Combination of Bacteriophages and Antibiotics for Prevention of Vascular Graft Infections-An In Vitro Study.

(1) Background: Implant-associated bacterial infections are usually hard to treat conservatively due to the resistance and tolerance of the pathogens to conventional antimicrobial therapy. Bacterial colonization of vascular grafts may lead to life-threatening conditions such as sepsis. The objective of this study is to evaluate whether conventional antibiotics and bacteriophages can reliably prevent the bacterial colonization of vascular grafts. (2) Methods: Gram-positive and Gram-negative bacterial infections were simulated on samples of woven PET gelatin-impregnated grafts using Staphylococcus aureus and Escherichia coli strains, respectively. The ability to prevent colonization was evaluated for a mixture of broad-spectrum antibiotics, for strictly lytic species-specific bacteriophage strains, and for a combination of both. All the antimicrobial agents were conventionally tested in order to prove the sensitivity of the used bacterial strains. Furthermore, the substances were used in a liquid form or in combination with a fibrin glue. (3) Results: Despite their strictly lytic nature, the application of bacteriophages alone was not enough to protect the graft samples from both bacteria. The singular application of antibiotics, both with and without fibrin glue, showed a protective effect against S. aureus (0 CFU/cm2), but was not sufficient against E. coli without fibrin glue (M = 7.18 × 104 CFU/cm2). In contrast, the application of a combination of antibiotics and phages showed complete eradication of both bacteria after a single inoculation. The fibrin glue hydrogel provided an increased protection against repetitive exposure to S. aureus (p = 0.05). (4) Conclusions: The application of antibacterial combinations of antibiotics and bacteriophages is an effective approach to the prevention of bacteria-induced vascular graft infections in clinical settings.

Bacteriophage Therapy for Critical Infections Related to Cardiothoracic Surgery.

(1) Objective: Bacterial resistance to conventional antibiotic therapy is an increasingly significant worldwide challenge to human health. The objective is to evaluate whether bacteriophage therapy could complement or be a viable alternative to conventional antibiotic therapy in critical cases of bacterial infection related to cardiothoracic surgery. (2) Methods: Since September 2015, eight patients with multi-drug resistant or especially recalcitrant Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli infections were treated with bacteriophage preparations as a therapy of last resort according to Article 37 of the Declaration of Helsinki. Patients had infections associated with immunosuppression after organ transplantation or had infections of vascular grafts, implanted medical devices, and surgical wounds. Individualized phage preparations were administered locally, orally, or via inhalation for different durations depending on the case. All patients remained on conventional antibiotics during bacteriophage treatment. (3) Results: Patients ranged in age from 13 to 66 years old (average 48.5 ± 16.7) with seven males and one female. Eradication of target bacteria was reached in seven of eight patients. No severe adverse side effects were observed. (4) Conclusions: Phage therapy can effectively treat bacterial infections related to cardiothoracic surgery when conventional antibiotic therapy fails.

Vascular Graft Pre-Treatment with Daptomycin Prior to Implantation Prevents Graft Infection with Staphylococcus aureus in an In Vivo Model.

Background: Infection of vascular grafts is a life-threatening complication in cardiovascular surgical procedures. This experimental study tested the efficacy and possible harmful effects of daptomycin pre-treatment in vivo in prevention of vascular graft infection caused by Staphylococcus aureus. Methods: Polyethylene terephthalate (PET) patches (5 × 7 mm) were sewn on the infra-renal abdominal aorta of 32 New Zealand White rabbits. Before implantation, patches either were pre-treated for 15 min with daptomycin in one group (n = 13) or left untreated in the other group (n = 13) before contamination with 100 mcL bacterial solution (1 × 1010 colony-forming units [CFU] per mL). Six animals with uninfected patches without (n = 3) or with (n = 3) daptomycin pre-treatment served as controls. On postoperative day seven, all patches were explanted, washed with phosphate buffered saline, and sonicated to release viable adherent bacteria. The CFUs were quantified and aortic tissues were histologically examined. In addition, bacterial adherence on the patches was analyzed using scanning electron microscopy (SEM). Results: In the daptomycin pre-treatment group, significantly reduced numbers of CFUs on the patches were observed, compared with non-pre-treated patches (3.21 × 102 ± 1.02 × 103 mL-1 vs. 5.18 × 105 ± 1.05 × 106 mL-1; p < 0.001). Peri-vascular abscesses were visible in all rabbits with S. aureus infected patches, whereas no signs of inflammation were found in the daptomycin pre-treatment group or the control groups. Conclusions: Daptomycin showed excellent in vivo antibacterial activity against vascular graft infection caused by S. aureus, compared with non-pre-treated grafts, resulting in a significant reduction in bacterial infection and prevention of abscess formation. No harmful effects of the antibiotic pre-treatment could be observed.

Fibrin glue as a local drug-delivery system for bacteriophage PA5.

Fibrin glue has been used clinically for decades in a wide variety of surgical specialties and is now being investigated as a medium for local, prolonged drug delivery. Effective local delivery of antibacterial substances is important perioperatively in patients with implanted medical devices or postoperatively for deep wounds. However, prolonged local application of antibiotics is often not possible or simply inadequate. Biofilm formation and antibiotic resistance are also major obstacles to antibacterial therapy. In this paper we test the biocompatibility of bacteriophages incorporated within fibrin glue, track the release of bacteriophages from fibrin scaffolds, and measure the antibacterial activity of released bacteriophages. Fibrin glue polymerized in the presence of the PA5 bacteriophage released high titers of bacteriophages during 11 days of incubation in liquid medium. Released PA5 bacteriophages were effective in killing Pseudomonas aeruginosa PA01. Overall, our results show that fibrin glue can be used for sustained delivery of bacteriophages and this strategy holds promise for many antibacterial applications.

Renal artery revascularization by using the Riolan anastomosis as feeding vessel in a patient with abdominal aortic coarctation due to fibromuscular dysplasia.

Fibromuscular dysplasia is a non-inflammatory, non-atherosclerotic vascular disease, occurring predominantly in younger females. A histologically heterogeneous group of fibroplasia without an inflammatory component causes arterial narrowing. It affects mostly one or both renal arteries, cervicocranial or visceral arteries, leading to hypertension, renal failure/renal infarction or stroke/transient ischaemic attack. We present the case of a young female patient with abdominal aortic coarctation, history of acute renal failure, and critical hypertension due to pseudo-occlusion of both renal arteries. We performed renal artery revascularization specifically by using the Riolan anastomosis as feeding vessel.