New findings on phage-antibiotic combination therapy

Phages and antibiotics work better together against pneumonia

Using lab experiments, researchers from Charité – Universitätsmedizin Berlin have gained new insights into the combination of phages and antibiotics to treat pneumonia. Here, Chantal Weissfuss, first author of the study, and study lead PD Dr. Geraldine Nouailles answer questions about their research findings.

What was the research question or scientific inquiry behind your study?

After mechanical ventilation in the intensive care unit, patients can develop lung infections called ventilator-associated pneumonia (VAP). These infections are often caused by bacteria like Pseudomonas aeruginosa, which are resistant to various antibiotics (called multi-resistant bacteria). We wanted to see if combining an antibiotic with phages (viruses that attack and kill bacteria) could improve the treatment of VAP caused by Pseudomonas. Phages can kill bacteria even if they are resistant to antibiotics.

How did you approach the topic?

We developed a mouse model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa. We treated the mice in three different ways: either with a mixture of phages that target Pseudomonas, with the antibiotic meropenem, or with a combination of the two. We also tested the treatments on human lung cells in the lab to see how they affected the lung barrier and cells stretched by ventilation. Additionally, we checked for possible side effects from killing the bacteria.

What did you discover?

The results were very promising: in mice, the combination of phages and antibiotics worked best. The bacteria were killed quickly and completely, the mice recovered faster, showed fewer signs of infection, and had less lung damage. There were no side effects. We confirmed these positive results in the human lung cell experiments as well.

Was there anything that surprised you?

One surprising finding was that we could lower the doses of both the antibiotic and the phage mixture without losing effectiveness. This is important because lower doses can help minimize potential side effects.

What’s your takeaway?

Overall, combining phages and antibiotics appears to be a very promising approach to treating pneumonia caused by multi-resistant bacteria. Phages offer fast and specific bacterial killing, while antibiotics provide lasting protection. We did not observe new phage-resistant bacteria or damage to the lungs or other organs by the antibiotic. However, further studies are necessary before this therapy can be routinely used for patients.


Contact

Chantal Weissfuss & PD Dr.-Ing. Geraldine Nouailles
Speciality Network: Infectious Diseases and Respiratory Medicine
Charité – Universitätsmedizin Berlin


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