Bacteriophage Therapy for Treatment of a Multi-Drug Resistant VAD-Specific Infection in a Pediatric Patient

Abstract

<h3>Introduction</h3> Ventricular assist device (VAD) driveline infections are a source of significant morbidity and recurrence can result in multi-drug resistant infections (MDRIs). Bacteriophage (BP) therapy has been successfully used for MDRIs, but it has not been described in a pediatric VAD-specific MDRI. We present the case of BP therapy used for the control of a <i>Klebsiella pneumoniae</i> VAD-specific MDRI in a pediatric patient. <h3>Case Report</h3> A 10 y/o highly sensitized male with a HeartWare HVAD™ (Medtronic, Fridley, MN) in place for heart failure secondary to congenital heart disease developed a MDR <i>K. pneumoniae</i> VAD pump pocket and deep driveline infection. He underwent debridement, creation of fistulous tract for additional drainage, and prolonged IV antibiotic therapy (including extended infusions of meropenem). He continued to have purulent drainage from his fistulous tract, intermittent fevers, and evidence of worsening infection on serial imaging. Fifteen months after the infection was identified, he developed worsening heart failure and concern for pump thrombosis prompting plans for device exchange. Given the high risk of infection of the new VAD, BP therapy was developed (TAILOR, Baylor College of Medicine, Houston, TX) and administered under an emergency Investigational New Drug application with the US Food and Drug Administration. After 4 days of systemic BP therapy he underwent VAD explant to extracorporeal membrane oxygenation (ECMO) support followed by serial mediastinal washouts with antibiotic and local BP application prior to placement of the new VAD. He completed a 6 week course of systemic BP with ongoing meropenem therapy. No adverse reactions associated with BP were observed. He subsequently underwent heart transplant on day 37 of 42 of BP therapy when a donor organ became available. No evidence of mediastinitis was observed intra-operatively at time of transplant; cultures and PCRs from the mediastinal tissue were negative. He is now 6 months post-transplant without any evidence of infection recurrence. <h3>Summary</h3> Bacteriophage played a significant role in the eradication of a VAD-specific MDRI in a pediatric patient. This may represent a safe and effective therapy for device-related MDRIs refractory to antibiotic and surgical therapy in pediatric patients.