Eradication of extensively drug resistant Pseudomonas aeruginosa causing ventilator-associated pneumonia in acute lymphoblastic leukemia patient using phage therapy

Ventilator-associated pneumonia (VAP) are among the most frequent hospital-acquired infections, representing a significant morbidity and mortality risk. Increasing antibiotic resistance acquired by major bacterial pathogens associated with VAP, especially Pseudomonas aeruginosa, is rapidly narrowing therapeutic options with standard-of-care antibiotics. In response to the urgent need for alternative therapeutic approaches, phage therapy has recently reemerged as an efficacious way to combat resistant infections. Here, we report the case of a 17-year-old patient diagnosed with acute lymphoblastic leukemia who suffered from persistent VAP and sepsis caused by extensively drug-resistant P. aeruginosa for over 6 months, which originated after decompressive craniectomy due to hemorrhagic stroke. The patient received a 12-day nebulized treatment with a single phage belonging to a new Pakpunavirus species, in combination with intravenous antibiotics. This therapy was well tolerated and was associated with clinical improvement and microbiological eradication of P. aeruginosa, eventually allowing the discharge of the patient from the intensive care unit and from hospital. In vitro testing of the selected phage showed a broad-host range and anti-biofilm activity in a panel of unrelated clinical P. aeruginosa strains. Together, our results support the use of individually-tailored phage preparations and its potential scalability and transition to semi-personalized medicines using broader host-range phages, as a promising alternative to combat the antimicrobial resistance pandemic.