Efficacy of boric acid used to treat experimental vascular graft infection by methicillin-resistant Staphylococcus aureus.

INTRODUCTION: We aimed to investigate the efficacy of local boric acid (BA) and teicoplanin in prosthetic vascular graft infection (PVGI) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a rat model. METHODOLOGY: Fourty rats were divided into five groups. Group 1 received no treatments (control group); group 2 was uncontaminated polytetrafluoroethylene (PTFE) graft group; group 3 was untreated and the PTFE graft was contaminated with 2×107 CFU/mL MRSA; group 4 received local BA (8 mg/kg) and was contaminated with with 2×107 CFU/mL MRSA; group 5 received local BA (8 mg/kg) and intraperitoneal teikoplanin (10 mg/kg), and was contaminated with 2×107 CFU/mL MRSA; On the 3rd day, grafts and serums were removed for microbiological, histological and serological tests. RESULTS: The amounts of culture growth in groups 4 and 5 were significantly lower compared to group 3 (p < 0.001). TNF-α was significantly higher in Group 3 than the other groups (p = 0.001). There was no significant difference between the groups in serum IL-1 levels (p = 0.138). Monocyte chemotactic protein-1 (MCP-1) was not significantly different between groups 3, 4, and 5, but it was significantly higher than groups 1 and 2 (p < 0.001). The severity of inflammation was significantly higher in group 3 than the other groups, and fibroblastic proliferation, granulation tissue and collagen synthesis were significantly lower (p < 0.05). CONCLUSIONS: Our study showed that local BA and combined teicoplanin treatment is effective in preventing PVGI.

Editor's Choice - Validation of the Management of Aortic Graft Infection Collaboration (MAGIC) Criteria for the Diagnosis of Vascular Graft/Endograft Infection: Results from the Prospective Vascular Graft Cohort Study.

OBJECTIVE: The timely management of vascular graft/endograft infection (VGEI) is crucial to a favourable outcome, yet can be challenging as there is no validated gold standard diagnostic test. Recently, a new case definition has been proposed by the Management of Aortic Graft Infection Collaboration (MAGIC) to close the diagnostic gap. The aim of this study was to validate the MAGIC criteria as a suggested diagnostic standard for the diagnosis of suspected VGEI in the prospective Vascular Graft Cohort study (VASGRA). METHODS: VASGRA is an open, prospective, observational cohort study. Prospective participants in VASGRA between 2013 and 2019 were included (257 patients; 137 with VGEI). The accuracy of the MAGIC criteria for a diagnosis of VGEI was evaluated retrospectively by calculating the sensitivity and specificity vs. the consensually adjudicated VASGRA infection status. RESULTS: The VASGRA cohort categorised 137 (53.3%) patients as "diseased" and 120 patients as "not diseased"; using the MAGIC criteria, 183/257 (71.2%) patients were considered to be "diseased". Thus, for the MAGIC criteria, a sensitivity of 99% (95% confidence interval [CI] 96-100) and a specificity of 61% (95% CI 52-70) were calculated. Considering suspected VGEI according to the MAGIC criteria as "not diseased" achieved congruent assessments of the VASGRA team and the MAGIC criteria, with a sensitivity of 93% and a specificity of 93%. The accuracy of the MAGIC criteria for the different graft locations were also compared. If the suspected VGEIs were assigned to the "not diseased" group, VGEIs of the thoracic aorta seemed to have a poorer sensitivity (86%; 95% CI 73-95) than the other graft locations. CONCLUSION: The current MAGIC criteria offer good sensitivity and specificity in the context of true infections but a reduced specificity for a possible VGEI.

Pre-clinical in vivo Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) remains an important complication with a high mortality and morbidity rate. Currently, studies focusing on the role of vascular graft coatings in the prevention of VGI are scarce. Therefore, the aims of this study were to survey and summarise key features of pre-clinical in vivo models that have been used to investigate coating strategies to prevent VGI and to set up an ideal model that can be used in future preclinical research. DATA SOURCES: A systematic review was conducted in accordance with the Preferred reporting items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in MEDLINE (PubMed), Embase, and Web of Science. REVIEW METHODS: For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). The type of animal model, graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 94 papers focusing on in vivo testing were included. Staphylococcus aureus was the organism most used (n = 65; 67.7%). Most of the graft types were polyester grafts. Rifampicin was the most frequently used antibiotic coating (n = 43, 48.3%). In the outcome assessment, most studies mentioned colony forming unit count (n = 88; 91.7%) and clinical outcome (n = 72; 75%). According to the ToxRTool, 21 (22.3%, n = 21/94) studies were considered to be not reliable. CONCLUSION: Currently published in vivo models are very miscellaneous. More attention should be paid to the methodology of these pre-clinical reports when transferring novel graft coatings into clinical practice. Variables used in pre-clinical reports (bacterial strain, duration of activity coating) do not correspond well to current clinical studies. Based on the results of this review, a proposal for a complete and comprehensive set up for pre-clinical invivo testing of anti-infectious properties of vascular graft coatings was defined.

Does washing medical devices before and after use decrease bacterial contamination?: An in vitro study.

ABSTRACT: Surface treatment of medical devices may be a way of avoiding the need for replacement of these devices and the comorbidities associated with infection. The aim of this study was to evaluate whether pre- and postcontamination washing of 2 prostheses with different textures can decrease bacterial contamination.The following microorganisms were evaluated: Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis and Enterococcus faecalis. Silicone and expanded polytetrafluoroethylene vascular prostheses were used and divided into 3 groups: prostheses contaminated; prostheses contaminated and treated before contamination; and prostheses contaminated and treated after contamination. Treatments were performed with antibiotic solution, chlorhexidine and lidocaine. After one week of incubation, the prostheses were sown in culture medium, which was incubated for 48 hours. The area of colony formation was evaluated by fractal dimension, an image analysis tool.The antibiotic solution inhibited the growth of S epidermidis and chlorhexidine decrease in 53% the colonization density for S aureus in for both prostheses in the pre-washing. In postcontamination washing, the antibiotic solution inhibited the growth of all bacteria evaluated; there was a 60% decrease in the colonization density of S aureus and absence of colonization for E faecalis with chlorhexidine; and lidocaine inhibited the growth of S aureus in both prostheses.Antibiotic solution showed the highest efficiency in inhibiting bacterial growth, especially for S epidermidis, in both washings. Lidocaine was able to reduce colonization by S aureus in post-contamination washing, showing that it can be used as an alternative adjuvant treatment in these cases.

[18F-fluorodeoxyglucose PET/CT in the diagnosis of vascular graft infection]. / Vozmozhnosti PET/KT S 18F-ftordezoksiglyukozoi v diagnostike infektsii sosudistykh protezov.

OBJECTIVE: To investigate diagnostic role of 18F-fluorodeoxyglucose PET/CT in patients with suspected vascular graft (VG) infection. MATERIAL AND METHODS: A prospective analysis included data of 30 PET/CT examinations for suspected infection of aortic VG (n=27) and bypass grafts (n=3) after surgical treatment (median 48 months). In 77% (23/30) of cases, the diagnosis was initially «possible¼ (n=11) or «rejected¼ (n=12) in accordance with common diagnostic criteria. All PET/CT results were verified by clinical, laboratory and intraoperative («=20) data. VG infection was confirmed in 18 patients and ruled out in 12 cases. RESULTS: PET/CT confirmed VG infection in 94% (17/18) and excluded in 50% (6/12) of cases. False PET/CT results were obtained in 23% (7/30) cases: false positive in 6 cases and false negative in 1 case. Thus, sensitivity, specificity and diagnostic accuracy of PET/CT were 94%, 50% and 77%, respectively; positive and negative predictive value - 74% and 86%. PET/CT results allowed correct reclassifying 33% (10/30) of cases. VG infection was confirmed in 73% (8/11) of patients with initially «possible¼ diagnosis and excluded in 17% (2/12) of patients with initially «rejected¼ infection. Moreover, whole body PET/CT revealed unknown inflammation foci outside VG in 73% (22/30) of cases. These data were applied to correct treatment approach in 80% (24/30) of cases. CONCLUSION: Our results showed high efficacy of 18F-fluorodeoxyglucose PET/CT in the diagnosis of VG infection. Despite low specificity, this technique has high sensitivity and accuracy that allowed reclassifying 33% of cases.

Management of Vascular Infections in Low- and Middle-Income Countries.

Background: Vascular infections are rare and challenging conditions with significant deaths and morbidity. Their management necessitates a multi-disciplinary approach and substantial human and financial resources. The management selected may be influenced by the available resources in low- and middle-income countries (LMICs), where such resources may be variable. Methods: We reviewed the published literature and reviewed the management options for various vascular infections with a focus on carotid, aortic, infrainguinal, and dialysis access infections. Results: Recommendations related to prevention and treatment will be offered from the perspective of LMICs. The general principles for prevention are in compliance with established surgical site infection guidelines and minimize the use of prosthetic material. Early detection and intervention by removing all infected prosthetic material, debridement, drainage, and coverage of the infected field with vascularized tissue are essential steps in the management of the infection. Revascularization using an extra-anatomic or in situ approach is individualized based on the resources and expertise available. Conclusions: The prevention and management of vascular infections in LMICs are effective by adhering to time-proven principles even with limited resources.

99mTC-white blood cell scintigraphy with SPECT/CT in the diagnosis of vascular graft infection. / Gammagrafía con leucocitos marcados y SPECT/TC en el diagnóstico de infección de prótesis vasculares.

AIM: Vascular graft infection is a rare complication with a high morbidity and mortality. Early diagnosis is essential to establish an adequate treatment. We assess the accuracy of 99mTc-WBC scintigraphy with SPECT/CT in the diagnosis of vascular graft infection. MATERIALS AND METHODS: We retrospectively analyzed thirty 99mTc-WBC scintigraphies with SPECT/CT performed in thirty patients with suspicion of vascular prosthesis infection. Studies were considered positive for graft infection if the intensity of activity involving the graft was greater than the liver or bone marrow activity (spine and pelvis). RESULTS: Final diagnosis of infection was established in 10 patients, based on Fitzgerald criteria. Scintigraphy was positive in 11 patients. No false negatives were obtained. The values of sensitivity and specificity were 100% and 95%, respectively, with a PPV of 91% and a NPV of 100%. Twenty five patients had a CT performed prior to scintigraphy, in 9 cases the result was positive and in the remaining 16 was negative. CT sensitivity and specificity obtained in our study were 62.5% and 76% respectively, with a PPV of 55.6% and a NPV of 81.3%. Diagnosis of infection led to prosthesis exeresis in 8 cases (all of them had a positive microbiological study of the extracted material), while the remaining 2 patients were treated with antibiotic therapy alone due to high surgical risk. CONCLUSION: Our results suggest a high accuracy for 99mTc-WBC scintigraphy with SPECT/CT in the assessment of clinically suspected arterial graft infection.

[Fever and persisting calf abscess ten years after aorta-bifemoral bypass]. / Koorts en een kuitabces door geïnfecteerde aortaprothese.

A 52-year-old woman presented with fever and a persisting calf abscess ten years after she had received an aorta-bifemoral bypass. Her infection parameters were increased and she had anaemia. CT of the abdomen revealed air surrounding the proximal anastomosis of the bypass suggesting bypass graft infection. The diagnosis of an aorta-duodenal fistula was confirmed by gastroduodenoscopy showing migration of the bypass through the wall of the duodenum into the intestinal lumen. The bypass was resected and reconstructed using the superficial femoral vein. The patient recovered uneventful.

Aortobronchial fistula and Listeria endograft infection after repeated T/EVAR: a rare combination.

Here we present a rare combination of aortobronchial fistula and Listeria endograft infection after repeat endovascular aortic repair. Device retention, debridement and negative pressure wound therapy, in combination with suppressive antimicrobial therapy, led to satisfactory control of infection until the patient died due to another complication. The combination of an aortobronchial fistula and Listeria endograft infection has never been described before. This present case should encourage and show clinicians the importance of an interdisciplinary approach in highly difficult clinical courses.

Persistent Coxiella burnetii cardiovascular infection on Bentall-De Bono prosthesis.

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended.

Successful long-term antibiotic suppressive therapy in a case of prosthetic valve endocarditis and a case of extensive aortic and subclavian graft infection.

INTRODUCTION: The indication for surgical valve replacement in cases of infective endocarditis is well defined in current guidelines. However, some patients are not fit or willing to undergo major surgical procedures. Interestingly, to the best of our knowledge, there is scarce information in the literature on how to deal with such cases and what might be the outcome. CASE REPORT: We present two complicated cases of prosthetic infective endocarditis with definite indication for replacement of involved foreign material, who were treated successfully with long-term suppressive antibiotic therapy. CONCLUSION: These two cases demonstrate that individualized long-term antibiotic suppressive therapy might be effective in selected patients with complicated PVE unfit or unwilling to undergo high-risk cardiothoracic surgical interventions.

Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections.

OBJECTIVES: This study aims to evaluate the effects of mesenchymal stem cell (MSC) implantation on vascular graft infections caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and compare with antibiotic treatment. MATERIALS AND METHODS: Healthy adult 56 Wistar rats (age, over 5 months; weighing, 300-350 g) were divided into eight groups. Group 1 was defined as the control group and group 2 was defined as the infected control group. Groups 3 and 4 were defined as Dacron grafted and MRSE infected groups, treated with tigecycline and MSCs, respectively. Groups 5 and 6 were performed polytetrafluoroethylene (PTFE) graft and infected with MRSE. These groups were also administered tigecycline and MSC treatment, respectively. Groups 7 and 8 were infected with MRSE without graft administration and were also performed tigecycline and MSC treatment, respectively. Grafts and soft tissue specimens were collected at 13 days postoperatively. Colony counts of peri-graft tissue were performed. All samples were evaluated by enzyme-linked immunosorbent assay (ELISA) for the markers that determine stem cell activity. RESULTS: The overall success of the treatments was assessed by the number of rats with MRSE recurrence, regardless of graft used. The difference between the untreated group 2, tigecycline groups (3, 5 and 7) and MSCs groups (4, 6 and 8) were statistically significant. Success of MSC and tigecycline treatments was similar in Dacron, PTFE, and non-grafted groups. There was a resistance of MRSE infection in Dacron groups to MSC and tigecycline treatments. This was considered to be indicative of the susceptibility of the Dacron grafts to infection. However, there was no significant difference between group 2 and Dacron groups in terms of bacterial colonization. ELISA results were significant in three cytokines. CONCLUSION: Mesenchymal stem cells can be considered as an alternative treatment option on its own or part of a combination therapy for control of vascular graft infections.

Management of abdominal aortic prosthetic graft and endograft infections. A multidisciplinary update.

Abdominal aortic graft infections (AGIs) occur in 1-5% of aortic prosthetic placements. It can result in limb amputation, pseudo-aneurysm formation, septic emboli, aorto-enteric fistulae, septic shock and death. The most frequently involved pathogens are methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, followed by Enterobacteriaceae and uncommon bacteria. In case of gut involvement the presence of fungi has to be considered. Computed tomography angiography is actually the gold standard diagnostic imaging but magnetic resonance is a valid alternative. Nuclear medicine imaging is commonly used to improve sensitivity and specificity. Signs and symptoms are often aspecific and blood cultures can be negative, requiring alternative ways to detect the microorganism responsible for infection, such as 16S rRNA gene sequencing and molecular rapid diagnostic tests. Curative surgical intervention is the first choice approach, with in-situ reconstruction providing by far the best outcome and xenopericardial bovine patch as a promising option. For patients unable to undergo major surgery, the outcome of conservative approach remains uncertain but usually provides for life-long suppressive therapy. However, in selected cases an attempt of stopping antibiotic treatment after 3-6 months can be done. Given the difficulty in their management, we performed a review of AGIs, in order to raise awareness on clinical presentation, current available diagnostic tools, prophylaxis, surgical and anti-infective treatment of AGIs.

Efficacy of Antiseptic Solutions in Treatment of Staphylococcus Aureus Infected Surgical Wounds with Patches of Vascular Graft: An Experimental Study in Rats.

Background and objectives: Treatment of a prosthetic vascular graft infection (PVGI) remains a challenging problem in vascular surgery. The aim of this study was to design a novel rat model for treatment of peripheral vascular prosthesis infection caused by Staphylococcus aureus (S. aureus) and to determine the efficacy of different antiseptic solutions in suppressing or eradicating infection from the wound and the graft material itself. Materials and methods: A piece of Dacron vascular prosthesis was surgically implanted at the dorsum of 48 Wistar rats and the wounds were infected with 5 McFarland standard inoculum of S. aureus. Suppurating wounds were daily irrigated with different antiseptic solutions: octenidine dihydrochloride, povidone-iodine, chlorhexidine digluconate, and sterile saline. The antimicrobial action of antiseptics was defined according to their capability to eradicate bacteria from the graft surroundings and bacteriological examination of the graft itself. Extended studies on wound microbiology, cytology, and histopathology were performed with an additional group of 10 rats, treated with the most effective antiseptic-octenidine dihydrochloride. Results: Four-day treatment course with octenidine, povidone-iodine, and chlorhexidine resulted in 99.98% (p = 0.0005), 90.73% (p = 0.002), and 65.97% (p = 0.004) decrease in S. aureus colonies in wound washouts, respectively. The number of S. aureus colonies increased insignificantly by 19.72% (p = 0.765) in control group. Seven-day treatment course with octenidine eradicated viable bacteria from nine out of 10 wound washouts and sterilized one vascular graft. Conclusions: A reproducible rat model of PVGI with a thriving S. aureus infection was designed. It is a first PVGI animal model where different antiseptic solutions were applied as daily irrigations to treat peripheral PVGI. Seven-day treatment with octenidine eradicated bacteria from the wound washouts for 90% of rats and one vascular graft. Further studies are needed to investigate if irrigations with octenidine could properly cure vascular bed from infection to assure a successful implantation of a new synthetic vascular substitute.

Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections.

BACKGROUND: To evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT), contrast-enhanced CT (CE-CT), and a combined imaging approach (CE-PET/CT) in patients with suspected vascular graft infection (VGI). METHODS: PET/CT and CE-CT were performed prospectively in 23 patients with suspected VGI. Diagnostic accuracy for PET/CT was assessed by using previously suggested cut-off points for maximum standardized uptake values (SUVmax) measured in the vicinity of the graft. Using a new 4-point scale for visual grading, two readers independently assessed the diagnostic accuracy for CE-CT and combined CE-PET/CT. Microbiological culture, obtained after open biopsy or graft explantation, and clinical follow-up of the patients served as the standard of reference. RESULTS: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of PET/CT for the diagnosis of VGI was 100%, 50%, 100%, 72.2%, and 78.3%, using the most favorable SUVmax cut-off ≥ 4.9. Respective values for CE-CT were 100%, 50%, 100%, 72.2%, and 78.3% for reader 1, and 92.3%, 80%, 88.9%, 85.7%, and 86.9% for reader 2; while respective values for combined CE-PET/CT were 100%, 70%, 100%, 81.3%, and 86.9% for reader 1, and 100%, 80%, 100%, 86.7%, and 91.3% for reader 2. Additionally, imaging provided a conclusive clinical diagnosis in patients without graft infection (i.e., other sites of infection): five of ten patients with CE-CT, six of ten patients with PET/CT, and seven of ten patients with combined CE-PET/CT. CONCLUSION: The diagnostic accuracy of combined CE-PET/CT in patients with suspected VGI is very high. The combination of the high sensitivity of PET/CT in detecting metabolically active foci in infection, and the high specificity of CE-CT in detecting anatomic alterations, appears to be the reason why combined imaging outperforms stand-alone imaging in diagnosing VGI and may be supportive in future decision-making of difficult cases of suspected VGI. Clinical Trials.gov Identifier: NCT01821664.

A 57-Year-Old Man With Subacute Progressive Hemoptysis and Fevers.

CASE PRESENTATION: A 57-year-old man was admitted for 1 month of accelerating hemoptysis and hematemesis. Two weeks earlier, he first presented with fevers and hemoptysis of 2 weeks' duration and was diagnosed with community-acquired pneumonia treated with 5 days of ceftriaxone and azithromycin. He improved and was discharged, but his hemoptysis recurred 1 day after discharge and progressed over 9 days, leading to the present admission. He endorsed an 5-kg weight loss, daily fevers up to 39.4°C, and night sweats since discharge. His medical history was significant for peptic ulcer disease complicated by a perforated gastric ulcer 30 years ago, type 2 diabetes, and Barrett esophagus with recent normal upper endoscopy. The patient had coarctation of the aorta repaired 35 years ago. The patient takes aspirin, atorvastatin, and pantoprazole. He emigrated from Mexico 10 years before presentation and lives in Texas with his family. He returns to Mexico several times per year, most recently 2 days before admission. He works at a supermarket. He does not smoke, drink, or use illicit drugs. He denied sick contacts, pets, or incarceration.

Live intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure: observations in an in vivo mouse model of prosthetic vascular material infections.

Objectives: To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs). Methods: We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI. Results: In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells. Conclusions: This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.