Melissa Pitton, Luca G Valente, Simone Oberhaensli, Bülent Gözel, Stephan M Jakob, Parham Sendi, Monika Fürholz, David R Cameron, Yok-Ai Que
Background: Phage therapy is being reconsidered as a valuable approach to combat antimicrobial resistance. We recently established a personalized phage therapy pipeline in healthy volunteers, where therapeutic phages were isolated from individuals' skin microbiota. In this study, we aim to validate this pipeline in end-stage heart failure patients supported by left ventricular assist devices (LVADs), focusing on phages targeting , a common pathogen responsible for LVAD infections.
Methods: Over a 2.5-year period, 45 LVAD patients were consistently sampled at their driveline exit sites and foreheads. strains from patients' foreheads were used to amplify patient-specific phages. Newly isolated phages were characterized and tested against isolates (n = 42) from the patient cohort. The virulent phage vB_SepS_BE22, isolated from a patient with a driveline infection, was further tested for its bactericidal activity against biofilms ex vivo with rifampicin on driveline biofilms.
Results: was detected in 32 patients, 3 of whom had driveline infections. Phages were isolated from 8 patients, 6 of which were unique and exhibited narrow host ranges, infecting 19%-52% of strains. vB_SepS_BE22, isolated from patient ID25's microbiota, was the only phage that specifically killed clones linked to a patient's infection. vB_SepS_BE22 also reduced bacterial loads in exponential and stationary phase cultures, as well as in biofilms on drivelines when combined with rifampicin.
Conclusions: This study validated a personalized phage therapy approach, where phages from a patient's own microbiota can be used in chronic infection settings as therapeutic agents.
