Novel bacteriophage therapy for treatment of left ventricular assist device infection

Abstract

Purpose Bacteriophages are lytic viruses that are specific for their bacterial hosts and do not infect human cells. Bacteriophages can penetrate biofilm and lyse biofilm-based bacteria. We describe the use of bacteriophage therapy (BT) as an adjunct to intravenous (IV) antibiotics in 2 cases of refractory ventricular assist device (VAD) infections. Methods BT products active in vitro against the patients’ isolates were identified. We obtained approval from the Food and Drug Administration (eIND #18133 and eIND #17819) to use BT as adjunctive treatment; informed consent was obtained. Results Table 1 describes the 2 VAD infection cases in detail. Each patient received BT as outpatient parental therapy without adverse events. Case 1 had negative sternal wound cultures for MSSA at end of therapy. Case 2 developed Pseudomonas aeruginosa (PsA) bacteremia while on BT that resolved with a change in antibiotics. Bacteremic isolates from case 2 during BT remained susceptible to all 3 lytic phages; molecular sequencing confirmed that these PsA isolates were the same as at the start of therapy. In Case 2, serum neutralizing activity emerged during therapy resulting in reduction in viable phage titers in vitro. Each patient went on to successful heart transplantation. Conclusion We describe early experience using BT for treatment of biofilm-based VAD infections. BT was well tolerated. The potential relevance of serum neutralizing activity to the antimicrobial impact of BT during treatment warrants further investigation.