A woman's exuding wound did not heal after nearly two years of antibiotic treatments to overcome the bacterial infection. So her doctors triggered viruses to kill the superbug.
The experimental therapy involved specifically viruses that is contagious bacteria, known as bacteriophages or "phages" for short. And although antibiotics alone had failed to cure the patient's infection, a combination of antibiotics and specialist therapy seemed to do the trick, according to a new report on the case, published Tuesday (January 18) in the journal Nature communication.
"A few days after the treatment, the patient's wounds were already dry," which means that pus no longer leaked from the wound, "and the skin changed color from greyish to pink," Dr. Anaïs Eskenazi, the study's first author and specialist. in Internal Medicine and Infectious Diseases at CUB-Erasme Hospital in Brussels, Belgium, WordsSideKick.com told in an email.
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Three months after the subject therapy, the doctors could not find any lingering signs of superbug in the patient, and her wounds healed steadily. And in the three years after treatment, the bacterial infection has not returned.
"I see this as compelling evidence that you can get antibiotic and subject synergy," meaning bacteriophages and drugs work together to kill superbugs more effectively, said Paul Turner, a professor of ecology and evolutionary biology at Yale University, who was not involved. in the study. This kind of synergistic effect has emerged in previous studies, including Turner's own work, and the new case report provides further evidence of how this effect may be useful to human patients.
The concept of using viruses to kill bacteria first emerged more than a century ago, almost a decade before the discovery of penicillin in 1928, according to a 2017 report in World Journal of Gastrointestinal Pharmacology and Therapeutics. However, researchers' understanding of phages was limited at the time, and after the discovery and pharmaceutical production of antibiotics, the field was largely abandoned. However, various research groups in the former Soviet Union and Eastern Europe continued to study occupational therapy and ran human trials with the treatment with varying degrees of success.
Interest in subject therapy resurfaced within the last decade as scientists began searching for new strategies to eliminate antibiotic-resistant superbugs. One caveat is that subject therapy is not foolproof - just as bacteria can develop into outsmarting antibiotics, they can also develop resistance to specific phages, according to a 2021 report in the journal Proceedings of the National Academy of Sciences. The difference is that phages can easily evolve to overcome that resistance and fight back. Plus, bacteria cannot easily trade phage resistance genes as they do antibiotic resistance genes, Turner noted.
With this in mind, researchers are now studying how they can take advantage of the subjects' genetic flexibility in the fight against superbugs. The new case study provides an example of how phages can be "trained" to kill specific bacteria very effectively through a process called "pre-adaptation".
The patient involved in this case developed a superbug infection after a major operation on her left thigh. Her femur, or femur, was broken during the bombing that took place at Brussels airport in March 2016, and doctors used pins, screws and a stabilization frame to fix it. bone in place after taking care of her other traumatic injuries.
Unfortunately, the woman's surgical wound was subsequently infected with Klebsiella pneumoniae, a bacterium that causes various health-related infections, according to the Centers for Disease Control and Prevention (CDC). This means that patients may be exposed to the error while using a ventilator, receiving medication through an IV, or undergoing surgery, as in this patient's case.
Many Klebsiella bacteria have developed resistance to antibiotics, according to the CDC. In this case, biopsies revealed that the patient carried two strains of K. pneumoniae, one of which exhibited an "extensive drug-resistant phenotype." After three months in the hospital, "the patient had been under different regimens with antibiotics, but the femoral fracture was still not consolidated and the infection continued," Eskenazi said. At this point, the medical team began to consider occupational therapy.
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The patient was a good candidate for specialist therapy, in part because her infection was associated with biofilm, said Eskenazi. Biofilms are formed when colonies of bacteria adhere to a surface and produce a 3D matrix that surrounds their cells, as a kind of protective barrier. Antibiotics have a hard time penetrating these films, and even when they do, some bacterial cells survive the antibiotic attack by going to sleep. Antibiotics typically work by interfering with the function of a bacterial cell, which essentially causes it to short-circuit so that the substances do not act on resting cells. Live Science previously reported.
But even when antibiotics do not destroy bacteria locked behind biofilm, specialist therapy can reduce these superbugs, Eskenazi said.
"Many phages are known to have the capacity to destroy the biofilm and thus make it easier for antibiotics to achieve their goals," she said. To identify the best subject for the job, the medical team took samples of the patient's K. pneumoniae strains and sent them to the George Eliava Institute of Bacteriophages, Microbiology and Virology, in Tbilisi, Georgia, a nonprofit institute studying subjects and their potential uses.
Based on the department's extensive library of bacteriophages, researchers identified a subject that could effectively infect and kill the patient's K. pneumoniae originates. They then placed the phage and the bacterial strains in laboratory dishes, which enabled the phage to infect the bacteria, make copies of itself, and detect genetic mutations while doing so; over time, these cuculative mutations helped the phages to kill the bacteria more effectively. At the end of this experiment, the researchers sifted through the resulting phage mutants to identify the very best bactericides, and then repeated the process with the "winning" phages.
After 15 rounds of this process, the team produced a phage mutant that was potent enough to combat the patient's K. pneumoniae. This type of targeted evolution, which the authors called "pre-adaptation," has been used in other subject therapy studies to make a bacteriophage more potent before setting it against a bacterial enemy, Turner said.
The patient was initially approved to receive this optimized occupational therapy in November 2016, after the ethics committee at Erasme Hospital gave the green light to the procedure. However, due to lack of consensus among the treating physicians, the treatment was put on hold until February 2018. By that time, 702 days had passed since the patient's first injuries and she had been on antibiotics for a large part of the time.
The patient finally received the professional therapy after a surgical procedure in which the doctors removed dead and damaged tissue from her wounds; introduced bone grafts that had been "impregnated" with an antibiotic; and replaced the frame that helped stabilize her broken bone. At the end of this procedure, the team inserted a catheter into the wound through which they could send the pre-adapted phages.
They left this catheter in place for six days and used specialist therapy every day while also giving the patient antibiotics. The patient began to show improvement within two days after starting subject therapy, but on top of that she was also switched to a newly available antibiotic against drug resistant K. pneumoniae, said Eskenazi.
Three months later, the patient was free of infection and both her wounds and femur were finally recovering. At this point, the doctors removed the stabilizing frame on the patient's leg and discontinued all of her antibiotic treatments.
"Three years after combination therapy with phage antibiotics, the patient has regained ambulation and mobility, usually using crutches, and attending sporting events," such as cycling, the study authors reported. "And there is no sign of repetition K. pneumoniae infection."
The case study suggests that a combination of subject therapy and antibiotics can effectively treat drug resistant K. pneumoniae, Turner said. The case study cannot show how much of the patient's improvement could be attributed to the subjects and how much came down to her new course of antibiotics. However, given that the patient showed some improvement prior to switching to antibiotics and that no previous antibiotics had worked at all, the results suggest that the subjects made a difference.
In the future, Turner said he expects that as the use of subject therapy becomes more widespread, treatment will sometimes be used in conjunction with antibiotics, as in this case, although it could also be effectively isolated, "especially if you are going after pan-drug-resistant bacteria ", which do not respond to any antibiotics, he said.
To find out how occupational therapy can best be used, we will need to collect more data through large clinical trials, not just isolated case reports, he said. "In fact, the future of subject therapy rests on abundant data from clinical trials," he said. "This is just the gold standard ... subjects must be kept up to the same gold standard." Such experiments are already underway.
Originally published on Live Science.