Published June 6, 2023 | Version v2
Dataset Open

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

  • 1. University of Geneva, Switzerland
  • 2. Lausanne University Hospital (CHUV), Switzerland
  • 3. Felix Biotechnology, San Francisco, CA, USA
  • 4. Geneva University Hospitals, Switzerland
  • 5. Balgrist Hospital, Zurich, Switzerland
  • 6. Yale University, New Haven, CT, USA

Description

Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening MDR Pseudomonas aeruginosa infection, who was treated successfully with iterative aerosolized phage treatments specifically directed against the patient’s isolate. We followed the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples showed in patient phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates revealed a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates was multifactorial and mainly due to spontaneous chromosomal mutations.  All isolates recovered after phage treatment remained phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of P. aeruginosa lung colonization.

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Additional details

Funding

Pseudomonas aeruginosa in lung-transplant recipients: exploiting adaptation and microbial interactions to fight bacterial infections 32473B_179289
Swiss National Science Foundation