A persistent infection in a pet cat’s leg after a compound fracture was repaired has finally been cured using cutting-edge experimental medicine: personalized bacteriophage therapy.
What do you think of when you hear the word “virus”? Perhaps the common cold, or the “bird flu” virus, which is making headlines daily, or perhaps the global coronavirus pandemic that we are living in right now.
Although viruses can be found in every ecosystem on the planet, and can infect every species alive, most people think of them as solely causing deadly infections. So it may surprise you to learn that there are some viruses — an entire of group of viruses in fact, that may be beneficial to us. These viruses, known as bacteriophage, or simply as “phage,” are viruses that infect and replicate only within bacteria and archaea.
The enemy of my enemy is my friend
Bacteriophages are amongst the most common and diverse entities in the biosphere. They once were commonly used as medicine — to treat bacterial infections in people residing in the former Soviet Union, France and parts of Eastern Europe during the 1920s and 1930s until the discovery of antibiotics displaced them from pharmacy shelves. Because antibiotics are so widely abused today — by the livestock industry in particular — bacteria have had plenty of opportunities to learn how to resist these drugs and they quickly shared their abilities widely with other, naive, bacteria. Some bacteria collected antibiotic resistant methods rather like some people collect books, and now, bacteria are popping up that can resist every antibiotic and chemotherapy available.
These bacteria infect people, their livestock and even their pets. But recently, steps have been taken to discover and to harness the deadly capabilities of bacteriophages to selectively target, infect and kill deadly drug-resistant bacterial infections in people (read more here). Thus, phages are considered to have a high therapeutic potential for the treatment of severe bacterial infections, especially those that cannot be treated with antibiotics.
Now, a new study reports that a 5-year-old Siamese cat named Squeaks has also benefitted. The pet cat was successfully treated with personalized bacteriophage therapy after becoming infected with a multidrug-resistant strain of the bacteria, Pseudomonas aeruginosa. This bacteria is extremely versatile, also infect humans and most other animals — and even plants — making it extremely challenging to successfully treat in modern medicine.
This is the first time that phage therapy has been successfully used to treat a sick animal.
Squeaks was initially brought to Kiryat Anavim veterinary hospital after falling three stories out of a window. The cat suffered multiple fractures in both hind legs and damage to her surrounding soft tissues that required multiple surgeries to repair.
Tragically, two weeks after surgery, tissue necrosis set in, leading to the amputation of Squeaks’ left hind leg, whilst a bacterial infection with Pseudomonas aeruginosa developed in the implant in her last remaining hind leg.
The infection persisted for four months despite sequential treatments with five different antibiotics after her surgeries. Throughout the antibiotic treatment efforts, the surgical wound remained open and secreting, and the metal implant was visible.
The situation was dire. To save Squeaks’ life, the veterinary team turned for help from microbiologist Ronen Hazan, a professor in the school of Dental Medicine at Hebrew University, who specializes in phage therapy and serves as the Head of the Israeli Phage Therapy Center and the Israeli Phage Bank (IPB).
Together, Professor Hazan and collaborators used a new treatment involving a meticulously designed combination of a specific phage that was targeted to kill the bacterial infection, applied topically to the surgical wound to maximize its concentration at the infection site, combined with intramuscular injections of a powerful broad-spectrum antibiotic that is used to treat a range of serious bacterial infections. Phage therapy is “personalized” because the specific strains of bacteriophages used are tailored to attack the individual patient’s infection, as determined through bacterial culture and genetic analysis.
Why use both treatments?
“Often when we combine phages and antibiotics, we get an enhanced synergistic effect,” replied the lead author of the study, veterinarian Ron Braunstein.
This treatment regimen allowed the surgical wound, which had remained open for five months, to fully heal after fourteen weeks of treatment. The successful treatment of this cat by its owners at home, where it is most comfortable, highlights the practicality and efficacy of personalized phage therapy, which could be extended to treat other pets facing similar bacterial challenges.
Additionally, it highlights the critical need for novel therapeutics like phage therapy to address the increase in antibiotic-resistant infections, which affect up to 8.5% of surgical sites following orthopedic surgeries in companion animals. These infections not only pose significant health risks to the animals but also increase the costs, suffering, and death associated with these procedures.
I think it’s interesting that this particular case was performed on an animal based on the team’s insights from treating humans first (for example, more here) — usually experimental treatments for humans are trialed in animals first. Further, Professor Hazan and his phage team in the dental school reported they successfully treated 13 of 15 so-called “lost cause” human patients chronically infected with Pseudomonas aeruginosa (more here).
This success in a companion animal can enhance treatment protocols and outcomes across a variety of bacterial infections, potentially providing fresh hope for the treatment of infections in both veterinary and human medicine.
“As the new treatment is further explored in veterinary settings, it will not only improve the health and well-being of pets, but also provide valuable data that will contribute to the broader application of phage therapy in both animals and humans,” Dr Braunstein, Professor Hazan and collaborators wrote in their paper.
Squeaks’ successful treatment under such desperate conditions will, no doubt, increase the awareness, the acceptance and the demand for phage treatment therapies by veterinarians and by pet owners. Successful phage therapies in animals will also provide additional data for their use in human medicine as well, and broaden phage therapy’s use in human medicine.
“This bridging of data could improve treatment protocols and outcomes for various bacterial infections, potentially changing the landscape of infection treatment in both veterinary and human medicine.”
The best news of all is that Squeaks is recovered and gets around very well — so well that you might not notice that she has lost a leg.
Source:
Ron Braunstein, Goran Hubanic, Ortal Yerushalmy, Sivan Oren-Alkalay, Amit Rimon, Shunit Coppenhagen-Glazer, Ofir Niv, Hilik Marom, Alin Barsheshet & Ronen Hazan (2024). Successful phage-antibiotic therapy of P. aeruginosa implant-associated infection in a Siamese cat, Veterinary Quarterly 44(1) | doi:10.1080/01652176.2024.2350661
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