Successful Treatment of a Chronically Infected and Occluded Aorto-Bifemoral Dacron ® Bypass with Bacteriophages

Successful Treatment of a Chronically Infected and Occluded Aorto-Bifemoral Dacron ® Bypass with Bacteriophages. Biomed J Sci & Tech Res


Background
In vascular surgery, infections of the vascular grafts are considered to be severe complications [1]. Especially infections of aortic grafts are associated with a high morbidity and mortality of up to 75 % [2]. Since these procedures are often performed in patients with multiple comorbidities, the required explantation of the infected graft and the extensive struggle with the related abdominal infection is related with an early postoperative morbidity and mortality of even over 20 % [3]. Despite the initial achievement of a successful treatment, the general rate of reinfection can be up to 20 % of cases [4]. This is mainly due to bacterial colonies embedded in the peri-prosthetic tissue, which then form a surface-adherent biofilm and hence have an up to 1000-fold greater resistance to antibiotic administration [5]. Even a targeted antibiosis appropriate to antimicrobial susceptibility testing can only suppress a graft infection but does not constitute a curative treatment option [6]. The most common pathogenic bacteria associated with graft inflammation are Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci, Enterobacterales, Pseudomonas aeruginosa and corynebacteria [7]. These bacteria regularly enhance their specific virulence by attaching to the prosthetic material, and hence averting the local immune response by forming biofilms, that hinder

Discussion
This case demonstrates a successful treatment of a chronically infected occluded aorto-bifemoral Dacron ® bypass by a local bacteriophage application. It is assumed that around 50-65% of prosthesis infections are a result of bacterial contamination during surgery [7][8][9][10]. A general distinction is made between early (up to 30 days postoperatively) and late infections, although the classification is arbitrary [7,10,11]. Early prosthesis infections are often assumed to be a consequence of intraoperative contamination and late infections to be a result of hematogenous bacterial spread, but profound evidence for this is limited. Late infections are usually caused by insufficient tissue integration of the prosthesis into the graft bed. Common pathogenic agents are staphylococci, enterobacteria and corynebacteria [7,10]. Bacteriophages (or simply 'phages'; Greek: "bacteria eater") are viruses that selectively infect bacterial cells and were first described in 1917 by the Canadian Félix Hubert d'Hérelle [12].
Currently Bacteriophages are known as a potent anti-bacterial treatment due to their lytic activity [13]. They are considerably stable when exposed to the inflammatory environment and contribute significantly to the regulation of global bacterial mass.
A bacteriophage can only multiply where its host is. They are highly specific and therefore predominantly affect strains within one bacterial species, rarely crossing species boundaries [14].
In the first (lytic) cycle of viral reproduction, phages kill their corresponding bacteria through lysis: once infected, the bacterium host cell then starts the process of reproduction, the destruction of the bacterium, and the release of new phage particles; this process is controlled by enzymes and an interaction of bacterial and phage genes. In the second (lysogenic) cycle, the bacteriophage nucleic acid is integrated into the host bacterium's genome or forms a circular replicon in the bacterial cytoplasm. Compared to other antibacterial therapeutic strategies like local Rifampine treatment [6], no cytotoxic effects on vascular cells could be found for bacteriophages [15].
In addition, they are effective on multi-drug resistant bacteria as well as biofilm-organized bacteria. Recently, in a case series of eight patients with infections of vascular grafts, surgical wounds or implanted medical devices further demonstrated the feasibility of using different bacteriophages with lytic activity for successful treatment of bacterial infections [16]. Although bacteriophages were used for successful treatment of infections of vascular implants, bacteriophage treatment is still not common and not an officially recommended option for infections in the westernized hemisphere [17]. The retro-and intraabdominal application of phages directly to the infection site ensured a maximum concentration, contact time and invasion of the bacteriophages into the infected peri graft tissue. We were able to perform a short operation time, a definite treatment in respect to complete skin/wound closure and the forego of any drainages. No bacteriophage related clinical adverse events had been detected in our case. A three-month follow-up PET-CT scan revealed no signs of infections. It could be assumed that the bacteriophage treatment was successful.
In order to treat the local inflammation in the abdominal and femoral areas in the long term intra-and postoperatively, we perceived the use of bacteriophages as an alternative therapy option in antibacterial local therapy. However, there is an ongoing follow-up for the patient to assure a lasting treatment success.
In summary, this case report demonstrates that bacteriophage treatment could be a curative treatment option for patients with bacterial graft-and peri graft infections that are not suitable for extensive surgical approaches.