an insect model, they show that their prophylactic use can prevent infection forming in the first place.

The data, which is the result of research conducted by University of Leicester researchers Dr. Janet Nale, and Professor Martha Clokie, both from the Department of Infection, Immunity and Inflammation, demonstrated that C. difficile phages are particularly effective when used to prevent infection, but they are also good at targeting harmful bacterial infections once biofilms have formed.

Using biofilm and waxworms as models, these phages reduced C. difficile bacterial counts when administered as a preventative measure. Furthermore, combinations of phages and vancomycin led to a marked decrease in C. difficile colonization in the waxworms.

The fact that this was an experimental lab study in waxworms means that conclusions can be made about cause and effect in this species.

Phages have not been used in humans to treat CDI and to see whether these results apply to people, an experimental trial with people would be necessary. However, work with insect models is crucial to our understanding of how best to exploit them. They have shown that these new models are useful tools in which to investigate the timings and dose regimens of phage treatment.

The paper is now published online and is expected to be published in a hard copy special issue of Frontiers in Microbiology.

The study was funded by AmpliPhi Biosciences Corporation, a developer of bacteriophage-based antibacterial therapies to treat drug-resistant infections.

Professor Martha Clokie has been investigating an alternative approach to antibiotics, which utilises naturally occurring viruses called bacteriophages, meaning ‘eaters of bacteria’, for nearly a decade at Leicester.

She said: “The results suggest that it may be possible to reduce the threat of C. difficile, and potentially other bacterial infections, through the use of phages both prophylactically to prevent infection, and as therapy once an infection is established. Phage therapy targets specific pathogenic bacterial populations while sparing patients’ beneficial microbiome.”

M. Scott Salka, CEO of AmpliPhi Biosciences, said: “The data support our products’ great potential in addressing antibiotic resistant and difficult to treat infections, including C. difficile. I would like to commend Dr. Nale and Professor Clokie for their exciting and insightful research demonstrating the immense promise of phage therapeutics. Their findings underscore our enthusiasm for the potential of our proprietary platform to enable the development of therapeutics to treat a broad range of bacterial infections that are resistant or have suboptimal responses to current antibiotic therapies.”

 

Source:

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01383/full