Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/wPLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.

New Mechanistic Insights into Purine Biosynthesis with Second Messenger c-di-AMP in Relation to Biofilm-Related Persistent Methicillin-Resistant Staphylococcus aureus Infections

Persistent endovascular infections caused by MRSA, including vascular graft infection syndromes and infective endocarditis, are significant and growing public health threats. A particularly worrisome trend is that most MRSA isolates from these patients are “susceptible” in vitro to conventional anti-MRSA antibiotics, such as VAN and daptomycin (DAP), based on Clinical and Laboratory Standards Institute breakpoints.

Expanded access use of rezafungin for salvage therapy of invasive Candida glabrata infection: A case report

Rezafungin is a semi-synthetic, long acting echinocandin with broad spectrum activity against many Candida species (spp)., and Aspergillus spp., including subset of drug-resistant strains. It is currently in phase III trials and was found to be safe and effective for treatment of candidemia and/or invasive Candida infections in a phase II trial. However, there are no long-term safety or efficacy data. We report on the successful ongoing compassionate use of rezafungin obtained through expanded access for over one year in a patient with a multidrug-resistant Candida glabrata mediastinal infection from a vascular graft infection and retained foreign material.

Vascular graft infection in the aortoiliac territory – our view in the light of European Society for Vascular Surgery Guidelines − the retrospective observation study

Introduction: Vascular graft infection in the aortoiliac territory (abdominal VGI) is undoubtedly one of the most serious complications in vascular surgery. The treatment is burdened with high mortality and morbidity rates. In 2020, the Guidelines on the Management of Vascular Graft and Endograft Infections were published by the European Society for Vascular Surgery (ESVS). In the light of these guidelines, we decided to review retrospectively all patients who presented to our institution with abdominal VGI. Methods: Retrospective observational study of patients presented with abdominal VGI treated in our institution between 2011−2019 (9 years). The primary goal was to elucidate the rate of vascular graft infection in aortoiliac reconstructions performed between 2011−2019 and also the mortality rate in the patient cohort operated for this complication. The secondary goals were to evaluate the success rate and the complication rate in different types of reconstructions. Results: In the defined period between 2011−2019 we performed 363 open aortoiliac reconstructions. During the same period we treated altogether 15 patients with abdominal VGI, whose primary reconstruction was mostly performed before 2011 (11 patients). In our cohort of patients who underwent reconstruction between 2011−2019 we observed a graft infection only in 4 cases (1.1%). In the group of 15 patients with abdominal VGI, the male gender prevailed (14 patients). The mean age at the time of primary reconstruction was 61 years. Most of our reconstructions were performed for occlusive disease (14 cases). All infected grafts were aortobifemoral (1 unilateral aortofemoral). They were all late infections with an average presentation time of 61 months since the primary reconstruction (15−180 months). Early mortality rate was as high as 27% (4 patients) and overall mortality was 40%. The secondary reinfection rate after primary treatment was 33%. Conclusion: Treatment of abdominal VGI is still burdened with high mortality and morbidity rates. The current ESVS guidelines provide valuable guidance for the diagnosis and management of VGI. It nevertheless remains obvious that the treatment needs to be tailored individually in a multidisciplinary team environment.

Outpatient parenteral antimicrobial therapy (OPAT) for aortic vascular graft infection; a five-year retrospective evaluation

Objectives An estimated 1% of endovascular aneurysm repair (EVAR) devices become infected, carrying a high mortality rate. Surgical explantation is recommended and prognosis is guarded. This retrospective cohort analysis focuses on the role of outpatient parenteral antimicrobial therapy (OPAT) in the management of aortic vascular graft infections following EVAR. Methods Patients who received OPAT for aortic graft infections (AGI) following EVAR from 2014 to 2018 inclusive were identified using the OPAT database. Clinical, microbiological and radiological data were collected. Survivors were followed up for a median of 36 months (range 25–60) after first presentation with infection. Outcomes were assessed. Results Eleven cases with 20 OPAT episodes were identified: 10/11 male, median age 76 (IQR 71–81). Median time to presentation was 7 months (range 0–81 months) after EVAR. OPAT lead to a 55% reduction in length of hospital stay. One patient had graft explantation; four others had temporising measures. Eight of 11 were alive a median of 36 months after presentation with infection, having had a median of 2 re-treatments on OPAT (range 1–3). Seven of the eight survivors were on continuous suppressive oral antimicrobials; three were also intermittently on intravenous antibiotics for flares of infection. Patient/ infection outcomes were cure (1/11), improved (7/11), failure (3/11). Conclusion AGI following EVAR usually presents in the first year after graft deployment. OPAT has an important peri-operative role in patients suitable for curative surgery. OPAT followed by oral suppressive antimicrobial therapy can be a feasible long-term treatment for non-curative management of AGI. Survival in our cohort was longer than expected, and OPAT was feasible despite the complexity of these infections. OPAT can avoid multiple and lengthy hospital admissions and maximise time at home and quality of life in this cohort with life-limiting infection.