In January 2020, a 56-year-old man arrived at a Boston hospital complaining of a skin rash that had spread down his left arm. In a few months, his situation became so critical that he had to be admitted to hospital. The story of how he overcame this condition is a new example of how viruses can be used to fight antibiotic-resistant superbugs, a global pandemic that kills more than AIDS, malaria and some cancers every year.
Antibiotic-resistant bacteria prey on people whose immune system is already weakened by other diseases or treatments. These patients – hundreds of millions worldwide – are the most at risk of serious complications or even death from these infections.
The man who went to Brigham and Women’s Hospital that January 2020 was the perfect victim. He had chronic kidney disease and suffered from arthritis in his joints due to a problem in his immune system that also caused neurological complications. The doctors began to treat him with antibiotics but his situation didn’t improve. A month later he had to be admitted. The skin lesions on his arm became so large that doctors had to cut them open to remove the dead tissue. None of the antimicrobials used could overcome the bacteria causing the infection. The bacteria was Mycobacterium chelonae, a pathogen from the tuberculosis family that can cause rashes and widespread damage to other organs. The US patient also suffered serious side effects from the toxicity of all the antibiotics he received.
A year later the infection had spread and the abscesses were getting bigger and more painful. At that time, the Venezuelan-born doctor Francisco M. Marty suggested to his colleagues that perhaps a virus was capable of curing the patient.
The doctor was referring to bacteriophages, viruses specialized in killing bacteria. For every known bacterium there is probably a virus capable of entering it and killing it. All the doctors had to do was find the right pathogen. The doctors extracted microbes from the patient’s wounds, sequenced their genome and searched among 20 phages that had been studied before to eliminate infections with another superbug of the same family. This is how Muddy was identified, a phage that easily dealt with M. chelonae in the laboratory.
Doctors got permission to use Muddy as an experimental treatment and injected it into the patient intravenously. They also continued with antibiotic treatment. The lesions improved in just two weeks. The patient had no serious side effects. Currently, he continues to receive viral treatment and shows no signs of infection, explains Jessica Little, a Brigham physician and lead author of the study that describes the case, published Tuesday in Nature Communications.
“This is the first time that phage therapy has been applied to M. chelonae,” explains Little. “In addition, it is the first case in which results are achieved with a single virus; normally cocktails of several phages are used,” she adds. The 56-year-old joins the small but growing number of patients who have overcome superbug infections thanks to this experimental therapy.
“It is the first case in which results are achieved with a single virus; normally cocktails of several phages are used”
Jessica Little, Brigham physician and lead author of the study
The medical team has not identified the patient to preserve his privacy, but has published images showing the rapid evolution of his injuries after the experimental treatment. His case also raises an important question. The patient developed antibodies against the Muddy virus, but despite this, there were no complications or relapses, Little points out. “We need to better understand the interaction between these viruses and the patient’s immune system, and whether this can affect the success of treatment.”
The study includes an acknowledgment to Francisco M. Marty, the Brigham physician who first suggested phages and who died on April 9, 2021, after falling off a cliff while taking photos in the Dominican Republic while on vacation.
Researcher Pilar Domingo-Calap is one of the leading experts in Spain on the use of phages to defeat recalcitrant infections. She recently managed to isolate phages to treat Dani Río, an 18-year-old who had been on the verge of death from an infection similar to that of the American patient. “Using phages for compassionate treatment is not new, but the fact that there are more and more cases with positive results reinforces the need to regulate their use in clinical settings,” she says.
At the moment bacteriophages are only used as a last resort, when there are no other therapeutic options. “Based on the patients’ own strains, we look for phages in the environment and characterize them,” says Domingo-Calap. Phages are sometimes found in the least expected places, such as hospital wastewater systems, which have the optimal conditions for antibiotic-resistant bacteria. One of the current research goals is to create a “library” of all identified phages, organized according to the superbug they can kill. Another goal is to create phage cocktails against the most common superbugs that can be used widely across the population.
Superbugs are a direct consequence of antibiotic abuse. The indiscriminate use to preventively treat any type of infection or to fatten cattle has caused many bacteria to develop immunity against many or all known antibiotics. The goal now is to prevent the same thing from happening with phages. That is why “lytic” viruses – which penetrate the bacteria and literally destroy it – are sought. It is important to ensure that viruses do not integrate their genome with parts of the bacteria’s DNA. If this happens, they could become a vehicle for transmission, which would return us to square one in the fight against this worrying pandemic.