A study with Vall d'Hebron participation demonstrates the safety of therapy with viruses to combat multidrug-resistant bacteria

A study published in Clinical Infectious Diseases has shown that therapy with bacteriophage viruses or phages to treat infections caused by multidrug-resistant bacteria is safe, and is effective in more than 50% of the cases. The study has assessed 20 cases of compassionate use of this treatment, which is used only in very complex patients in whom antibiotic therapy has not yielded the expected results. Vall d'Hebron University Hospital has participated in the study with two patients.

Microbacteria resistant to antibiotics are becoming more and more common. Infections with non-tuberculous mycobacteria, such as Mycobacterium abscessus, are particularly difficult to treat and require very high and prolonged doses of antibiotics, with the subsequent increase in undesirable side effects. One sector of the population particularly vulnerable to these infections are patients with Cystic Fibrosis or other pathologies that cause chronic dilatation of the bronchus, as they start from a complicated clinical baseline. One of the authors of the study, Dr. Cristina Berastegui, from the Pneumology Service at Vall d'Hebron and the Pneumology research group at Vall d'Hebron Research Institute (VHIR), comments: "This increase in antibiotic resistance requires us to look for new therapies for those patients for whom traditional treatment is no longer enough".

Bacteriophages are viruses that infect bacteria, which means that they use bacteria as a host cell to replicate and in this process the bacteria are destroyed. The difficulty of the therapy lies in finding the right phage for each case, i.e. a bacteriophage capable of infecting the bacteria present in the patient. Once the appropriate phage was selected, the medical team injected it intravenously into patients, in some cases supplemented by an aerosol administration of the same virus.

The use of this therapy did not replace, but rather complemented, antibiotics. The ultimate goal is to have enough reduction of the bacterial colony to allow the traditional drugs to do their job and eradicate the infection, or at least reduce its extent and improve the patient's clinical status.

Of the twenty patients analysed, eleven had significant improvements, four had no response and five had inconclusive results. The limited sample size and the complexity of all the cases presented complicates drawing clear conclusions as to what factors determine the success or failure of the treatment. None of the patients had rejection, but eight created antibodies against the viruses. Even so, these immune system responses could not be linked to the success or failure of the therapy.

A treatment designed for very specific cases

Dr. Susana Gómez, from the Pneumology research group at VHIR, explains that the aim "is not to create a new treatment that can be widely used, but to provide a response to highly complex cases when conventional treatments have failed". The main limitation for a more massive use of this technique is that it requires a high degree of personalisation. "We have a small library of viruses and each one only attacks a few specific bacteria. Matching the bacteria present in the patient with their bacteriophage is a laborious and sometimes impossible process".

That is why they focus the treatment on compassionate use for patients with previous respiratory diseases and in whom antibiotic treatment is not effective. "These are very complicated cases for which no solution could be found until now," explains Dr Berastegui, "This therapy gives them a new opportunity".

The research team hopes that with new studies and further research, the library of available bacteriophages will be expanded and the number of potential beneficiaries will increase.