Treatment of an Infected TEVAR with Extra- and Endovascular Bacteriophage Application.

Introduction: Graft infections are severe complications. Surgical resection of infected aortic stent grafts is associated with high mortality and morbidity. Therefore, alternatives or adjuncts to antibiotic treatment and extensive surgery are urgently needed. Report: A 67 year old woman was admitted with a methicillin sensitive Staphylococcus aureus infected stent graft in the thoracic aorta. Local infection was confirmed by PET-CT imaging. Surgical resection of the stent graft was not feasible because of comorbidities. Therefore, a three step approach for local bacteriophage treatment was performed as a last resort treatment. Firstly, the para-aortic tissue was debrided via left thoracotomy, a bacteriophage suspension was applied on the outer surface of the aorta, and a vacuum irrigation system was installed. After repeated alternating instillation of the bacteriophage suspension for three days, as a second step, the vacuum sponges were removed and a bacteriophage containing gel was applied locally on the outer surface of the aorta. In the third step, the bacteriophage containing gel was applied to a thoracic stent graft, which in turn was placed endovascularly into the infected stent. Discussion: After 28 days, the patient was discharged from hospital with normalised infection parameters. PET-CT imaging at three and 12 months post-intervention did not show signs of infection in or around the thoracic aorta. This Case demonstrates successful treatment of an infected endovascular stent graft by application of bacteriophages both to extravascular and, as a novel approach, endovascular sites using a bacteriophage coated stent graft.

Bacteriophage-Enriched Galenic for Intrapericardial Ventricular Assist Device Infection.

We report a case of severe outflow graft infection following left ventricular assist device (LVAD) implantation. A 51-year old male LVAD patient was readmitted to our hospital presenting signs of systemic infection. One year previously, LVAD implantation (HeartMate3, Abbott, Chicago, IL, USA) with concomitant patent foramen ovale closure had been performed in the context of end-stage heart failure due to dilative cardiomyopathy (INTERMACS III). The indication for LVAD-therapy was bridge-to-candidacy, since the patient did not instantly fulfill all criteria for cardiac transplantation. At admission, a PET-CT scan unveiled fluid accumulation, encircling the outflow-graft prosthesis (SUVmax 10.5) with contrast-enhancement involving the intrathoracic driveline (SUVmax 11.2). Since cardiac transplantation was not feasible, the patient underwent surgical revision. In the first step, redo sternotomy was performed with local debridement, including jet lavage. Intraoperative swabs confirmed bacterial infection with staphylococcus aureus. Following this, the patient underwent negative pressure wound therapy (NPWT) with instillation using the V.A.C. VERAFLO system (KCI-3M, San Antonio, TX, USA) for a total of 19 days. Due to the severity of infection, local bacteriophage application was performed within the wound closure. In order to concentrate phage therapy at the infection site, phages were applied using a novel semi-fluid galenic. After wound closure, the patient was discharged with an uneventful course. A control PET-CT scan 3 months after discharge showed a significant decrease in infection (outflow graft: SUVmax 7.2, intrathoracic driveline: SUVmax 3.0) correlated with contrast enhancement. Bacterial infection of intrathoracic VAD components represents a severe and potentially life-threatening complication. If cardiac transplantation is not feasible, complex wound management strategies are required. Local bacteriophage therapy might be a promising addition to already established therapeutical options. In order to improve bacteriophage retention at the wound site, application of a viscous galenic might be beneficial.

Bacteriophages for the Treatment of Graft Infections in Cardiovascular Medicine.

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections.