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.