Noemi G. Gomez |
Madrid (EFE).- Bacteria resistant to antibiotics are increasing worldwide and it is increasingly difficult to find new drugs, making diseases such as tuberculosis or pneumonia difficult (sometimes impossible) to treat. Science is looking for alternatives and one of the most promising is phage therapy.
Still in the experimental phase, but with successful cases in various hospitals around the world, such as that of a woman with a “Klebsiella pneumoniae” infection, a victim of the 2016 attack at the Brussels airport, this treatment uses viruses called bacteriophages or phages. , which exclusively infect bacteria.
It has been shown that they are capable of combating the most complex bacterial infections, especially when combined with antibiotics, summarized to EFE by researchers Iñaki Comas (from the Institute of Biomedicine of Valencia) and Pilar Domingo-Calap (Institute of Integrative Systems Biology ( I2SysBio, CSIC-Universitat de València).
The problem of overuse of antibiotics
Antibiotics represent one of the most revolutionary discoveries. They laid the foundations of modern medicine, allowing not only to cure previously lethal infections, but also to perform transformative interventions such as transplants, mentions the Higher Council for Scientific Research (CSIC) in a monograph from its “Science for Public Policies” collection.
Unfortunately, he adds, its excessive use has caused a spectacular increase in resistance in bacteria – which mutate.
This is today one of the greatest threats to global health, food security and development, and its increase is reaching dangerous levels, indicates the World Health Organization.
According to a study by The Lancet, which analyzed 204 countries, 1.2 million people die every year from antibiotic-resistant infections and this number could multiply tenfold by 2050. Urgent action is needed.
“It is increasingly difficult to find an antibiotic that is truly new, so we have to look for alternatives, and one of the most interesting is phage therapy,” declares Iñaki Comas, from the Institute of Biomedicine of Valencia (IBV) and coordinator of the CSIC Global Health Platform.
Phages, more than a century of history
Bacteriophages were discovered just over a century ago by the French-Canadian microbiologist Félix d’Herelle, who in 1919 used the therapy for the first time with patients.
However, the discovery of penicillin in 1928 and its subsequent commercialization and boom in antibiotics overthrew phage therapy research, except in some countries of the former Soviet Union, such as Georgia, which, although with ups and downs in its history, is today a benchmark for through his George Eliava Institute, in Tiflis (Eliava worked with d’Herelle and was executed in 1937).
But over the years, and largely due to misuse (years of antibiotics without a prescription and abuse in agronomy) resistance began to emerge, causing longer hospital stays and increasing mortality and costs; For example, a normal case of tuberculosis costs about 200 euros to treat in Europe, but 30,000 euros if the “Mycobacterium tuberculosis” bacterium is multiresistant.
And in extreme cases, when it is extremely resistant, costs can increase up to 200,000 euros, recalls Comas.
Precisely this multi- and super-resistance, for which antimicrobials on the market do not work, are what are worrying and have made the scientific focus return to phages.
Phage dynamics
Bacteriophages are viruses that infect and kill bacteria, they are very abundant viruses in nature and very specific, explains Pilar Domingo-Calap, from the Institute of Integrative Systems Biology (I2SysBio, CSIC-Universitat de València).
They recognize a specific bacterium and use it; they use the cellular machinery of this to create new viruses and enter into a kind of “arms race” against the bacteria until they are able to eradicate it.
They therefore eliminate only the pathogenic bacteria that cause the disease, an ability that makes this therapy a good candidate for personalized, precision medicine.

But this specificity can also be a disadvantage because we must find an appropriate mixture of phages for each type of infection and since it is a virus, unlike a drug with a chemical structure, its pharmacodynamics are almost impossible to predict and measure.
In each patient the result is different, which is why we have to change the way we do clinical trials and how we understand the results. “We are moving towards a very personalized medicine”, adds Domingo-Calap, who participated, together with Comas, in the Cicero conference of the CSIC to talk about his research against superbugs.
They begin to be produced in Spain
Furthermore, there is a lack of adequate regulation, although work is already being done on this at the European level. Now phages can only be used as compassionate therapy and there are numerous success stories, some also in Spanish hospitals (with phages imported from the United States and Belgium).
These are already beginning to be produced in Spain; Domingo-Calap’s laboratory has managed to isolate them, characterize them and develop them as therapeutic tools.
In fact, in April this researcher created Evolving Therapeutics SL, a “spin-off” located in the scientific park of the University of Valencia to produce biotechnological solutions based on these viruses, which have already been tested – in an initial phase – in some few patients.
One of the best-known cases of treatment with these viruses, published in Nature Communications, is that of a 30-year-old woman, victim of the 2016 attack at the Brussels airport, with a bacterial infection related to a fracture, for which the treatment antibiotics had failed for almost two years.
After the interventions in the operating room and his stabilization, the victim evolved into septic shock due to an infection in the surgical wound on the left thigh, despite antibiotic treatment. The team at the Erasme Hospital in Brussels then selected and adapted a specific bacteriophage for the “K. pneumoniae”, therapy that combined with antibiotics.
This resulted in a clinical and microbiological improvement of the wounds, and their general condition.