Sequential phage therapy against Pseudomonas aeruginosa colonising a chronic venous skin ulcer
Chronic venous ulcers are often complicated by persistent bacterial colonisation and biofilm formation, impairing healing and limiting definitive surgical closure. We report the compassionate-use treatment of a chronic venous leg ulcer, presumed to be adversely affected by persistent Pseudomonas aeruginosa colonisation using sequential topical administration of two lytic bacteriophages, TIVP-27M and LPS-26. Phage therapy was well tolerated and associated with improvement in clinically suspected biofilm-related indicators. Surgical ulcer coverage was subsequently performed. Longitudinal microbiological and genomic analyses showed persistence of a clonal P. aeruginosa lineage, with transient emergence of a phage-resistant isolate on day 16. This isolate exhibited impaired growth and reduced swimming, swarming, and twitching motility, alongside genomic alterations affecting surface-associated and motility-related functions, including pilR , flgE , galU , and hmgA . Later isolates remained susceptible to both phages. These findings support personalised topical phage therapy as a potential adjunctive strategy for selected chronic wounds while highlighting complex evolutionary dynamics during treatment.
Authors
- Francesco Petri (ORCID: https://orcid.org/0000-0003-0125-9551)
- Gherard Batisti Biffignandi (ORCID: https://orcid.org/0000-0003-3108-6313)
- Simona Landonio
- Irene Mileto (ORCID: https://orcid.org/0009-0007-5272-3138)
- Caterina Ferretti
- Sara Giordana Rimoldi (ORCID: https://orcid.org/0000-0003-1935-8750)
- Greta Petazzoni (ORCID: https://orcid.org/0000-0003-3537-8006)
- Novella Cesta (ORCID: https://orcid.org/0000-0002-8767-7094)
- Mariagrazia Di Luca (ORCID: https://orcid.org/0000-0002-0688-034X)
- Maria Vittoria Cossu (ORCID: https://orcid.org/0000-0002-6984-3028)
- Michela Pellegrini (ORCID: https://orcid.org/0000-0003-4554-7344)
- Matteo Passerini (ORCID: https://orcid.org/0000-0002-8120-1853)
- Andrea Gori (ORCID: https://orcid.org/0000-0001-6587-4794)
- Sara Bolognini (ORCID: https://orcid.org/0009-0007-4574-4512)
- GINEVRA MORELLI
- Ahmed El Goutbi
- Rita Carminati
- Benjamin K. Chan
Institutions
- University of Pisa (IT)
- University of Milan (IT)
- Yale University (US)
- European Society of Clinical Microbiology and Infectious Diseases (CH)
- Policlinico San Matteo Fondazione (IT)
- ASST Fatebenefratelli Sacco (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
- International Centre for Genetic Engineering and Biotechnology (IT)
Publication Details
- Journal
- npj Antimicrobials and Resistance
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1038/s44259-026-00283-8
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministero della Salute
- NextGenerationEU