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A woman overcomes one of the worst infections known thanks to a treatment with viruses

2022-01-18T16:25:09.885Z

Scientists and doctors describe how they saved a Belgian citizen injured in an attack by a bacteria resistant to all antibiotics



Karen Northshield, on the right, together with the king and queen of Belgium, during a commemorative tribute to the terrorist attacks in Brussels held in March 2021.Belgian (POOL BENOIT DOPPAGNE/Belgian/Sipa / Cordon Press)

On March 22, 2016, Karen Northshield – 30 years old – was at the Brussels airport when a bomb exploded a few meters away. It was an Islamist terrorist attack in which 35 people died, including three of the suicide bombers. Today the amazing scientific account of how Northshield managed to save life is published. It was thanks to an experimental treatment with viruses that they made it possible to end an infection by a bacterium that had become resistant to all antibiotics, a global problem that kills more than a million people around the world every year.

Following the explosion, Northshield was rushed to the Erasmus Hospital in the Belgian capital. His heart no longer beat. The doctors managed to revive her. Part of her hip was amputated and they performed an emergency operation to save her leg. Four days later, when the situation seemed stabilized, the real hell began: a bacterium of the species

Klebsiella pneumoniae

had infected his left thigh and did not respond to treatment with any of the existing antibiotics. The doctors realized that this microbe could be more dangerous to Northshield's life than the bomb that almost killed her.

The bacterium that had infected this patient is part of ESKAPE, the group with the six most dangerous antibiotic-resistant species of microbes, according to the definition of the World Health Organization (WHO). These microorganisms pose one of the main threats to global health. The WHO estimates that these infections that are rife in hospitalized patients will kill 10 million people a year in 2050. That is three times more deaths than all those caused by covid in 2020.

"I was on duty in the ICU when this patient arrived and I took care of her for three years, two of treatment and one of rehabilitation," recalls the doctor Anaïs Eskenazi, first author of the study that describes in detail how they managed to cure to Northshield. The story is chilling: five surgeries including the removal of part of the stomach and spleen, autologous tissue transplants and finally that infection that did not go away during four months of treatment with all the existing antibiotics.

After a few months of doubts, the medical team decided to resort to an experimental treatment that is often used as a last resort: using viruses specialized in killing bacteria to fight the infection. First, we had to look for the best viruses against this bacterium, something that is not easy, since bacterial viruses, or phages, are the most numerous biological entity on Earth.

"These viruses are everywhere, in the intestines, in the throat, on the skin, there are 10 times more phages than bacteria," explains Jean-Paul Pirnay, a molecular biologist at the Queen Astrid Military Hospital in Belgium. Pirnay leads the most advanced group in Europe in the use of these to combat bacterial infections impossible to defeat with antibiotics alone. The expert turned to the Eliava Institute in Georgia, which has been applying phage therapy against infections for more than a century. It is an inheritance that goes back to the Soviet Union, where this technique flourished in World War II, especially during horrible battles such as Stalingrad, recalls Pirnay.

The team analyzed the genome of the bacterium that was infecting Northshield and began searching for a phage capable of killing it.

They found it in water from a sewer.

After preparing the viruses for therapy, they were administered to the patient directly into the infected area.

The combined phage and antibiotic therapy eliminated the infection completely, the medical team reported Tuesday in

Nature Communications

.

Three years after the Northshield treatment, she can walk again with the help of crutches and even participates in sporting events, as she herself has recounted in the book

Dans le souffle de la bombe

(in the blast wave), published in French on last year.

“This is one of the most promising treatments against resistant bacteria”, highlights Eskenazi. These microbes often accumulate in thin layers attached to surgery or treatment materials, such as Northshield coronary prostheses or metal braces affixed to broken bones. "A team from the University of Leiden, in the Netherlands, created these same films in the laboratory and showed that the combined therapy of phages and antibiotics was able to eliminate the infection much better than these treatments separately", details Eskenazi.

Part of the success is due to "phage training," explains Pirnay. This consists of directing the evolution of these viruses by cultivating one generation after another together with the bacteria that infect the patient. In each round, the viruses that kill the most bacteria are selected and the next one is passed. The result is an elite troop against that particular pathogen. “The phages are harmless to people because we have been evolving alongside them for millions of years. The only drawback of this type of therapy is its specificity; For each bacterium, you have to find the phage that can fight it”, explains Pirnay.

In recent years, Pirnay's team has treated more than 100 patients in 12 countries with phages, including one at the Virgen de la Macarena Hospital in Seville. He was a 58-year-old man who had had a blood infection caused by

Pseudomonas aeruginosa

for a year , another of the most dangerous group of bacteria.

The doctors asked Pirnay for a phage preparation and applied it to the patient, who overcame the infection, explains María del Mar Tomás, an expert in phages at the A Coruña University Hospital, who participated in the treatment of this patient. “The phages make the bacteria stop being resistant to antibiotics”, details the microbiologist. “Bacterial viruses attack the same molecular targets that bacteria use to avoid the effect of antibiotics. If you first administer phages and then antibiotics, you block their resistance and the infections subside”, he points out.

Pilar Domingo Calap is a phage hunter. "We find them anywhere, wastewater, ditches, soil, even in the plants in the city center," explains this microbiologist from the Institute of Integrative Systems Biology of Valencia. His laboratory has found more than 200 types of phages capable of combating

K. pneumoniae

. He also works on specific cases of a few patients with resistant infections, for example a boy with cystic fibrosis who is waiting for a double lung transplant and who suffers from an infection resistant to antibiotics, he explains.

These therapies are still taking their first steps and their widespread application is complicated, explains Domingo. “In Europe in general, except in Eastern countries, the use of phages in clinical practice is not regulated. Specific legislation is necessary to be able to use them routinely. In France or Belgium, the governments are already investing in these experimental therapies, although there is still a long way to go to regularize them. In Spain it is only allowed as compassionate treatment. From the Spanish Network of Bacteriophages we are trying to get the Medicines Agency to allow us to regularize its use”, he details.

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Source: elparis

All news articles on 2022-01-18

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