A HUG patient saved by natural viruses called bacteriophages

For the first time, a multidisciplinary team from the University Hospitals of Geneva (HUG) and the University of Geneva (UNIGE) has successfully treated a patient suffering from an antibiotic-resistant chronic bacterial lung infection using bacteriophages.

This Swiss first was achieved thanks to a highly personalised, multidisciplinary approach involving the selection of a bacteriophage (a virus that attacks bacteria) specific to the patient’s multi-resistant bacteria. Phages are one of the strategies being considered to combat the scourge of bacterial antibiotic resistance. However, much remains to be done in order to select those that are specific to each individual, establish treatment protocols, understand the side effects and avoid the emergence of phage-resistant strains. These results have been published in the journal Nature Communications.

An unconventional treatment

In this publication, a team from the HUG and the UNIGE used phage therapy to successfully treat a 41-year-old patient suffering from chronic lung disease caused by a multiresistant strain of the bacterium Pseudomonas aeruginosa. After six months in hospital at the HUG, totally dependent on continuous intravenous antibiotic therapy and with no prospect of improvement, the patient received an experimental phage therapy as a last resort, authorised on a compassionate basis. Thanks to this treatment, he was finally able to leave hospital, regain his independence and return to work.
Phage therapy is an approach that uses bacteriophages, also known as phages, to fight bacterial infections. In the case of bacteria, these are “natural viruses” capable of targeting specific bacterial strains without infecting human cells. Used in combination with antibiotics, they circumvent antibiotic resistance. Although this strategy is promising, basic scientific and clinical data are still needed to develop treatments that are effective, safe and approved by the health authorities, which is not yet the case.

A highly individualised therapeutic approach

“Bacteria can develop resistance to both phages and antibiotics. In order to increase our chances of therapeutic success, it was therefore crucial to select the appropriate phage for the bacterial strain specifically infecting the patient prior to phage therapy”, stresses Dr Thilo Köhler, co-leader of the research group in the Department of Microbiology and Molecular Medicine at the Faculty of Medicine, University of Geneva.

To do this, the HUG and UNIGE team first isolated the bacteria from the patient’s respiratory secretions, then determined the type of bacteria present, their genetic profile and their resistance to both antibiotics and a phage bank. After an intensive but unsuccessful search of the phage banks at the HUG, the CHUV and the European Phage Centre at the Hôpital militaire Reine Astride in Brussels, involving hundreds of different phages, a phage active on the patient’s bacteria was finally identified at Yale University in the United States.

Efficacy with no adverse effects

The phages were administered by aerosol while maintaining intravenous antibiotics. The patient’s improvement was spectacular, without any side effects, confirming the efficacy and safety of the phages. Detailed monitoring of the bacteria and phages in the patient’s secretions proves that the phage replicates only its bacterial target, without the emergence of more resistant or dangerous bacteria. “However, it is important to emphasise that phage therapy is used as a complement to antibiotic therapy, not as a replacement,” stresses Prof Christian van Delden, Associate Physician at the HUG Infectious Diseases Department and Professor in the Department of Medicine at the UNIGE Faculty of Medicine, before emphasising the importance of research into new strategies for combating antibiotic resistance. He highlights the success of the translational approach used: starting with the patient, passing through the laboratory, and returning to the patient. The Geneva team also praises the collaboration with the American group, which generously provided the phages free of charge. Christian van Delden confirms: “Without them, this life could not have been saved”.

Combating antibiotic resistance

Antibiotic resistance is a global health emergency, causing millions of deaths worldwide every year – 1.7 million in 2019, according to the World Health Organisation. This scourge is mainly due to the intrinsic properties of bacteria. In nature, as in the human body, bacteria form an ecosystem with their enemies, i.e. other bacterial species, fungi and bacteriophages. To cope with this, bacteria have a natural ability to evolve rapidly through mutations, enabling them not only to adapt to their environment, but also to evade antibiotics. Prolonged or repeated exposure to antibiotics therefore automatically leads to the selection of resistant bacterial strains. Phage therapy is one of the promising strategies for overcoming this major health problem.

Source: Press Release