Veronica Stuckey

Background:  Vascular graft infections (VGIs) present an uncommon (1-3%) but potentially deadly (mortality 20-30%) post-surgical adverse effect. VGIs are biofilm associated infections resistant to antibiotic treatment due to difficulty penetrating the biofilm microenvironment[1]. Patients within the first 4 months post-operatively are at the highest risk of infections from bacteria such as S. aureus, E. Coli, Pseudomonas, Klebsiella, Proteus spp. and potentially a combination thereof[2]. Current methods of treating VGIs after antibiotic failure, such as surgical debridement, graft removal and replacement, may not be suitable for many patients with contraindicated co-morbidities, leaving many without options[3]. Current research suggests an alternative means of preventing and eliminating biofilm formation, namely lytic bacteriophages, as a viable solution to a growing antibiotic resistance epidemic[4].

Methods: PubMed searches included the terms: “vascular graft,” “bacteriophage,” “material,” and “biofilm” within the past 5 years.

Results: In recent years, a rapidly expanding base of literature suggests further research in phage therapy is warranted[5]. Biofilm prevention can take many forms, progressively increasing in complexity. The first begins with material choice; one study proved the significance of material choice in preventing bacterial adhesion and growth by comparing nine graft materials, demonstrating superior bioburden resistance by Dacron-Silver-Triclosan and Omniflow-II[6]. Secondly, research into optimal sustained phage delivery points to embedded fibrin glue as a promising method, demonstrating improved antibacterial activity over liquid delivery methods[7]. Next, in-vitro studies show combined administration of phages and antibiotics completely inhibit growth in both gram-positive (S. aureus) and gram-negative (E. Coli) species, as opposed to either individually[8]. Finally, a case study in a 67-year-old female with MSSA infection of a thoracic aorta graft suggests efficacy in-vivo with 12-month resolution post-administration of a gel-based bacteriophage cocktail (SniPha360) in combination with systemic antibiotics flucloxacillin and cefuroxime[9].

Conclusions: Bacteriophage application may be a potential last-line therapy for patients that have exhausted conventional antibiotic treatment and are not surgical candidates. A literature review including 37 patients with persistent vascular prothesis infection showed 70.3% with clinical resolution, 10.8% with improvement and 18.9% with no improvement after phage therapy. In addition, no adverse effects directly related to phage usage were reported[10]. Given the growing literature indicating positive safety and efficacy of phage treatment, future directions in phage therapy may include expanding efforts to identify and genotype wild bacteriophages, inducing bacteriophage mutations targeting drug resistant bacteria, and standardizing methods, guidelines and protocols in phage research [5].

Works Cited:

1. Wilson WR, Bower TC, Creager MA, et al. Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association. Circulation. 2016;134(20):e412-e460. doi:10.1161/CIR.0000000000000457
2. Gharamti A, Kanafani ZA. Vascular Graft Infections: An update. Infect Dis Clin North Am. 2018;32(4):789-809. doi:10.1016/j.idc.2018.06.003
3. Wouthuyzen-Bakker M, van Oosten M, Bierman W, et al. Diagnosis and treatment of vascular graft and endograft infections: a structured clinical approach. Int J Infect Dis. 2023;126:22-27. doi:10.1016/j.ijid.2022.11.011
4. Adesanya, Oluwafolajimi & Oduselu, Tolulope & Akin-Ajani, Oluwawapelumi & Adewumi, Moses Olubusuyi & Ademowo, Olusegun. (2020). An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance. AIMS Microbiology. 6. 10.3934/microbiol.2020014.
5. Strathdee SA, Hatfull GF, Mutalik VK, Schooley RT. Phage therapy: From biological mechanisms to future directions. Cell. 2023;186(1):17-31. doi:10.1016/j.cell.2022.11.017
6. Tello-Díaz C, Palau M, Muñoz E, et al. Methicillin-Susceptible Staphylococcus aureus Biofilm Formation on Vascular Grafts: an In Vitro Study. Microbiol Spectr. Published online February 7, 2023. doi:10.1128/spectrum.03931-22
7. Rubalskii E, Ruemke S, Salmoukas C, et al. Fibrin glue as a local drug-delivery system for bacteriophage PA5. Sci Rep. 2019;9(1):2091. Published 2019 Feb 14. doi:10.1038/s41598-018-38318-4
8. Ruemke S, Rubalskii E, Salmoukas C, et al. Combination of Bacteriophages and Antibiotics for Prevention of Vascular Graft Infections-An In Vitro Study. Pharmaceuticals (Basel). 2023;16(5):744. Published 2023 May 13. doi:10.3390/ph16050744
9. Grambow E, Junghans S, Kröger JC, Reisinger EC, Krause BJ, Groß J. Treatment of an Infected TEVAR with Extra- and Endovascular Bacteriophage Application. EJVES Vasc Forum. 2022;56:20-23. Published 2022 Feb 16. doi:10.1016/j.ejvsvf.2022.02.004
10. Simpson EA, MacLeod CS, Stacey HJ, Nagy J, Jones JD. The Safety and Efficacy of Phage Therapy for Infections in Cardiac and Peripheral Vascular Surgery: A Systematic Review. Antibiotics (Basel). 2023;12(12):1684. Published 2023 Nov 30. doi:10.3390/antibiotics12121684