With viruses against bacteria – bacteriophage therapy as a hope against multi-resistant germs

Hope in the fight against multi-resistant germs: phages that attack bacteria. (Illustration) (imago images / Westend61)

Brussels, spring 2016: In the Erasmus Hospital, a young woman is struggling to survive after a bomb attack. Among other things, she survives a septic shock and a massive fungal infection. Only the broken femur, which is held together with a metal frame from the outside, just won’t heal.

Multi-resistant bacteria of the species Klebsiella pneumoniae are to blame. At that time, the doctor Anaïs Eskénazi was also responsible. Today she works in a hospital in French Guiana:

“The problem was that there were no effective antibiotics. So I started researching and I came across phage therapy in a book about extraordinary diagnostic and treatment methods.”

Phages can kill bacteria

Phages are viruses that are found almost everywhere in the environment and can kill bacteria. In Georgia, Poland or Russia, for example, bacterial infections have been treated with phages for almost 100 years. But: “In the scientific community in the West, the idea of ​​treating bacteria with viruses was met with skepticism for a long time. We first had to bring well-founded know-how to the clinic before we could even propose it to the other doctors in the team.”

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Anaïs Eskénazi contacted Belgian phage expert Jean-Paul Pirnay at Queen Astrid Military Hospital. He has been collaborating with the Georgian Eliava Institute for many years. A suitable virus against the stubborn bacterial strain in the thigh wound was quickly found in the archives of the institute. It originally came from a local sewage sample.

Optimized viruses from the laboratory

What happened then? In order to increase their effectiveness, the selected phages were repeatedly brought together with the bacteria from the wound in the laboratory, explains Jean-Paul Pirnay:

“You dilute the mixture just enough to see phage activity and then continue working with those viruses. It’s like natural selection, only faster.”

After 15 rounds of selection, the team was satisfied. Genetic analyzes also showed that the optimized phage had no genes on board that could lead to further antibiotic resistance and no blueprints for toxins. The researchers also tested how well a combination of phages and antibiotics worked.

wound completely healed

“The overall activity was not just additive. There was indeed a synergy effect. We were able to show this in liquids and on a bacterial biofilm. We took the bacterium strain from the patient samples and first spiked it with just antibiotics, then just phages and then a combination of both. And we saw that the combination is very effective.”

A combination was finally used in the Brussels hospital, albeit only after almost two years, when pure antibiotic therapy was officially considered a failure. According to the study published in the journal “Nature Communications”, there was an improvement just a few days after the phage administration. After three months, the wound had healed completely and the femur had grown back together. There were apparently no undesirable side effects.

Controlled studies are lacking

However, it is only a case study. Whether this type of phage therapy is also suitable for other patients, whether antibiotics and phages should be administered simultaneously or one after the other, cannot be deduced. This requires large-scale, controlled studies and the support of companies for many current therapy inquiries, says Jean-Paul Pirnay.

Pirnay reports that his hospital receives many such inquiries: “On average, one every day. But we are not a pharmaceutical company, we are researchers at a clinic. We cannot treat up to 400 patients a year and have to do a triage. I think it is It is time for companies to step in and invest.”


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