Targeting Chronic Biofilm Infections With Patient-derived Phages: An In Vitro and Ex Vivo Proof-of-concept Study in Patients With Left Ventricular Assist Devices.

Abstract

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 Staphylococcus epidermidis, 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. S epidermidis strains from patients' foreheads were used to amplify patient-specific phages. Newly isolated phages were characterized and tested against S epidermidis 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 S epidermidis biofilms ex vivo with rifampicin on driveline biofilms.

Results: S epidermidis 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 S epidermidis strains. vB_SepS_BE22, isolated from patient ID25's microbiota, was the only phage that specifically killed S epidermidis 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.