A woman with a wound infected with drug-resistant bacteria for nearly two years has been successfully treated with a bacteria-infecting virus, her doctors have reported in the journal Nature Communications.
On March 22, 2016, the 30-year-old sustained an injury to her leg during a suicide bombing at Brussels Airport. While being treated at the intensive care unit at the Erasme Hospital, she had a heart attack due to the blood loss from the extensive wounds. Following "aggressive" surgery – including the removal of a part of her pelvis – her condition was stabilized.
Unfortunately, four days after admission she entered septic shock from a bacterial infection in her wound. She had been treated with a wide range of antibiotics when she came to the hospital, but with no apparent effect.
"To control the infection, a grand dorsal muscle autograft was used to close the major blast wound on the left leg, 14 days after admission," the team wrote. "However, the graft immediately necrotized superficially, requiring further debridement."
With the antibiotics causing further complications, and more dead tissue requiring the removal of her stomach and spleen, the course of high-dose antibiotics was discontinued.
At this point, they decided to attempt phage therapy, where a virus is used to fight off bacterial infections.
The idea of using bacteriophages (viruses that infect bacteria) dates back a surprisingly long way, first used in 1919 by French microbiologist Félix d'Hérelle to treat children with severe dysentery. However, the therapy could now become more common due to the rise of antibiotic-resistant infections.
"Bacteriophages, also known as phages, survive by infecting bacteria, replicating and bursting out from their host, which destroys the bacterium," Kevin Doxzen, Hoffmann Postdoctoral Fellow at Arizona State University explained in a piece in 2021.
One of the great things about phages is how adaptable they are. In this case, the team identified a phage that could be effective at killing the bacteria named Klebsiella pneumoniae infecting the patient, and set about making it an even more effective fighter.
"Phage vB_KpnM_M1 (M1) was shown to exhibit the highest activity against the patient’s K. pneumoniae isolates," they wrote. "It was isolated from a sewage water sample in Tbilisi, in 2012."
They put the phage in a lab dish with the bacteria strain from the patient, and let it do its thing. After each round of letting the virus kill the bacteria – where some of the phages picked up mutations making them more effective bacteria killers – they selected the most effective phages and set them on their task once more in the lab. Eventually, they ended up with phages that could fight the bacteria's defenses more effectively.
"Fifteen rounds of co-evolution [...] significantly reduced the incidence of bacterial phage resistance."
With other treatment options exhausted, the ethical board granted permission, and the patient her consent, to go ahead with the experimental phage treatment in February 2018. Three months after the therapy, the patient was doing much better.
"The skin graft appeared vascularized and viable, the sinus tract was closed and dry, and pus no longer discharged from the pin sites of the external fixator, indicating that the [infection] was controlled," they write in the report.
"The patient’s general condition had also improved, with a weight gain of 5 kg and a restored muscle function of the left thigh."
As well as the therapy, antibiotics were administered, likely helping with the infection. A week later, bone fragments that had come loose while removing a frame that held her bones in place were tested, and no growth of K. pneumoniae was found.
"Pre-adapted phage-antibiotic combination therapy ultimately led to a positive clinical outcome," the team concluded.