Aortic graft infection and mycotic (infected) aortic aneurysms

Anders Wanhainen, MD, PhD¹, Hamid Gavali, MD¹, Ivika Heinola, MD, PhD²

 

 1) Dept. of Surgical Sciences, Vascular Surgery, Uppsala University and Uppsala University Hospital, Uppsala, Sweden

 

2) Department of Vascular Surgery University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

 

 Corresponding author: Anders Wanhainen, Professor of Vascular Surgery, Dept. of Surgical Sciences, Uppsala University, Uppsala, Sweden.

anders.wanhainen@surgsci.uu.se

Aortic Infection is one of the most serious and complex conditions in the field of vascular surgery; it is extremely challenging to handle and comes with high mortality and morbidity. This chapter deal with primary infected aortic aneurysms, so-called mycotic aortic aneurysms (MAA), and aortic graft infections (AGI), including both infection of surgical grafts as well as of stent grafts. The management and challenges of both of these entities have many similarities including the fact that the evidence base is limited and consists mainly of retrospective single centre experiences. Due to the rarity and complexity, it is strongly recommended that MAA and AGI be treated at highly specialized, high-volume centres with a multidisciplinary approach, including dedicated infectious disease specialist.

Definition

The term mycotic aneurysm was coined by Osler in 1885, describing the phenomenon of infectious aneurysms developing secondary to infectious endocarditis¹Osler W. The Gulstonian lectures on malignant endocarditis. Br Med J. 1885;1:467. . The term was originally used to describe the fungal-like vegetation in endocarditis associated with infected aneurysms. From a current aetiological point of view, the name is somewhat misleading as a fungal aneurysm is extremely uncommon. Today the term mycotic aneurysm is defined as all primary and secondary infectious vascular aneurysms, where bacteria are the most common causative pathogens²Sommerville RL, Allen EV, Edwards JE. Bland and infected arteriosclerotic abdominal aortic aneurysms: a clinicopathologic study. Medicine. 1959;38(3):207-22. Involvement of the aorta, i.e. mycotic aortic aneurysms (MAA), is the most frequent site.

 

 

The common pathophysiological aspect of MAAs is that of an established infection in the arterial wall. This causes degradation of the extracellular matrix, and necrosis of the smooth muscle cells in the lamina media due to a combination of the pathogen’s focal invasion and reproduction in the adjacent tissue, production of exotoxins, and the host’s inflammatory response ³Sommerville RL, Allen EV, Edwards JE. Bland and infected arteriosclerotic abdominal aortic aneurysms: a clinicopathologic study. Medicine. 1959;38(3):207-22. This weakening of the arterial wall causes the development of an infected aneurysm. The establishment of the infection in the first place does however vary, partly depending on mechanical reasons and causative pathogens⁴Majeed H, and Ahmad F. Mycotic aneurysm. [Internet]. StatPearls Publishing, 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560736, ⁵Soravia-Dunand VA, Loo VG, Salit IE. Aortitis due to Salmonella: report of 10 cases and comprehensive review of the literature. Clin Infec Dis. 1999;29(4):862-868. :

 

1)     Adherence to a focal atheromatous lesion, or an already established aortic aneurysm secondary to a bacteraemic event/ blood stream infection.

2)     Septic microembolisation to the vasa vasorum of the vessel wall. This mechanism was thought to be more common in the tertiary stages of Treponema Pallidum (Syphilis) as well as in patients with infectious endocarditis or intravenous drug abuse.

3)     Direct vessel wall injury and inoculation of pathogens, for example iatrogenic, at the time of endovascular procedures.

4)     Focal adjacent “invasive infections” that spread to the outer aortic vessel wall. This can occur in patients with psoas abscess, infectious spondylitis or in the rare occurrence of a primary aorto-enteric fistula.

 

Left untreated, beyond the septic complications, the natural outcome of an MAA is that of a rapid expansion, rupture, and death.

 

Incidence

The incidence of MAA depends on the prevalence of risk factors, such as frequency of intravenous drug abuse and immunosuppression in the population, as well as the regional bacteriology. In the western world, approximately 0.5-1.5% of all surgically treated aortic aneurysms are MAAs with older autopsy series citing an incidence closer to 5%, which is likely due to a shift in microbiology⁶Chan FY, Crawford ES, Coselli JS, Safi HJ, Williams Jr TW. In situ prosthetic graft replacement for mycotic aneurysm of the aorta. Ann Thorac Surg. 1989;47:193-203. ,⁷Reddy DJ, Shepard AD, Evans JR, Wright DJ, Smith RF, Ernst CB. Management of Infected Aortoiliac Aneurysms. Arch Surg. 1991;126(7):873–879. ,⁸Parkhurst, GF, and Decker JP. Bacterial aortitis and mycotic aneurysm of the aorta: a report of twelve cases. Am J Pathol. 1995;31(5):821.. In eastern Asia, the microbiology in MAAs is dramatically different due to ecological factors. The incidence of MAA in East Asia is reportedly as high as 5-10% of all surgically treated aortic aneurysms,[ref]Luo CY, Ko WC, Kan CD, Lin PY, Yang Y J. In situ reconstruction of septic aortic pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up. J Vasc Surg. 2003;38(5):975-982.

 

Microbiology

The landscape of microbiological species associated with MAA is best described by dividing MAAs occurring in the West (North America and Europe) vs East Asia (Table 1).

 

 

In the West, Staphylococci species, including both Staphylococcus aureus and Coagulase-negative Staphylococci (CoNS), are the most common bacteria accounting for around 30-40% of MAAs. Depending on reporting, the Gram-positive Streptococci species including Enterococci and the Gram-negative Enterobacteriaceae species (i.e. Escherichia coli) excluding Salmonella species, account for roughly 10-20% of MMAs each⁹Vallejo N, Picardo NE, Bourke P, Bicknell C, Cheshire NJ, Jenkins M P, et al. The changing management of primary mycotic aortic aneurysms. J Vasc Surg. 2011;54(2):334-340. ,¹⁰Laohapensang K, Aworn S, Orrapin S, Rutherford RB. Management of the infected aortoiliac aneurysms. Ann Vasc Dis. 2012;oa-12. ,¹¹Sörelius K, Mani K, Björck M, Sedivy P, Wahlgren CM, Taylor P, et al.. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation. 2014;130(24):2136-2142. , ¹²Sörelius K, Wanhainen A, Wahlgren CM, Langenskiöld M, Roos H, Resch T, et al. Nationwide study on treatment of mycotic thoracic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;57(2):239-246. .

 

In East Asia, however, Salmonella species are the dominant causative microbes, reported in up to 60-70% of MAAs.

In both regions, the culture-negative rate is reported in the range of 20-30%¹³Luo CY, Ko WC, Kan CD, Lin PY, Yang Y J. In situ reconstruction of septic aortic pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up. J Vasc Surg. 2003;38(5):975-982. ,¹⁴Woon CY, Sebastian MG, Tay KH, Tan SG. Extra-anatomic revascularization and aortic exclusion for mycotic aneurysms of the infrarenal aorta and iliac arteries in an Asian population. Am J Surg. 2008;195(1):66-72. .

 

Anatomy

The most common location of an MAA is in the abdominal aorta, which accounts for about 75% of cases; the infrarenal aorta is affected roughly 80% of the time. Infection of the thoracic aorta alone is less common and is reported in the range of 20%; most cases involve the descending aorta. Due to the mechanisms of the infectious dissemination, numerous MAAs can form in the same individual and about 5-10% of patients present with MAAs involving multiple different segments of the aorta¹⁵Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. .

 

Risk factors

Because of the pathogenesis of the disease, i.e. bacterial adhesion to atherosclerotic lesions of the aorta, risk factors associated with atherosclerotic disease are associated with MAAs – including old age, smoking, hypertension, diabetes, presence of non-infected aortic aneurysms and previous cardiovascular disease¹⁶Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. ,¹⁷Miller DV, Oderich GS, Aubry MC, Panneton JM, Edwards WD. Surgical pathology of infected aneurysms of the descending thoracic and abdominal aorta: clinicopathologic correlations in 29 cases (1976 to 1999). Hum. 2004;35(9):1112-1120. ,¹⁸Revest M, Decaux O, Cazalets C, Verohye JP, Jégo P, Grosbois B. Thoracic infectious aortitis: microbiology, pathophysiology and treatment. REV MED INTERNE. 2006;28(2):108-115. .

 

Any process that increases the risk of bacterial translocation or bacteraemic dissemination to the aortic wall is thought to increase the risk of the development of an MAA ¹⁹Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. . This includes: ongoing, respiratory, intraabdominal or urogenital infections, intravenous drug use, concurrent infectious endocarditis, or local infections adjacent to the aorta.

 

Additionally, immunocompromised states are commonly cited as likely to increase the risk of MAA, including chronic corticosteroid use, malignancies, chemotherapy, and the plethora of immunosuppressive agents used in the field of rheumatology ²⁰Oltean M, Herlenius G, Gäbel M, Friman V, Olausson M. Infectious complications after multivisceral transplantation in adults. Transplant. 2006;38:2683-2685.

 

 

Symptoms

Symptoms at presentation reported in patients with MAA are non-specific and associated with the host’s inflammatory response, compression of adjacent tissue and organs or haemodynamic changes due to septic shock, rupture or development of a secondary aortic fistulae to the airways or gastro-intestinal tract.

In a systematic review comprising of 963 patients with an MAA, the most common symptoms were fever (67%) and back- or abdominal pain (77%). A total of 44% presented with rupture and 15% with septic or haemorrhagic shock at the time of diagnosis. Additionally, inflammatory markers such as C-reactive protein (CRP) and total white blood-cell count (WBC) are usually significantly elevated at presentation²¹Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. .

 

Diagnosis

There is currently no consensus or standardisation of the clinical definition and diagnosis of an MAA. The microbiological diagnosis from a positive culture from peri-operative aneurysm wall tissue alone is not always possible due to the negative culture rates, partly explained by administration of antibiotics before to surgical repair.

A suggested clinically pragmatic approach is to define MAA based on the combination of the following three criteria; (1) clinical presentation and perioperative findings such as periaortic infection and fever; (2) laboratory tests showing ongoing infection, and; (3) radiological findings, primarily with computed tomography, and if necessary supporting information from molecular imaging with e.g. positron emission tomography (PET) (Table 2).

 

Definition and classification

Aortic graft infection (AGI) refers to microbial colonisation of prosthetic grafts after aortic reconstruction. Bacterial inoculation occurs via perioperative contamination, haematogenous seeding or by development of direct communication between prosthesis and non-sterile environment e.g. aorto-enteric fistula or exposed graft in open wounds.

 

The Management of Aortic Graft Infection group (MAGIC) has developed a list of minor and major criteria to define AGI, based on the combination of clinical, surgical, radiological and laboratory findings (Figure 2)¹Lyons OT, Baguneid M, Barwick TD, Bell RE, Foster N, Homer-Vanniasinkam S, et al. Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC). Eur J Vasc Endovasc Surg. 2016;52(6):758-763. One major criterion or two minor criteria from different categories are regarded as a suspected AGI. One major criterion and any other criterion from another category defines the definitive AGI diagnosis. If low-virulent skin commensals (e.g. CoNS) are cultured, the same bacteria must be confirmed in another intraoperative specimen and/or blood cultures to exclude contamination. The MAGIC criteria seem reliable in case of a true infection, however, in the case of a possible AGI, slightly reduced specificity may lead to overestimation of suspected cases²Anagnostopoulos A, Mayer F, Ledergerber B, Bergadà-Pijuan J, Husmann L, Mestres CA, et al; VASGRA Cohort Study. 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. Eur J Vasc Endovasc Surg. 2021;62(2):251-257.

 

 

 

The modified Bunt’s classification (Table 3) is used to report the extent of AGI and presence of complications, since management and prognosis are somewhat different ³Bunt TJ. Synthetic vascular graft infections. II. Graft-enteric erosions and graft-enteric fistulas. Surgery. 1983;94(1):1-9.

 

 

The division into early (< 4 month) and late (>4 month) AGI is based on the normal disappearance of fluid around prosthetic graft to distinguish postoperative changes from infection. Early infections are more aggressive featuring virulent bacteria such as Staphylococcus aureus or Gram-negative species. Early AGI is often hospital-acquired, and caused by perioperative contamination or haematogenous dissemination. Late infections are predominantly caused by low-virulent bacteria e.g. Streptococcus epidermidis, which are capable remaining indolent in biofilm for years, only presenting with vague symptoms⁴Bandyk DF, Bergamini TM, Kinney EV, Seabrook GR, Towne JB. In situ replacement of vascular prostheses infected by bacterial biofilms. J Vasc Surg. 1991;13(5):575-83. If a late AGI presents with gram-negative bacteraemia, aorto-enteric connection should be suspected⁵Inui T, Bandyk DF. Vascular surgical site infection: risk factors and preventive measures. Semin Vasc Surg. 2015;28(3-4):201-7.

 

Incidence

The incidence of infection following aortic repair depends on the treatment method, indication and anastomotic sites. In case of open surgical repair (OSR), the reported infection rate is 0.3%–2% and rises to 3% with distal anastomoses in the groin ⁶Swain TW, Calligaro KD, Dougherty MD. Management of Infected Aortic Prosthetic Grafts. Vasc Endovascular Surg. 2004;38:75-82. ,⁷Vogel TR, Symons R, Flum DR. The incidence and factors associated with graft infection after aortic aneurysm repair. J Vasc Surg. 2008;47:264-9, ⁸Berger P, Vaartjes I, Moll FL, De Borst GJ, Blankensteijn JD, Bots ML. Cumulative incidence of graft infection after primary prosthetic aortic reconstruction in the endovascular era. Eur J Vasc Endovasc Surg. 2015;49:581-5. In case of EVAR, the reported incidence remains even lower: 0.2%–1.4% ⁹Antonios VS, Noel AA, Steckelberg JM, Wilson WR, Mandrekar JN, Harmsen WS, et al. Prosthetic vascular graft infection: a risk factor analysis using a case-control study. J Infect. 2006;53:49-55,¹⁰Hobbs SD, Kumar S, Gilling-Smith GL. Epidemiology and diagnosis of endograft infection. J Cardiovasc Surg (Torino). 2010;51:5-14. , ¹¹Cernohorsky P, Reijnen MM, Tielliu IF, van Sterkenburg SM, van den Dungen JJ, Zeebregts CJ. The relevance of aortic endograft prosthetic infection. J Vasc Surg. 2011;54:327-33,¹²Fatima J, Duncan AA, de Grandis E, Oderich GS, Kalra M, Gloviczki P, et al. Treatment strategies and outcomes in patients with infected aortic endografts. J Vasc Surg. 2013;58:371-9,¹³Argyriou C, Georgiadis GS, Lazarides MK, Georgakarakos E, Antoniou GA. Endograft Infection After Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis. J Endovasc Ther. 2017;24:688-697,¹⁴Chaufour X, Gaudric J, Goueffic Y, Khodja RH, Feugier P, Malikov S, et al; AURC (French University Surgeons Association) collaborators. A multicenter experience with infected abdominal aortic endograft explantation. J Vasc Surg. 2017;65:372-380,¹⁵Pettersson J, Daryapeyma A, Gillgren P, Hultgren R. Aortic Graft Infections after Emergency and Non-Emergency Reconstruction: Incidence, Treatment, and Long-Term Outcome. Surg Infect (Larchmt). 2017;18:303-310. One third of infrarenal AGIs are complicated with aorto-enteric erosion or fistula after infrarenal aortic repair despite open or endovascular approach.¹⁶Fatima J, Duncan AA, de Grandis E, Oderich GS, Kalra M, Gloviczki P, et al. Treatment strategies and outcomes in patients with infected aortic endografts. J Vasc Surg. 2013;58:371-9,¹⁷Reilly LM, Altman H, Lusby RJ, Kersh RA, Ehrenfeld WK, Stoney RJ. Late results following surgical management of vascular graft infection. J Vasc Surg. 1984;1:36-44,¹⁸Kahlberg A, Rinaldi E, Piffaretti G, Speziale F, Trimarchi S, Bonardelli S, et al; MAEFISTO collaborators. Results from the Multicenter Study on Aortoenteric Fistulization After Stent Grafting of the Abdominal Aorta (MAEFISTO). J Vasc Surg. 2016;64:313-320, ¹⁹Lejay A, Monnot A, Georg Y, Colvard B, Thaveau F, Geny B, et al. Pathology of graft and stent-graft infections: Lessons learned from examination of explant materials. Semin Vasc Surg. 2017;30:70-74
In the thoracic location, the incidence of aorto-oesophageal or aortobronchial fistulas is 0.5%-1.7% ²⁰Chiesa R, Melissano G, Marone EM, Marrocco-Trischitta MM, Kahlberg A. Aorto-oesophageal and aortobronchial fistulae following thoracic endovascular aortic repair: a national survey. Eur J Vasc Endovasc Surg. 2010;39(3):273-9, ²¹Czerny M, Reser D, Eggebrecht H, Janata K, Sodeck G, Etz C, et al. Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications. Eur J Cardiothorac Surg. 2015;48(2):252-7.

 

 

Pathogenesis

As a foreign body, an aortic prosthetic graft is more susceptible to infection than autologous tissue. Alloplastic implant is a suitable microenvironment for bacterial adhesion and small inoculum is enough to seed the implant ²²Elek SD, Conen PE. The virulence of Staphylococcus pyogenes for man; a study of the problems of wound infection. Br J Exp Pathol. 1957;38:573-86. Blood and tissue proteins facilitate the adhesion by providing adhesion matrix molecules on the surface of the vascular graft ²³Frei E, Hodgkiss-Harlow K, Rossi PJ, Edmiston CE Jr, Bandyk DF. Microbial pathogenesis of bacterial biofilms: a causative factor of vascular surgical site infection. Vasc Endovascular Surg. 2011;45:688-96. Anchored bacteria start secreting extracellular polymers and recruit other pathogens creating a “biofilm”. Formed biofilm offers protection to viable microorganisms against the host defence system, both due to the physical barrier and to the changes in metabolic activity in the pathogens antimicrobial treatment.²⁴Hall MR, McGillicuddy E, Kaplan LJ. Biofilm: basic principles, pathophysiology, and implications for clinicians. Surg Infect (Larchmt). 2014;15:1-7,²⁵Schmitt DD, Bandyk DF, Pequet AJ, Towne JB. Bacterial adherence to vascular prostheses. A determinant of graft infectivity. J Vasc Surg. 1986;3:732-40,²⁶Woźniak W, Bajno R, Świder M, Ciostek P. The Usefulness of Biosynthetic Vascular Graft Omniflow II and Autologous Veins for the Treatment of Massive Infection of Dacron Vascular Graft with Enterococcus faecalis HLAR. Pol J Microbiol. 2017;65(4):471-474
On the graft surface, spreading of biofilm is slow and damage to graft material minimal, but close to the area of graft-to-artery anastomosis, the tensile strength of artery can be reduced and a pseudoaneurysm may form²⁷Frei E, Hodgkiss-Harlow K, Rossi PJ, Edmiston CE Jr, Bandyk DF. Microbial pathogenesis of bacterial biofilms: a causative factor of vascular surgical site infection. Vasc Endovascular Surg. 2011;45:688-96.

 

Bacterial invasion, biofilm formation and planktonic release are irritating to the host causing an immune response. Biofilm-adjacent bacteria are recalcitrant to antibody reaction and phagocytosis, but the chronically stimulated immune response attenuates vascular prosthesis incorporation to surrounding tissue and causes autolysis of perigraft tissue²⁸Frei E, Hodgkiss-Harlow K, Rossi PJ, Edmiston CE Jr, Bandyk DF. Microbial pathogenesis of bacterial biofilms: a causative factor of vascular surgical site infection. Vasc Endovascular Surg. 2011;45:688-96,²⁹Hall MR, McGillicuddy E, Kaplan LJ. Biofilm: basic principles, pathophysiology, and implications for clinicians. Surg Infect (Larchmt). 2014;15:1-7,³⁰White RA & Hollier LH (eds.). Vascular Surgery: Basic Sience and Clinical Correlations, 2-nd Edition. John Wiley & Sons, 2008. Disturbance of encapsulation by fibrous collagen tissue, angiogenesis, and capillary ingrowth, subsequently attenuate the luminal endothelialisation. Lack of luminal endothelia makes the graft more thrombogenic, which increases the attachment sites for haematogenous bacteria.³¹Moore WS, Malone JM, Keown K. Prosthetic arterial graft material. Influence on neointimal healing and bacteremic infectibility. Arch Surg. 1980;115:1379-83, ³²Berger K, Sauvage LR, Rao AM, Wood SJ. Healing of arterial prostheses in man: its incompleteness. Ann Surg. 1972;175:118-27, ³³Reduced susceptibility of polytetrafluoroethylene vascular prostheses to colonization by Staphylococcus aureus following in situ endothelialization. Artif Organs. 1994;18:448-53,³⁴Lejay A, Delay C, Girsowicz E, Chenesseau B, Bonnin E, Ghariani MZ, et al. Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection. Eur J Vasc Endovasc Surg. 2017;54:636-644
In case of vascular prosthetic infection, the presence of a biofilm challenges the conservative treatment and, therefore, graft explant is required for eradication ³⁵Frei E, Hodgkiss-Harlow K, Rossi PJ, Edmiston CE Jr, Bandyk DF. Microbial pathogenesis of bacterial biofilms: a causative factor of vascular surgical site infection. Vasc Endovascular Surg. 2011;45:688-96.

 

Bacteria or fungi can seed vascular graft in four different ways; 1) perioperative contamination; 2) haematogenous seeding by bacteraemia; 3) mechanical erosion of the skin, bronchi or gastrointestinal tract, or; 4) involvement in adjacent infectious process.

 

1) Contamination. Endogenous pathogens from patients’ skin are the most frequent sources of infection. Staphylococci can contaminate the graft through the direct skin contact or after reckless graft handling. Bacteria can also harbour in deeper dermal layers, scar tissue, and sweat glands, remaining relatively unaffected by topical bactericidal agents³⁶Hicks RC, Greenhalgh RM. The pathogenesis of vascular graft infection. Eur J Vasc Endovasc Surg. 1997;14 Suppl A:5-9. Recent previous percutaneous arterial access or surgery may elevate the risk of graft contamination due to introduction of skin flora into subcutaneous tissue and local haematoma. Any redo operation carries a risk of bacterial contamination, including procedures for treating the endoleaks after EVAR³⁷Hobbs SD, Kumar S, Gilling-Smith GL. Epidemiology and diagnosis of endograft infection. J Cardiovasc Surg (Torino). 2010;51:5-14. . Further sources of contamination are accidental opening of genitourinary or gastrointestinal tract, aseptic breakdown in surgical technique (emergent operations), extended operation time and operating in infectious conditions such as mycotic aneurysms³⁸Sörelius K, Mani K, Björck M, Sedivy P, Wahlgren CM, Taylor P, et al.. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation. 2014;130(24):2136-2142. ,³⁹Cronenwett JL & Johnston KW (eds). Rutherford’s Vascular Surgery, 7-th Edition: Saunders, 2010,⁴⁰Capoccia L, Speziale F, Menna D, Esposito A, Sirignano P, Rizzo AR, et al. Collaborators; Preliminary Results from a National Enquiry of Infection in Abdominal Aortic Endovascular Repair (Registry of Infection in EVAR–R.I.EVAR). Ann Vasc Surg. 2016;30:198-204,⁴¹Cheng H, Chen BP, Soleas IM, Ferko NC, Cameron CG, Hinoul P. Prolonged Operative Duration Increases Risk of Surgical Site Infections: A Systematic Review. Surg Infect (Larchmt). 2017;18:722-735.

 

2) Bacteremia. Haematogenous seeding occurs from remote infection sites such as infected urinary tract or during pneumonia. ⁴²Cronenwett JL & Johnston KW (eds). Rutherford’s Vascular Surgery, 7-th Edition: Saunders, 2010 Parenteral antibiotic prophylaxis has diminished the perioperative graft colonisation, but exposed foreign material remains attractive to bacteria in early postoperative period. Possibly incomplete luminal endothelisation leaves the prosthesis vulnerable to any future episodes with virulent bacteraemia, therefore life-long antimicrobial prophylaxis should be considered to patients with aortic prosthetic reconstructions in case of invasive procedures with transient bacteraemia⁴³Moore WS, Malone JM, Keown K. Prosthetic arterial graft material. Influence on neointimal healing and bacteremic infectibility. Arch Surg. 1980;115:1379-83,⁴⁴Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms. Eur J Vasc Endovasc Surg. 2019;57(1):8-93,⁴⁵Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384.

 

3) Mechanical erosion. An aortio-enteric or graft-enteric fistula (AEF/GEF) and aorto-enteric or graft-enteric erosion (AEE/GEE) are a communication between aorta or aortic prosthetic graft and adjacent intestine. Most commonly third part of duodenum becomes involved due to its relatively fixed position and proximity to aortic graft body, when constant pulsatile movements of noncompliant graft cause mechanical microtrauma to duodenum (figure 3). A fistula is usually a result of low-grade infection and anastomotic pseudoaneurysms abrasion, slowly creating a communication between aorta and intestine. In case of erosion, aorto-oesophageal (AOF) or bronchial fistula (ABF), mechanical trauma to intestine, oesophagus or bronchus is the cause and graft contamination with bacteria the result. Hematoma in tight mediastinum or retroperitoneum may aggravate the tissue ischemia and inflammation adding to fistulas formation⁴⁶Bunt TJ. Synthetic vascular graft infections. II. Graft-enteric erosions and graft-enteric fistulas. Surgery. 1983;94(1):1-9,⁴⁷Czerny M, Reser D, Eggebrecht H, Janata K, Sodeck G, Etz C, et al. Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications. Eur J Cardiothorac Surg. 2015;48(2):252-7,⁴⁸Cronenwett JL & Johnston KW (eds). Rutherford’s Vascular Surgery, 7-th Edition: Saunders, 2010. Fistula development after EVAR or TEVAR is often associated with an aortic configuration change due to stiff stentgraft, persistent endoleak and aneurysm growth or endotension⁴⁹Czerny M, Reser D, Eggebrecht H, Janata K, Sodeck G, Etz C, et al. Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications. Eur J Cardiothorac Surg. 2015;48(2):252-7,⁵⁰Spanos K, Kouvelos G, Karathanos C, Matsagkas M, Giannoukas AD. Current status of endovascular treatment of aortoenteric fistula. Semin Vasc Surg. 2017;30:80-84. A non-septic graft-cutaneous fistula is usually associated to low-grade streptococcal infection, causing chronic inflammation and tissue autolysis⁵¹Bergamini TM, Corpus RA Jr, Brittian KR, Peyton JC, Cheadle WG. The natural history of bacterial biofilm graft infection. J Surg Res. 1994;56:393-6.

 

4) Extension of contiguous infection focus. Wound healing complications are a risk factor for an AGI. Presence of wound haematoma or fatty necrosis facilitates the extension of superficial infection to subcutaneous tissue and graft⁵²Inui T, Bandyk DF. Vascular surgical site infection: risk factors and preventive measures. Semin vasc Surg 2015;28:201-7. Colonisation in retroperitoneal space due to diverticulitis, periappendicular abscess or discitis has been described⁵³Perera GB, Fujitani RM, Kubaska SM. Aortic graft infection: update on management and treatment options. Vasc Endovascular Surg. 2006;40:1-10,⁵⁴Laser A, Baker N, Rectenwald J, Eliason JL, Criado-Pallares E, Upchurch GR Jr. Graft infection after endovascular abdominal aortic aneurysm repair. J Vasc Surg. 2011 Jul;54(1):58-63.

 

Microbiology

The specific microbiological etiology in AGI varies depending on the location of the aortic prosthesis, type of primary conduit in the population as well as the frequency of secondary aorto-enteric- and bronchial fistulae. In general, infected aortobifemoral grafts and thoracic grafts are associated with a higher frequency of Gram-positive infections including Staphylococcus aureus and Coagulase negative Staphylococci (CoNS) infections⁵⁵Bianco V, Kilic A, Gleason TG, Arnaoutakis GJ, Sultan I. Management of thoracic aortic graft infections. J Card Surg. 2018;33(10):658-665. . Some 20-30% of AGIs are reported as culture-negative in the literature, likely due to pre-operative antibiotic exposure⁵⁶Smeds MR, Duncan AA, Harlander-Locke MP, Lawrence PF, Lyden S, Fatima J, et al. Treatment and outcomes of aortic endograft infection. J Vasc Surg. 2016;63(2):332-340. ,⁵⁷Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. . In contrast patients with AEF/GEF show a higher frequency of Gram-negative- as well as polymicrobial infections.⁵⁸Smeds et al. J Vasc Surg 2016 and Gavali et al. Eur J Vasc Endovasc Surg 2021 Some 20-30% of AGIs are reported as culture-negative in the literature, likely due to pre-operative antibiotic exposure⁵⁹Smeds MR, Duncan AA, Harlander-Locke MP, Lawrence PF, Lyden S, Fatima J, et al. Treatment and outcomes of aortic endograft infection. J Vasc Surg. 2016;63(2):332-340. ,⁶⁰Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. . Recent studies have shown that the frequency of fungal infections in AGI patients with a GEF can be as high as 30%⁶¹Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. ,⁶²Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. . Table 4 shows the reported microbiological etiology identified on blood- and peri-operative cultures in 120 radically surgically treated abdominal AGI patients with and without a GEF ⁶³Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. .

 

 

 

Risk factors

Deprivation of host immune reaction due to diabetes, malnutrition, malignancy, chronic end-stage renal disease, long-term corticosteroid treatment, antirejection on cytostatic medicaments, lymphoproliferative disease or autoimmune disorders raise the susceptibility to AGI ⁶⁴Cronenwett JL & Johnston KW (eds). Rutherford’s Vascular Surgery, 7-th Edition: Saunders, 2010. Obesity is a risk factor for wound infection and subsequently possibly to graft contamination⁶⁵Anderson K, Hamm RL. Factors That Impair Wound Healing. J Am Coll Clin Wound Spec. 2014;4:84-91. Prolonged preoperative hospital stay, and nasal carriage of Methicillin-resistant Staphylococcus aureus (MRSA) are yet another risk factor for AGI⁶⁶Inui T, Bandyk DF. Vascular surgical site infection: risk factors and preventive measures. Semin Vasc Surg. 2015;28(3-4):201-7.

 

Prevention

Multifactorial prevention of AGI consists of pre-, peri- and postoperative methods listed in Table 5.

 

Diagnosis

Once vascular graft/endograft infection is suspected, exhaustive evaluation of clinical status, signs of infection and patient comorbidities according to the MAGIC criteria (Figure 2) is recommended⁶⁷Lyons OT, Baguneid M, Barwick TD, Bell RE, Foster N, Homer-Vanniasinkam S, et al. Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC). Eur J Vasc Endovasc Surg. 2016;52(6):758-763,⁶⁸Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384.

 

Clinical presentation

The non-specific nature of AGI symptoms and the intracavitary location require high index of suspicion to perform radiological studies for diagnosis.

 

High-virulent bacteria are more common in early infections, presenting with aggressive symptoms such as fever and abdominal or back pain. Sepsis and fever are present in up to 70% of cases⁶⁹Kieffer E, Gomes D, Chiche L, Fléron MH, Koskas F, Bahnini A. Allograft replacement for infrarenal aortic graft infection: early and late results in 179 patients. J Vasc Surg. 2004;39:1009-17,⁷⁰Daenens K, Fourneau I, Nevelsteen A. Ten-year experience in autogenous reconstruction with the femoral vein in the treatment of aortofemoral prosthetic infection. Eur J Vasc Endovasc Surg. 2003;25:240-5,⁷¹Davila VJ, Stone W, Duncan AA, Wood E, Jordan WD Jr, Zea N, et al. A multicenter experience with the surgical treatment of infected abdominal aortic endografts. J Vasc Surg. 2015;62:877-83. Low-grade infections are typically caused by low-virulent bacteria, appear later and present with vague symptoms – general malaise, weakness, weight loss or anorexia.

 

Groin sinuses, femoral pseudoaneurysms, graft thrombosis, erythema over the graft, and cellulitis are symptoms associated with AGI ⁷²Kieffer E, Gomes D, Chiche L, Fléron MH, Koskas F, Bahnini A. Allograft replacement for infrarenal aortic graft infection: early and late results in 179 patients. J Vasc Surg. 2004;39:1009-17,⁷³Daenens K, Fourneau I, Nevelsteen A. Ten-year experience in autogenous reconstruction with the femoral vein in the treatment of aortofemoral prosthetic infection. Eur J Vasc Endovasc Surg. 2003;25:240-5,⁷⁴Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9. Hematemesis or hemoptysis are signs of AOF and ABF, respectively. Therefore, signs of herald bleeding or sepsis of unknown etiology, and history of aortic reconstruction, should urgently lead to further investigations⁷⁵Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,⁷⁶Bergqvist D, Björck M. Secondary arterioenteric fistulation–a systematic literature analysis. Eur J Vasc Endovasc Surg. 2009;37:31-42, ⁷⁷Batt M, Jean-Baptiste E, O’Connor S, Saint-Lebes B, Feugier P, Patra P, et al. Early and late results of contemporary management of 37 secondary aortoenteric fistulae. Eur J Vasc Endovasc Surg. 2011;41:748-57,⁷⁸Oderich GS, Bower TC, Hofer J, Kalra M, Duncan AA, Wilson JW, et al. In situ rifampin-soaked grafts with omental coverage and antibiotic suppression are durable with low reinfection rates in patients with aortic graft enteric erosion or fistula. J Vasc Surg. 2011;53:99-106

 

Completely intracavitary aortic endograft infections are mostly highly symptomatic and present with sepsis or symptoms associated with fistula formation.⁷⁹Hobbs SD, Kumar S, Gilling-Smith GL. Epidemiology and diagnosis of endograft infection. J Cardiovasc Surg (Torino). 2010;51:5-14. ,⁸⁰Chaufour X, Gaudric J, Goueffic Y, Khodja RH, Feugier P, Malikov S, et al; AURC (French University Surgeons Association) collaborators. A multicenter experience with infected abdominal aortic endograft explantation. J Vasc Surg. 2017;65:372-380,⁸¹Kahlberg A, Grandi A, Loschi D, Vermassen F, Moreels N, Chakfé N, et al. A systematic review of infected descending thoracic aortic grafts and endografts. J Vasc Surg. 2019;69(6):1941-1951.

 

Laboratory findings

Elevated leukocyte count and CRP are common, but not pathognomonic of AGI. CRP is elevated during the postoperative period and therefore not indicative of an infection. In treatment follow-up, inflammatory markers are useful in evaluation of treatment effectiveness ⁸²Wilson WR, Bower TC, Creager MA, Amin-Hanjani S, O’Gara PT, Lockhart PB, et al. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Council on Peripheral Vascular Disease; and Stroke Council. Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association. Circulation. 2016;134:e412-e460. .

 

Microbiological diagnostics are crucial, and great care should be taken in sampling (Table 6). Blood cultures are reported to be positive in about half of AGI patients, and overall positive bacterial cultures is reported in up to 80% of the cases. (See Bacteriology for details) ⁸³Hobbs SD, Kumar S, Gilling-Smith GL. Epidemiology and diagnosis of endograft infection. J Cardiovasc Surg (Torino). 2010;51:5-14. , ⁸⁴Kahlberg A, Rinaldi E, Piffaretti G, Speziale F, Trimarchi S, Bonardelli S, et al; MAEFISTO collaborators. Results from the Multicenter Study on Aortoenteric Fistulization After Stent Grafting of the Abdominal Aorta (MAEFISTO). J Vasc Surg. 2016;64:313-320,⁸⁵Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,⁸⁶Batt M, Jean-Baptiste E, O’Connor S, Saint-Lebes B, Feugier P, Patra P, et al. Early and late results of contemporary management of 37 secondary aortoenteric fistulae. Eur J Vasc Endovasc Surg. 2011;41:748-57,⁸⁷Bisdas T, Bredt M, Pichlmaier M, Aper T, Wilhelmi M, Bisdas S, et al. Eight-year experience with cryopreserved arterial homografts for the in situ reconstruction of abdominal aortic infections. J Vasc Surg. 2010;52:323-30,⁸⁸Garot M, Delannoy PY, Meybeck A, Sarraz-Bournet B, d’Elia P, d’Escrivan T, et al. Intra-abdominal aortic graft infection: prognostic factors associated with in-hospital mortality. BMC Infect Dis. 2014;14:215. Isolated true pathogens from explanted graft or perigraft fluid/tissue have a strong diagnostic value, however skin commensals may sometimes refer to contamination. Perioperative fungal samples are important, since fungi is common for AEF/GEF and AEE/GEE patients and predicts poorer outcome⁸⁹Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. ,⁹⁰Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. ,⁹¹Omran S, Raude B, Bürger M, Kapahnke S, Carstens JC, Haidar H, et al. Aortoduodenal fistulas after endovascular abdominal aortic aneurysm repair and open aortic repair. J Vasc Surg. 2021;74(3):711-719
. 16s-rRNA PCR and bacterial DNA sequencing should be routine, sonication may offer further benefit⁹²Lyons OT, Baguneid M, Barwick TD, Bell RE, Foster N, Homer-Vanniasinkam S, et al. Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC). Eur J Vasc Endovasc Surg. 2016;52(6):758-763,⁹³Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384.

 

Radiological studies

Diagnosis of AGI relies on radiological studies, providing information on the extent and specifics of infection and enabling the planning of the possible surgical reconstruction.

 

Computed tomography angiography (CTA) provides sufficient data on the vascular tree and adjacent structures and is the primary imaging modality for AGI diagnosis (Figure 4). Perigraft fluid, gas, soft-tissue oedema, pseudoaneurysms and focal bowel wall thickening can be easily discerned, however, distinguishing normal postoperative changes from infection is challenging in the early postoperative period. ⁹⁴Fiorani P, Speziale F, Rizzo L, De Santis F, Massimi GJ, Taurino M, et al. Detection of aortic graft infection with leukocytes labeled with technetium 99m-hexametazime. J Vasc Surg. 1993;17:87-95,⁹⁵Orton DF, LeVeen RF, Saigh JA, Culp WC, Fidler JL, Lynch TJ, et al. Aortic prosthetic graft infections: radiologic manifestations and implications for management. Radiographics. 2000;20:977-93
Perigraft fluid persisting over 3 months and perigraft air persisting over 7 weeks are suspicious to an infection (18). AEF/GEF and AEE/GEE is characterized in CTA scan with disappearance of the periaortic fat plane between aorta and bowel, ectopic gas and pseudoaneurysms ⁹⁶Hagspiel KD, Turba UC, Bozlar U, Harthun NL, Cherry KJ, Ahmed H, et al. Diagnosis of aortoenteric fistulas with CT angiography. J Vasc Interv Radiol. 2007;18:497-504. . Additionally, CT can detect other occasionally co-existing conditions, such as more remote abscesses, discitis or hydronephrosis⁹⁷Orton DF, LeVeen RF, Saigh JA, Culp WC, Fidler JL, Lynch TJ, et al. Aortic prosthetic graft infections: radiologic manifestations and implications for management. Radiographics. 2000;20:977-93.

 

Magnetic resonance imaging (MRI) is more sensitive to smaller amounts of liquid and allows for the differentiation between perigraft fluid with inflammatory changes, however, it cannot differentiate between infected and sterile liquid in early postoperative period.

 

Radionuclide Molecular Imaging methods are complimentary if conventional ones yield inconclusive results⁹⁸Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,⁹⁹Shahidi S, Eskil A, Lundof E, Klaerke A, Jensen BS. Detection of abdominal aortic graft infection: comparison of magnetic resonance imaging and indium-labeled white blood cell scanning. Ann Vasc Surg. 2007;21:586-92. 18F – FDG-PET/CT and WBCS combined with single-photon emission CT (SPECT/CT) provide information on aggravated inflammatory cell activity and correlated anatomic locations. Increased metabolic activity in 18F – FDG-PET/CT refers to an inflammatory process, however, focal, or segmental glucose uptake pattern suggests an infection, compared to diffuse pattern in case on inflammation¹⁰⁰Fukuchi K, Ishida Y, Higashi M, Tsunekawa T, Ogino H, Minatoya K, et al. Detection of aortic graft infection by fluorodeoxyglucose positron emission tomography: comparison with computed tomographic findings. J Vasc Surg 2005;42(5):919-25,¹⁰¹Saleem BR, Pol RA, Slart RH, Reijnen MM, Zeebregts CJ. 18F-Fluorodeoxyglucose positron emission tomography/CT scanning in diagnosing vascular prosthetic graft infection. Biomed Res Int. 2014;2014:471971
. Standardised uptake value (SUV) of >8 is the current estimated cut-off value for infected grafts (Figure 5) ¹⁰²Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,¹⁰³Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, et al. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015;61:965-71. WBCS reveals pathological accumulation of radiolabelled white blood cells. It requires several scans for results and is therefore labouring and time consuming. SPECT/CT adds accuracy and yields slightly better results in specificity compared to 18F – FDG-PET/CT.

 

 

The treatment strategy of AGI and MAA should be decided and executed by a multidisciplinary team, including vascular surgeons, gastrointestinal surgeons, infection disease specialists, radiologists, and anaesthesiologist. The tailor-made decision is based on patient-centered factors such as frailty and comorbidities, the severity of the infection as well as causative pathogens, the availability of treatment methods and the hospitals experience ¹Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384.

 

The treatment strategy can aim for; 1) cure by means of radical surgical treatment; 2) infectious control by means of semiconservative treatment with partial resection of the infected graft and often long-term antimicrobial treatment, or 3) palliative treatment, with antimicrobial treatment alone, or sometimes with the addition of endovascular bleeding control. In addition, endografting to control a bleeding can serve as a temporary bridge to later radial surgical treatment.

 

During the past 20 years, MAAs have been treated with EVAR without the resection of the infected aneurysm, and today endovascular repair is considered an acceptable alternative to open repair for MAA ²Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms. Eur J Vasc Endovasc Surg. 2019;57(1):8-93. Recent studies with long-term follow-up suggest that EVAR have a short-term benefit over open surgical repair (OSR), with similar long-term outcome³Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, et al. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015;61:965-71. However, because of the heterogeneity and rarity of MAA strong evidence is lacking, which makes firm recommendations difficult, and an individualized approach is strongly recommended.

 

In situ reconstructions (ISR) for abdominal aortic infections

Surgical debridement of the infected material with subsequent arterial revascularization in combination with antimicrobial therapy are the cornerstones of infection eradication. When feasible, resection of the infected graft or mycotic aneurysm with meticulous debridement and in situ reconstruction yields better patency and fewer amputations than axillobifemoral bypass⁴Batt M, Feugier P, Camou F, Coffy A, Senneville E, Caillon J, et al; Research Group for Vascular Graft Infection. A Meta-Analysis of Outcomes After In Situ Reconstructions for Aortic Graft Infection.Angiology. 2018;695:370-379,⁵O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg. 2006;44:38-45. However, controversy concerning the preferred conduit material exists.

 

1) Prosthetic reconstructions. Prosthetic interposition is accomplished with bare grafts, rifampicin-soaked or silver-coated polyester grafts ⁶Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,⁷Oderich GS, Bower TC, Hofer J, Kalra M, Duncan AA, Wilson JW, et al. In situ rifampin-soaked grafts with omental coverage and antibiotic suppression are durable with low reinfection rates in patients with aortic graft enteric erosion or fistula. J Vasc Surg. 2011;53:99-106,⁸Lin CH, Hsu RB. Primary Infected Aortic Aneurysm: Clinical Presentation, Pathogen, and Outcome. Acta Cardiol Sin. 2014;30:514-21,⁹Batt M, Magne JL, Alric P, Muzj A, Ruotolo C, Ljungstrom KG, et al. In situ revascularization with silver-coated polyester grafts to treat aortic infection: early and midterm results. J Vasc Surg. 2003;38:983-9. Availability, familiarity, low cost, and low amputation-rates support the widespread use, however re-infection rates of up to 21% and linked mortality are concerning ¹⁰Sörelius K, Wanhainen A, Furebring M, Björck M, Gillgren P, Mani K, et al. Nationwide study of the treatment of mycotic abdominal aortic aneurysms comparing open and endovascular repair. Circulation. 2016;134(23):1822-1832. ,¹¹Batt M, Magne JL, Alric P, Muzj A, Ruotolo C, Ljungstrom KG, et al. In situ revascularization with silver-coated polyester grafts to treat aortic infection: early and midterm results. J Vasc Surg. 2003;38:983-9. Careful patient selection, avoidance of virulent bacteria and gross local contamination as well as graft omental wrapping may diminish the reinfection-rates below 10% with rifampicin-soaked or silver grafts¹²Oderich GS, Bower TC, Hofer J, Kalra M, Duncan AA, Wilson JW, et al. In situ rifampin-soaked grafts with omental coverage and antibiotic suppression are durable with low reinfection rates in patients with aortic graft enteric erosion or fistula. J Vasc Surg. 2011;53:99-106,¹³Batt M, Feugier P, Camou F, Coffy A, Senneville E, Caillon J, et al; Research Group for Vascular Graft Infection. A Meta-Analysis of Outcomes After In Situ Reconstructions for Aortic Graft Infection.Angiology. 2018;695:370-379,¹⁴Batt M, Magne JL, Alric P, Muzj A, Ruotolo C, Ljungstrom KG, et al. In situ revascularization with silver-coated polyester grafts to treat aortic infection: early and midterm results. J Vasc Surg. 2003;38:983-9. Rifampicin is protective against staphylococci, however, its concentration dilutes fast and rifampicin-resistant strains may emerge ¹⁵Berard X, Puges M, Pinaquy JB, Cazanave C, Stecken L, Bordenave L, et al. In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan Containing Vascular Grafts Compared with Rifampicin Soaked Grafts. Eur J Vasc Endovasc Surg. 2019;57(3):424-432. Recent in vitro studies with triclosan coated silver acetate grafts suggest better resistance to Staphylococci, Escherichia Coli and Candida species, nevertheless, the clinical evidence is currently lacking¹⁶Berard X, Puges M, Pinaquy JB, Cazanave C, Stecken L, Bordenave L, et al. In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan Containing Vascular Grafts Compared with Rifampicin Soaked Grafts. Eur J Vasc Endovasc Surg. 2019;57(3):424-432. Despite shorter operation time compared to biological grafts, the late mortality remains higher when prosthetic reconstruction material is used¹⁷Smeds MR, Duncan AA, Harlander-Locke MP, Lawrence PF, Lyden S, Fatima J, et al. Treatment and outcomes of aortic endograft infection. J Vasc Surg. 2016;63(2):332-340. .

 

2) Autologous femoral vein grafts. Immunologically excellent autologous femoral veins (FV) are appealing due to suitable diameter, however, history of deep venous thrombosis or advanced chronic limb ischemia deny the harvest. Y-shaped configuration sewn from bilaterally harvested grafts matches the aortic diameter and allows for a tension free upper anastomosis¹⁸Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,¹⁹Clagett GP, Bowers BL, Lopez-Viego MA, Rossi MB, Valentine RJ, Myers SI, et al. Creation of a neo-aortoiliac system from lower extremity deep and superficial veins. Ann Surg. 1993;218:239-48,²⁰Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9. Low re-infection rates around 0-5% and rare graft thrombosis with amputation rates less than 7% are the advantages, but lengthy operation and vast surgical trauma prohibit the treatment from old and frail patients ²¹Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,²²Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,²³Heinola I, Sörelius K, Wyss TR, Eldrup N, Settembre N, Setacci C, et al. Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study. J Am Heart Assoc. 2018;7(12):e008104. Nevertheless, successful infection control results in low postoperative mortality of 9% and late mortality of 40%²⁴Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,²⁵Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,²⁶Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,²⁷Heinola I, Sörelius K, Wyss TR, Eldrup N, Settembre N, Setacci C, et al. Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study. J Am Heart Assoc. 2018;7(12):e008104. Post-harvest swelling is usually mild and treated with support stocking when necessary. Stenotic graft complications are infrequent when using at least 7 mm FVs²⁸Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,²⁹Beck AW, Murphy EH, Hocking JA, Timaran CH, Arko FR, Clagett GP. Aortic reconstruction with femoral-popliteal vein: graft stenosis incidence, risk and reintervention. J Vasc Surg. 2008;47:36-43. FVs are preoperatively scanned with ultrasound to assess the size and quality. Veins are harvested from popliteal fossa to femoral confluence, leaving the deep femoral vein patent for venous drainage³⁰Berard X, Puges M, Pinaquy JB, Cazanave C, Stecken L, Bordenave L, et al. In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan Containing Vascular Grafts Compared with Rifampicin Soaked Grafts. Eur J Vasc Endovasc Surg. 2019;57(3):424-432,³¹Clagett GP, Bowers BL, Lopez-Viego MA, Rossi MB, Valentine RJ, Myers SI, et al. Creation of a neo-aortoiliac system from lower extremity deep and superficial veins. Ann Surg. 1993;218:239-48. Side branches are ligated, the veins are everted and valves excised under direct vision. After re-eversion, grafts are split proximally and sewn together to “pantaloon” configuration with 4-0 polypropylene³²Kieffer E, Gomes D, Chiche L, Fléron MH, Koskas F, Bahnini A. Allograft replacement for infrarenal aortic graft infection: early and late results in 179 patients. J Vasc Surg. 2004;39:1009-17,³³Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,³⁴Heinola I, Kantonen I, Mattila I, Albäck A, Venermo M. Cryopreserved Venous Allografts in Supra-inguinal Reconstructions: A Single Centre Experience. Eur J Vasc Endovasc Surg. 2019;58(6):912-919. After FV harvest, in addition to LMWH therapy, lower limb intermittent pneumatic pumps are recommended to avoid excessive swelling and deep vein thrombosis ³⁵Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9, ³⁶Heinola I, Sörelius K, Wyss TR, Eldrup N, Settembre N, Setacci C, et al. Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study. J Am Heart Assoc. 2018;7(12):e008104 (Figure 6).

 

3) Cryopreserved allografts. Cryopreserved allografts (CAG) are equally infection resistant alternatives to autologous FV grafts. Cryopreservation diminishes the immunogenicity, however, handling while freezing and thawing predisposes allografts to structural changes and therefore may contribute to graft degeneration and acute arterial thrombosis.³⁷Lejay A, Delay C, Girsowicz E, Chenesseau B, Bonnin E, Ghariani MZ, et al. Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection. Eur J Vasc Endovasc Surg. 2017;54:636-644³⁸Heinola I, Kantonen I, Mattila I, Albäck A, Venermo M. Cryopreserved Venous Allografts in Supra-inguinal Reconstructions: A Single Centre Experience. Eur J Vasc Endovasc Surg. 2019;58(6):912-919,³⁹Vogt PR, Brunner-LaRocca HP, Lachat M, Ruef C, Turina MI. Technical details with the use of cryopreserved arterial allografts for aortic infection: influence on early and midterm mortality. J Vasc Surg. 2002 Jan;35:80-6. . Following strict handling protocols the CAG are thawed slowly and cryoprotectant washed out, and side branches are ligated⁴⁰Lejay A, Delay C, Girsowicz E, Chenesseau B, Bonnin E, Ghariani MZ, et al. Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection. Eur J Vasc Endovasc Surg. 2017;54:636-644,⁴¹Heinola I, Kantonen I, Mattila I, Albäck A, Venermo M. Cryopreserved Venous Allografts in Supra-inguinal Reconstructions: A Single Centre Experience. Eur J Vasc Endovasc Surg. 2019;58(6):912-919. Creating tension-free anastomosis results in lesser aneurysmatic degeneration, but rupture rate over 5% and acute thrombosis up to 12% are the drawbacks of arterial CAG⁴²Anagnostopoulos A, Mayer F, Ledergerber B, Bergadà-Pijuan J, Husmann L, Mestres CA, et al; VASGRA Cohort Study. 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. Eur J Vasc Endovasc Surg. 2021;62(2):251-257,⁴³Harlander-Locke MP, Harmon LK, Lawrence PF, Oderich GS, McCready RA, Morasch MD, et al. The use of cryopreserved aortoiliac allograft for aortic reconstruction in the United States. J Vasc Surg. 2014;59:669-74,⁴⁴Minga Lowampa E, Holemans C, Stiennon L, Van Damme H, Defraigne JO. Late Fate of Cryopreserved Arterial Allografts. Eur J Vasc Endovasc Surg. 2016;52(5):696-702. One small study reported no thrombotic complications at 1-year follow-up while using cryopreserved femoral vein allografts instead of arterial ones, however long-term results remain unknown⁴⁵Heinola I, Kantonen I, Mattila I, Albäck A, Venermo M. Cryopreserved Venous Allografts in Supra-inguinal Reconstructions: A Single Centre Experience. Eur J Vasc Endovasc Surg. 2019;58(6):912-919.

 

4) Xenopericardial grafts. Readily available bovine pericardium sheets can be tailored into tube grafts or bifurcated ones using vascular staplers or polypropylene thread (Figure 7)⁴⁶Weiss S, Tobler EL, von Tengg-Kobligk H, Makaloski V, Becker D, Carrel TP, et al. Self Made Xeno-pericardial Aortic Tubes to Treat Native and Aortic Graft Infections. Eur J Vasc Endovasc Surg. 2017;54:646-652. Being inexpensive, biocompatible, and fully biological, they are eagerly adopted for short interpositions and thoracic aortic reconstructions ⁴⁷Weiss S, Tobler EL, von Tengg-Kobligk H, Makaloski V, Becker D, Carrel TP, et al. Self Made Xeno-pericardial Aortic Tubes to Treat Native and Aortic Graft Infections. Eur J Vasc Endovasc Surg. 2017;54:646-652,⁴⁸Czerny M, von Allmen R, Opfermann P, Sodeck G, Dick F, Stellmes A, et al. Self-made pericardial tube graft: a new surgical concept for treatment of graft infections after thoracic and abdominal aortic procedures. Ann Thorac Surg. 2011;92:1657-62. Graft re-intervention rates are less than 10% and reinfection rate 6%, nevertheless, long-term data is missing⁴⁹Hostalrich A, Ozdemir BA, Sfeir J, Solovei L, Alric P, Canaud L. Systematic review of native and graft-related aortic infection outcome managed with orthotopic xenopericardial grafts. J Vasc Surg. 2019;69(2):614-618.

 

Technique. Prior aortic re-do surgery, ureter-stents may be inserted to ease the ureter-identification among inflammatory tissue. The infected artery or graft is exposed, aorta and graft limbs clamped, graft excised, and grossly infected tissue debrided. If AEF/GEF is suspected, the attached intestine is left in place until the aorta is clamped. Thereafter intestine is dissected free and temporary closure with sutures or stapler applied to avoid further spillage. The debrided area is irrigated with copious saline or povidone-iodine, distal tunnels may be additionally flushed with hydrogen peroxide.⁵⁰Lin CH, Hsu RB. Primary Infected Aortic Aneurysm: Clinical Presentation, Pathogen, and Outcome. Acta Cardiol Sin. 2014;30:514-21,⁵¹Batt M, Magne JL, Alric P, Muzj A, Ruotolo C, Ljungstrom KG, et al. In situ revascularization with silver-coated polyester grafts to treat aortic infection: early and midterm results. J Vasc Surg. 2003;38:983-9,⁵²Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,⁵³Vogt PR, Brunner-LaRocca HP, Lachat M, Ruef C, Turina MI. Technical details with the use of cryopreserved arterial allografts for aortic infection: influence on early and midterm mortality. J Vasc Surg. 2002 Jan;35:80-6.
In case on FV or CAG, tension-free proximal anastomosis is recommended to enforce with a piece of tensior fasciae lata; for CVG also lower anastomoses to diminish the possibility for anastomotic aneurysmatic degeneration⁵⁴Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,⁵⁵Heinola I, Kantonen I, Mattila I, Albäck A, Venermo M. Cryopreserved Venous Allografts in Supra-inguinal Reconstructions: A Single Centre Experience. Eur J Vasc Endovasc Surg. 2019;58(6):912-919. Definitive intestinal repair is achieved via resection and enteroanastomosis, or simple suture, if the defect is superficial and small. The aortic reconstruction is covered with vital retroperitoneal tissue or omental plasty, groin-anastomoses with sartorius myoplasty. Pediceled omentum is applied ante- or retrocolically through the lesser sac and anchored to vital retroperitoneal tissue around the aortic reconstruction. Vascularised tissue eliminates the dead space, keeps the graft separated from the bowel and enhances perigraft blood circulation. Drainage is left to the abdominal cavity, proximity to the intestinal repair and bilaterally to the sartorius muscle pockets.

Extra-anatomic reconstructions (EAR) for abdominal aortic infections

Prosthetic axillobifemoral bypass is performed first via uninfected area with anastomoses to the level of proximal femoral artery to avoid infected groins. After wound closure and careful coverage, laparotomy and resection of infected graft and tissue are performed. Aortic stump is over sewn in two layers on uninfected level, suture line is reinforced with fascia or xenopericardium to avoid blow-out and covered with omentum. In case of an endograft infection, infrarenal stump management may be difficult owing to hook-fixation damage and therefore ISR could be a more viable solution. After copious irrigation of the infected field, abdominal cavity drainage is placed. The operation can be performed in two stages with few days apart to avoid further bacterial contamination⁵⁶Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,⁵⁷Seeger JM, Pretus HA, Welborn MB, Ozaki CK, Flynn TC, Huber TS. Long-term outcome after treatment of aortic graft infection with staged extra-anatomic bypass grafting and aortic graft removal. J Vasc Surg. 2000;32(3):451-9.

Despite avoidance of the infected area, the prosthesis is inserted into a poorly perfused subcutaneous fat-plane resulting in reinfection rates up to 27%.⁵⁸Batt M, Jean-Baptiste E, O’Connor S, Saint-Lebes B, Feugier P, Patra P, et al. Early and late results of contemporary management of 37 secondary aortoenteric fistulae. Eur J Vasc Endovasc Surg. 2011;41:748-57,⁵⁹O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg. 2006;44:38-45,⁶⁰Jausseran JM, Stella N, Courbier R, Bergeron P, Ferdani M, Houel H, et al. Total prosthetic graft excision and extra-anatomic bypass. Eur J Vasc Endovasc Surg. 1997 Dec;14 Suppl A:59-65. ,⁶¹Woon CY, Sebastian MG, Tay KH, Tan SG. Extra-anatomic revascularization and aortic exclusion for mycotic aneurysms of the infrarenal aorta and iliac arteries in an Asian population. Am J Surg. 2008;195:66-72. Compared to ISR, EAR carries a higher risk of graft complications, including thrombosis, amputation and aortic stump blowout leading to poor long-term survival. Therefore, EAR is not recommended for fit patients, but remains as a viable option in case of multiresistant virulent bacteria for patients in poor condition or of an advanced age⁶²Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384,⁶³Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. , ⁶⁴Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. ,⁶⁵Wilson WR, Bower TC, Creager MA, Amin-Hanjani S, O’Gara PT, Lockhart PB, et al. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Council on Peripheral Vascular Disease; and Stroke Council. Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association. Circulation. 2016;134:e412-e460. ,⁶⁶O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg. 2006;44:38-45,⁶⁷Batt M, Magne JL, Alric P, Muzj A, Ruotolo C, Ljungstrom KG, et al. In situ revascularization with silver-coated polyester grafts to treat aortic infection: early and midterm results. J Vasc Surg. 2003;38:983-9.

 

Endovascular repair for abdominal aortic infections

EVAR has no role in the definitive treatment of AGI, other than as an urgent temporary measure in case of an AGI with hemorrhagic AEF/GEF, ruptured pseudoaneurysm or anastomosis dehiscence. EVAR is, however, a valid treatment option for MAA, especially for older and comorbid patients who are not candidates for major radical OSR (52). The low postoperative morbidity and mortality of less than 10% should, however, be weighed against the risk of reinfections of over 20%⁶⁸Sörelius K, Mani K, Björck M, Sedivy P, Wahlgren CM, Taylor P, et al.. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation. 2014;130(24):2136-2142. ,⁶⁹Sörelius K, Wanhainen A, Furebring M, Björck M, Gillgren P, Mani K, et al. Nationwide study of the treatment of mycotic abdominal aortic aneurysms comparing open and endovascular repair. Circulation. 2016;134(23):1822-1832. . Antimicrobial treatment at least a week prior surgery, until bacterial cultures become negative, seem to diminish the infection-related complications, and is thereby recommended⁷⁰Sörelius K, Wanhainen A, Wahlgren CM, Langenskiöld M, Roos H, Resch T, et al. Nationwide study on treatment of mycotic thoracic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;57(2):239-246. ,⁷¹Kan CD, Lee HL, Yang YJ. Outcome after endovascular stent graft treatment for mycotic aortic aneurysm: a systematic review. J Vasc Surg. 2007;46:906-12. Nevertheless, the benefit of waiting must be juxtaposed with substantial risk of rupture and therefore, low threshold kept for earlier surgery if clinical condition changes. For a septic and unstable patient, EVAR can also serve as a bridge to definitive surgical treatment in later phase.

 

Surgical treatment of thoracic aortic infections

Thoracic aortic graft explant requires often cardiopulmonary bypass or left heart bypass with hypothermia adding morbidity. Access via median sternotomy or left thoracotomy depends on whether aortic arch is involved, or infected graft is located distal to the left subclavian artery. Extra-anatomical bypass is often not feasible and therefore orthotopic reconstruction is recommended once graft explant is planned. Owing to availability and suitable size, Dacron grafts with or without rifampicin are most commonly used reconstruction material. ⁷²Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384 Biological alternatives are cryopreserved arterial allografts and self-made XPTs. First ones have the advantage of anatomical configuration and sidebranches for innominate artery and carotid, nonetheless, early complications such as pseudoaneurysms and later fistulas are speculated to be associated with ongoing infection and therefore close surveillance is necessary ⁷³Corvera JS, Blitzer D, Copeland H, Murphy D, Hess PJ Jr, Pillai ST, Fehrenbacher JW. Repair of Thoracic and Thoracoabdominal Mycotic Aneurysms and Infected Aortic Grafts Using Allograft. Ann Thorac Surg. 2018;106(4):1129-1135. XPTs can be tailored to perfect fit and by being reinfection resistant have gained popularity despite the lack of long-term results⁷⁴Czerny M, von Allmen R, Opfermann P, Sodeck G, Dick F, Stellmes A, et al. Self-made pericardial tube graft: a new surgical concept for treatment of graft infections after thoracic and abdominal aortic procedures. Ann Thorac Surg. 2011;92:1657-62.

Extra-anatomical bypass, called ventral aorta, is a retrosternally placed graft originating from ascending aorta and with distal anastomosis in suprarenal or infrarenal abdominal aorta. Two stage procedure is feasible, first performing reconstruction through sternotomy and laparotomy, afterwards removing infected graft through thoracotomy⁷⁵Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384.

 

Endovasular treatment is a reasonable option in case of mycotic thoracic aortic aneurysm, taking into consideration the risk of reinfections. Preoperative sepsis control and antibiotic treatment at least for one week may diminish infection related complications and should be considered when feasible.⁷⁶Sörelius K, Wanhainen A, Wahlgren CM, Langenskiöld M, Roos H, Resch T, et al. Nationwide study on treatment of mycotic thoracic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;57(2):239-246. ,⁷⁷Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms. Eur J Vasc Endovasc Surg. 2019;57(1):8-93

 

Antimicrobial treatment

The choice of long-term antimicrobial therapy and treatment duration after AGI- and MAA-repair is complex and multifactorial and should be done in close consultation with infection specialists. Many pragmatic treatment decisions lack extensive support from the literature and some recommendations are extrapolated from research surrounding prosthetic joint infections or infectious endocarditis. The main considerations are:

 

1) Surgical result and choice of conduit: Treatment duration as well as the duration of parenteral antimicrobial treatment is often extended if any prosthetic vascular graft- or endograft is left in-situ, alternatively if an endovascular repair is used as definitive treatment. The choice of biofilm active antimicrobial treatment regimens is many times advisable if applicable under these circumstances.

2) Microbiology: Some pathogens are known to be difficult to eradicate from an established prosthetic graft infection, requiring longer treatment duration to decrease the risk of recurrent infections. Examples include Candida spp and Enterococcal spp ⁷⁸Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, et al. In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother. 2002;46(11):3591-3596. .

3) Presence of primary or secondary aorto/graft-bronchial- or enteric fistulae: The presence of fistulae greatly increases the risk of polymicrobial infections⁷⁹Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. ,⁸⁰Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. . In addition, Candida spp have been isolated from explanted grafts in in up to 30% of AGI patients with a concomitant GEF⁸¹Gavali H, Mani K, Furebring M, Olsson KW, Lindström D, Sörelius K, et al. Editor’s Choice–Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study. Eur J Vasc Endovasc Surg. 2021;62(6):918-926. ,⁸²Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. . As such, it is reasonable to have a low threshold for a broad gram-positive- and negative coverage in in MAA and AGI patients with a diagnosed fistula, as well as initiation of antifungal treatment in the case of an enteric fistula regardless of initial culture results.

 

Biofilm active therapy

A bacteria associated biofilm represents the mesh of pathogen-produced extracellular polymeric matrix with the adherent bacteria and is particularly common in gram-positive foreign body infections⁸³Khatoon Z, McTiernan CD, Suuronen EJ, Mah TF, Alarcon EI. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon. 2018;4(12):e01067. . The biofilm creates a milieu in which the effect of both antimicrobial treatment and the hosts immune response is greatly diminished. This is partly explained by the physical barrier created, but also by the reduced metabolic activity in the bacteria⁸⁴Khatoon Z, McTiernan CD, Suuronen EJ, Mah TF, Alarcon EI. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon. 2018;4(12):e01067. . Rifampicin and Daptomycin are two antibiotics with a gram-positive spectrum shown to have an enhanced effect on biofilm-associated infections in-vitro and reduces the risk of recurrent gram-positive infections in prosthetic joint infections ⁸⁵Tande AJ, Gomez-Urena EO, Berbari EF, Osmon DR. Management of Prosthetic Joint Infection. Infect Dis Clin North Am. 2017;31(2):237-252. ,⁸⁶Telles JP, Cieslinski J, Tuon FF. Daptomycin to bone and joint infections and prosthesis joint infections: a systematic review. Braz J Infect Dis. 2019;23:191-196. . The benefit and effect size of adding these agents in the antimicrobial therapy of MAA- and AGI patients is not fully eluded, but their use in vascular graft infections have increased over time⁸⁷Janko MR, Woo K, Hacker RI, Baril, D., Bath J, Smeds M. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas. Journal of vascular surgery, 2021;73(1):210-221. .

 

Treatment duration and follow-up

As mentioned previously, the optimal antimicrobial treatment duration for MAA and AGI patients is not fully understood. Current European AGI guidelines recommend a minimum of 2 weeks of intra venous (IV) antibiotic treatment after all infected tissue and graft material are removed, followed by up to 4 weeks of an oral regimen. In the setting where replacement with a new prosthetic graft is needed, the recommendation is prolonged to 4-6 weeks of IV antibiotic treatment followed by 3-12 months of oral antibiotic regimen, possibly life-long ⁸⁸Chakfé N, Diener H, Lejay A, Assadian O, Berard X, Caillon J, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections. Eur J Vasc Endovasc Surg. 2020;59(3):339-384(Figure 8).

 

 

In case of EVAR treatment of MAA 4-6 weeks of IV IE-dose regimen of antimicrobial treatment, biofilm-active treatment when applicable, and antifungal treatment in case of an enteric fistula is recommended. This is followed by at least 6-12 months of oral antimicrobial treatment. Continuous laboratory and clinical assessments at a minimum of 1-month intervals. More frequently when any change in therapy is made. Radiological follow-up and molecular imaging (18-FDG-PET/CT) at 6-month intervals or when withdrawal of anti-microbial therapy is considered. Ultimately, a clinical decision must be made in each case balancing the risks of recurrent infection with the potential side effects of a prolonged antimicrobial treatment. A suggested pragmatic decision-making strategy is summarised in Figure 9.

 

Conservative treatment in MAA and AGI

In patients unfit for surgical repair due to frailty, comorbidities or anatomical complexity including thoracic and suprarenal involvement of the MAA or AGI, a conservative or semi-conservative treatment strategy can be the only feasible option. This includes the use of life-long antimicrobial suppressive treatment, percutaneous or surgical debridement of any easily accessible paraaortic infected tissue or abscess and the potential use of endovascular adjuncts in selected AGI-cases.

 

Several studies have shown the inferiority of conventional conservative treatment in older AGI cohorts in terms of recurrent infection risk as well as overall mortality⁸⁹Li HL, Chan YC, Cheng SW. Current evidence on management of aortic stent-graft infection: a systematic review and meta-analysis. Ann Vasc Surg. 2018;51:306-313. ,⁹⁰Lin CH, Hsu RB. Primary infected aortic aneurysm: clinical presentation, pathogen, and outcome. Acta Cardiol Sin. 2014;30(6):514. However, due to the endovascular evolution causing an epidemiological shift in terms of endograft vs graft infections, increased frequency of complex branched/fenestrated endografts at risk for future infection, as well as advancements in biofilm active antimicrobial treatment strategies this may need to be reassessed in the future.

 

In patients with MAA, medical treatment alone without any aneurysm-specific treatment have shown aneurysm-related mortality in excess of 70%⁹¹Lin CH, Hsu RB. Primary infected aortic aneurysm: clinical presentation, pathogen, and outcome. Acta Cardiol Sin. 2014;30(6):514.

 

In selected patients with limited localised graft infections a semi-conservative (SC), graft preserving, strategy may be considered. This includes surgical debridement of adjacent infected tissue with partial resection of the infected graft followed by medical antimicrobial treatment. A recent large multi-centre study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula⁹²Janko M, Hubbard G, Woo K, Kashyap VS, Mitchell M, Murugesan A, et al. Contemporary Outcomes After Partial Resection of Infected Aortic Grafts. Ann Vasc Surg. 2021;76:202-210.

MAA

The mortality rates differ widely in the literature depending on bacteriology, location of the MAA and type of repair. When feasible, reconstructions with biological vascular grafts have superior outcome, in terms of infection related mortality and reinfection, over prosthetic grafts.

 

In general, OSR in the arch and abdominal paravisceral segment of the aorta are associated with the highest early (90-day) mortality reported in the range of 10-60% and 20-60% respectively¹Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. ,²Hsu RB, Chang CI, Chan CY, Wu IH. Infected aneurysms of the suprarenal abdominal aorta. J Vasc Surg. 2011;54(4):972-978. ,³Hsu RB, Lin FY. Infected aneurysm of the thoracic aorta. J Vasc Surg. 2008;47(2):270-276. . For the infrarenal MAA outcomes for both treatment modalities are generally more favourable with an early mortality rate for OSR: 5-10% and EVAR: 5-10% ⁴Chan FY, Crawford ES, Coselli JS, Safi HJ, Williams Jr TW. In situ prosthetic graft replacement for mycotic aneurysm of the aorta. Ann Thorac Surg. 1989;47:193-203. ,⁵Reddy DJ, Shepard AD, Evans JR, Wright DJ, Smith RF, Ernst CB. Management of Infected Aortoiliac Aneurysms. Arch Surg. 1991;126(7):873–879. ,⁶Luo CY, Ko WC, Kan CD, Lin PY, Yang Y J. In situ reconstruction of septic aortic pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up. J Vasc Surg. 2003;38(5):975-982. ,⁷Sörelius K, Mani K, Björck M, Sedivy P, Wahlgren CM, Taylor P, et al.. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation. 2014;130(24):2136-2142. , ⁸Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. ,⁹Yu SY, Hsieh HC, Ko PJ, Huang YK, Chu JJ, Lee CH. Surgical outcome for mycotic aortic and iliac anuerysm. World J Surg. 2011;35(7):1671-1678. ,¹⁰Heinola I, Sörelius K, Wyss TR, Eldrup N, Settembre N, Setacci C, et al. Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study. J Am Heart Assoc. 2018;7(12):e008104. Regardless of aortic segment involved or surgical technique the frequency of infectious related complication – including development of AGI, recurrent MAA or sepsis – appear to be relatively stable at around 20-30% ¹¹Sörelius K, Budtz-Lilly J, Mani K, Wanhainen A. Systematic review of the management of mycotic aortic aneurysms. Eur J Vasc Endovasc Surg. 2019;58(3):426-435. .

 

Risk factors associated with mortality after MAA repair that are consistent in the literature includes: old age, suprarenal involvement, and development of infectious related complications ¹²Sörelius K, Mani K, Björck M, Sedivy P, Wahlgren CM, Taylor P, et al.. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation. 2014;130(24):2136-2142. ,¹³Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, et al. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015;61:965-71, ¹⁴Yu SY, Hsieh HC, Ko PJ, Huang YK, Chu JJ, Lee CH. Surgical outcome for mycotic aortic and iliac anuerysm. World J Surg. 2011;35(7):1671-1678. ,¹⁵Kan CD, Lee HL, Luo CY, Yang YJ. The efficacy of aortic stent grafts in the management of mycotic abdominal aortic aneurysm—institute case management with systemic literature comparison. Ann Vasc Surg. 2010;24(4):433-440. ,¹⁶Hsu RB, Chen RJ, Wang SS, Chu SH. Infected aortic aneurysms: clinical outcome and risk factor analysis. J Vasc Surg. 2004;40(1):30-35. ,¹⁷Luo CM, Chan CY, Chen YS, Wang SS, Chi NH, Wu IH. Long-term outcome of endovascular treatment for mycotic aortic aneurysm. Eur J Vasc Endovasc Surg. 2017;54(4):464-471. In the setting of an abdominal MAA, EVAR has been shown to be associated with a lower early, up till four years, mortality rate compared to OSR¹⁸Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, et al. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015;61:965-71,¹⁹Kan CD, Lee HL, Luo CY, Yang YJ. The efficacy of aortic stent grafts in the management of mycotic abdominal aortic aneurysm—institute case management with systemic literature comparison. Ann Vasc Surg. 2010;24(4):433-440. , but similar long-term infection related mortality. Additionally, both prolonged antimicrobial therapy ≥3 days prior to surgical treatment and prolonged antibiotic therapy >6 months after surgical repair are associated with lower overall mortality²⁰Saleem BR, Berger P, Vaartjes I, de Keizer B, Vonken EJ, Slart RH, et al. Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection. J Vasc Surg. 2015;61:965-71,²¹Kan CD, Lee HL, Luo CY, Yang YJ. The efficacy of aortic stent grafts in the management of mycotic abdominal aortic aneurysm—institute case management with systemic literature comparison. Ann Vasc Surg. 2010;24(4):433-440. .

AGI

Untreated symptomatic AGI are invariably fatal²²Wilson WR, Bower TC, Creager MA, Amin-Hanjani S, O’Gara PT, Lockhart PB, et al. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Council on Peripheral Vascular Disease; and Stroke Council. Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association. Circulation. 2016;134:e412-e460. . The early survival rate of surgically treated AGI patients is currently 90% and estimated 5-year survival 50%–60%. Prosthetic reconstructions yield better short-term results, but reinfections are more common (11% vs 5%) therefore long-term outcome remains inferior to ISR with biological material²³Chaufour X, Gaudric J, Goueffic Y, Khodja RH, Feugier P, Malikov S, et al; AURC (French University Surgeons Association) collaborators. A multicenter experience with infected abdominal aortic endograft explantation. J Vasc Surg. 2017;65:372-380,²⁴Smeds MR, Duncan AA, Harlander-Locke MP, Lawrence PF, Lyden S, Fatima J, et al. Treatment and outcomes of aortic endograft infection. J Vasc Surg. 2016;63(2):332-340. ,²⁵Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,²⁶Batt M, Feugier P, Camou F, Coffy A, Senneville E, Caillon J, et al; Research Group for Vascular Graft Infection. A Meta-Analysis of Outcomes After In Situ Reconstructions for Aortic Graft Infection.Angiology. 2018;695:370-379,²⁷O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg. 2006;44:38-45,²⁸Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,²⁹Minga Lowampa E, Holemans C, Stiennon L, Van Damme H, Defraigne JO. Late Fate of Cryopreserved Arterial Allografts. Eur J Vasc Endovasc Surg. 2016;52(5):696-702. Early mortality is higher among EVAR explant patients – 25-35% – possibly due to surgical technical difficulties caused by suprarenal hooks, suprarenal clamping, and aggressive clinical course of infection³⁰Argyriou C, Georgiadis GS, Lazarides MK, Georgakarakos E, Antoniou GA. Endograft Infection After Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis. J Endovasc Ther. 2017;24:688-697,³¹Capoccia L, Speziale F, Menna D, Esposito A, Sirignano P, Rizzo AR, et al. Collaborators; Preliminary Results from a National Enquiry of Infection in Abdominal Aortic Endovascular Repair (Registry of Infection in EVAR–R.I.EVAR). Ann Vasc Surg. 2016;30:198-204,³²Oltean M, Herlenius G, Gäbel M, Friman V, Olausson M. Infectious complications after multivisceral transplantation in adults. Transplant. 2006;38:2683-2685,³³Schaefers JF, Donas KP, Panuccio G, Kasprzak B, Heine B, Torsello GB, et al. Outcomes of Surgical Explantation of Infected Aortic Grafts After Endovascular and Open Abdominal Aneurysm Repair. Eur J Vasc Endovasc Surg. 2019;57:130-136.

 

Patients with AEE/AEF carry the worst prognosis. They are often nutritionally depleted and immunologically compromised, or present with acute haemorrhage and sepsis resulting in early mortality of 20-40%. ³⁴Chaufour X, Gaudric J, Goueffic Y, Khodja RH, Feugier P, Malikov S, et al; AURC (French University Surgeons Association) collaborators. A multicenter experience with infected abdominal aortic endograft explantation. J Vasc Surg. 2017;65:372-380,³⁵Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,³⁶Heinola I, Kantonen I, Jaroma M, Albäck A, Vikatmaa P, Aho P, et al. Editor’s Choice – Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. Eur J Vasc Endovasc Surg. 2016;51(2):232-9,³⁷Oderich GS, Bower TC, Cherry KJ Jr, Panneton JM, Sullivan TM, Noel AA, et al. Evolution from axillofemoral to in situ prosthetic reconstruction for the treatment of aortic graft infections at a single center. J Vasc Surg. 2006;43:1166-74. Infection is usually polymicroabial and often including Candida, which leads to poorer survival. Therefore, antifungal medication is recommended once AEE/AEF is diagnosed.³⁸Lejay A, Monnot A, Georg Y, Colvard B, Thaveau F, Geny B, et al. Pathology of graft and stent-graft infections: Lessons learned from examination of explant materials. Semin Vasc Surg. 2017;30:70-74,³⁹Ali AT, Modrall JG, Hocking J, Valentine RJ, Spencer H, Eidt JF, et al. Long-term results of the treatment of aortic graft infection by in situ replacement with femoral popliteal vein grafts. J Vasc Surg. 2009;50:30-9,⁴⁰Heinola I, Sörelius K, Wyss TR, Eldrup N, Settembre N, Setacci C, et al. Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study. J Am Heart Assoc. 2018;7(12):e008104 Among in-hospital survivals, the late mortality is comparable to AGI patients without AEE/AEF.