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Mycotic Aneurysm
Introduction
A mycotic aneurysm is a dilatation of an arterial wall due to an infectious process. The term "mycotic" was coined by William Osler in his Gulstonian Lectures, where he described a man with multiple aortic mycotic aneurysms that resulted from cardiac valve vegetation, resembling a fleshy fungus.[1] However, this description does not suggest a fungal etiology, as the majority of infected aneurysms are caused by bacterial pathogens. Infectious aortitis refers to a vascular infection without aneurysmal dilation. An infected aneurysm usually develops in the presence of a preceding systemic infection with bacteremia or through direct invasion of the blood vessel wall in a preexisting aneurysm or atheromatous plaque.[2]
The risk of a mycotic aneurysm is higher in immunocompromised individuals, including those with HIV infection, diabetes mellitus, or malignancy, as well as those receiving high-dose glucocorticoids or chemotherapy.[3][4][5] The most commonly affected blood vessels, in order of frequency, include the aorta, intracranial vasculature, and femoral and visceral arteries (eg, superior mesenteric and splenic).[6][7] The natural history of these aneurysms is characterized by expansion, leading to pseudoaneurysm formation, where rupture is contained, followed by eventual rupture, hemorrhage, sepsis, and multiple organ failure. Mycotic aneurysms are among the most challenging clinical problems for vascular surgeons due to their associated perioperative mortality.[8]
Etiology
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Etiology
Several factors are implicated in the pathogenesis of mycotic aneurysms, including bacteremia, vessel injury with bacterial inoculation, local bacterial spread, and septic emboli. Vascular injury predisposes the intima to infection from bacterial seeding. This process is particularly common in older patients with atherosclerosis or preexisting aneurysms who experience sepsis or bacteremia. The aorta is the most frequently affected vessel due to the high prevalence of atherosclerosis and aneurysm formation in this structure.
Vascular injury resulting from intravenous drug abuse, trauma, or iatrogenic percutaneous interventions can lead to the direct inoculation of bacteria into the blood vessel wall. The blood vessels most commonly affected in this manner include the femoral, common iliac, subclavian, and carotid arteries. Direct extension of an infection to an artery can cause inflammation, as seen in conditions such as vertebral osteomyelitis and abdominal infections such as appendicitis, cholecystitis, and pyelonephritis. Emboli from the vasa vasorum can also trigger inflammation of the blood vessel wall, contributing to infective endocarditis and subsequent mycotic aneurysm formation. These emboli are typically multiple and often involve intracranial vessels at branch points.[4][9]
Epidemiology
Infectious aortic aneurysms are rare, with an incidence of 0.7% to 3% and a median age of onset of around 65.[10][11] These aneurysms are more common in men due to their higher incidence of atherosclerosis compared to women, with an increased risk in individuals who smoke or have diabetes mellitus. The arteries most commonly involved include the femoral, aorta, splanchnic arteries (superior mesenteric, hepatic, and splenic), and cerebral arteries.
In Western countries, the most common bacterial pathogens responsible for mycotic aneurysms are Staphylococcus aureus (28%), Salmonella spp. (15%), and Pseudomonas aeruginosa (10%), with Salmonella spp. being more commonly reported in Asian countries.[8] Coronary mycotic aneurysms have been reported after cardiac stent placement, while renal artery mycotic aneurysms have been seen in renal transplant recipients.[12] Intracranial mycotic aneurysms develop in 2% to 10% of infective endocarditis cases, with a higher prevalence in left-sided cardiac involvement.[13]
Pathophysiology
Arterial injury, combined with bacterial seeding, leads to infection of the intima. Once the vessel wall is involved, the infection rapidly spreads to the deeper vascular layers, resulting in the formation of an aneurysm.[14] Bacterial infection triggers the release of proinflammatory cytokines, which attract neutrophils. These cells activate matrix metalloproteinases, which contribute to the focal breakdown of the blood vessel wall. Some studies suggest that the degree of metalloproteinase activity correlates with the risk of future aneurysm rupture and may serve as an important prognostic indicator.[15]
Microbiology
Cultures of the aortic wall are positive in 50% to 85% of mycotic aneurysm cases.[10][3] The most commonly cultured pathogens included S aureus (28% to 71%) [6][16] and Salmonella spp. (15%).[8] Other isolated organisms include Treponema pallidum, Mycobacterium spp., P aeruginosa, Listeria monocytogenes, Klebsiella pneumoniae, Escherichia coli, Clostridium ramosum, Campylobacter jejuni, Haemophilus influenzae, Yersinia pseudotuberculosis, Acinetobacter lwoffi, Brucella spp., and Nocardia otitidiscaviarum.[17][18][19][20][21][22][23][24][25][26][27][4] Fungal pathogens are rarely identified except in immunosuppressed patients, such as those with diabetes mellitus or HIV infection, individuals undergoing systemic chemotherapy, or cases of disseminated fungal infection.[28][5]
Histopathology
Histological analysis of intraoperative tissue samples reveals transmural inflammation, necrosis, thrombosis, and abscess formation.[29] In the majority of cases, the tissue samples stain positive for bacteria.[2]
History and Physical
The clinical presentation of a mycotic aneurysm depends on the location of the aneurysm, the severity of the infection, and the patient's comorbidities.[30] Risk factors associated with an infected aneurysm include an immunocompromised state, intravenous drug use, invasive vascular procedures, and a history of endocarditis.[13]
The most common clinical manifestations include fever, a pulsatile mass, back pain when the aorta is involved, headaches with intracranial vessel involvement, and inflammation at the arterial site.[8][9] Due to the nonspecific nature of these symptoms, many patients are evaluated for fever of unknown origin. They are not diagnosed until severe complications such as sepsis, thrombosis, hemorrhage, or rupture develop.
Local expansion of the infectious process involving the aorta may lead to psoas abscess formation, presenting with flank pain, limping, and fever, or it may result in vertebral osteomyelitis.[27] Dysphagia and hoarseness can occur if the laryngeal nerve is impinged.[28] Pulmonary artery involvement has been associated with hemoptysis.[31][32]
The formation of an aortoduodenal fistula may lead to high-output cardiac failure or the development of an expanding hematoma.[33][34] Local vascular inflammation can result in a tender indurated mass and bruit on physical examination in 50% of cases.[16] Cerebral aneurysms usually present with symptoms of stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.[4][5][13]
Evaluation
The presence of risk factors in the medical history, along with clinical findings, should prompt further evaluation for mycotic aneurysms. As there is no definitive diagnostic algorithm or specific criteria for diagnosis, a combination of clinical, laboratory, imaging, and intraoperative findings will help support the diagnosis of an infected aneurysm. The clinical presentation will often include fever, localized physical findings, an immunosuppressed state, a history of atherosclerosis risk factors, and a concurrent infection. Laboratory findings commonly include elevated inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count, and positive blood cultures.[3] Positive bacterial cultures of involved vessels are found in 50% to 85% of cases.[6] Culture-negative infective endocarditis has also been reported in cases of cerebral mycotic aneurysms.[13]
Radiological findings are the most sensitive and specific indicators to demonstrate the presence of a mycotic aneurysm. Highly suggestive findings include saccular and lobulated vessel contours, soft tissue inflammation around the vessel wall, manifested as perivascular contrast enhancement, intramural air or a collection of air around the blood vessel, and a perianeurysmal fluid collection.[35][36][37][38]
A contrast-enhanced computed tomography (CT) scan is the initial imaging modality of choice for demonstrating aortic aneurysms, although contrast-enhanced magnetic resonance angiography is a suitable alternative. Both CT and magnetic resonance imaging (MRI) have moderately high sensitivities and specificities for detecting mycotic aneurysms.[39] Digital subtraction angiography can also provide the same radiological information despite being a more invasive study.[30] Transthoracic echocardiography is the preferred imaging modality for coronary aneurysms.[40] Nuclear medicine scans are primarily used to detect graft infection.[41][42]
Patients with infectious endocarditis may have multiple aneurysms, necessitating additional imaging studies and a more extensive angiographic evaluation. Monitoring the response to antibiotic therapy is done by repeating serial inflammatory markers and imaging studies before and after definitive surgery.
Treatment / Management
All patients will require prolonged antibiotic therapy, which should be determined based on culture and sensitivity results. A 6- to 8-week course of medical therapy is recommended, although the duration of treatment may be extended if there is evidence of persistent infection.[41] The response to therapy is monitored through serial white blood cell counts, inflammatory markers, and the resolution of fever and hemodynamic stability. Empiric antibiotics often include vancomycin combined with an agent effective against gram-negative organisms such as Salmonella spp., such as ceftriaxone, a fluoroquinolone, or piperacillin-tazobactam.(B3)
Definitive management usually requires the surgical removal of all infected tissue. Surgical debridement with or without revascularization via an endovascular approach or open procedure, which can include ligation, resection, or bypass. An extra-anatomic bypass or in-situ graft insertion is often necessary. The choice of procedure depends on factors such as the location of the aneurysm, the extent of the infection, the patient’s medical condition, and the surgeon’s preference.
In general, proximal ligation and resection of the aneurysm are appropriate for peripheral arteries and splanchnic vessels. Homografts using segments of medium-sized vessels, such as the iliac artery or saphenous vein, are suitable for renal, visceral, carotid, or femoral arteries. Larger vessels, such as the aorta with minimal purulence, are managed through reconstruction using an in-situ graft, with the conduit covered by an omental pedicle to minimize the risk of persistent infection.
No consensus exists on the ideal graft, with options including a rifampin-soaked dacron graft, cryopreserved aortic graft, or femoral vein graft. Persistent purulence, systemic signs of inflammation, or extensive aortic or paraaortic purulence suggest the need for an extra-anatomic bypass. Long-term antimicrobial suppression therapy is considered if an emergency surgical procedure is performed for graft placement in an infected surgical site.
Cerebral mycotic aneurysms are typically treated using endovascular techniques such as coil embolization, Onyx, or N-butyl-2-cyanoacrylate embolization, with the goal of obliterating the involved blood vessel.[43] The aneurysm occlusion success rate was 97% in 12 of 14 studies.[44] In some cases, direct surgical clipping or vascular bypass surgery may be used as an alternative treatment for cerebral mycotic aneurysms.[9][5](A1)
Perioperative mortality for open surgery is high (approximately 20%),[45][3] leading to increasing interest in the development and use of endovascular therapies. These therapies offer a suitable alternative for patients with high perioperative risk or as a bridging procedure before definitive repair can be performed in those with severe sepsis.[30][46] Although some studies demonstrate higher early mortality rates with open surgery compared to endovascular repair, long-term outcomes are generally comparable.[47][48] Infections occurring after endovascular or open repair should be treated with systemic antibiotics.[30](B2)
Differential Diagnosis
The differential diagnosis for mycotic aneurysms can vary based on the involvement of different organ systems. An atherosclerotic aortic aneurysm typically presents with fusiform enlargement, calcification, and a slow clinical course, often without fever or systemic signs of infection. A renal artery mycotic aneurysm in a transplanted kidney may be associated with pyelonephritis. Vasculitides can cause inflammatory aortitis and aneurysm formation. An intracranial mycotic aneurysm can present symptoms similar to meningitis, orbital cellulitis, or septic thrombophlebitis.
Toxicity and Adverse Effect Management
Long-term antimicrobial therapy can lead to antibiotic-related adverse effects, such as tendinopathy with fluoroquinolones or nephrolithiasis associated with ceftriaxone.
Prognosis
Survival depends on the location of the aneurysm. Infected aortic aneurysms generally have poor outcomes, with untreated aortic aneurysms being almost universally fatal. Prognostic indicators of a poor clinical outcome include female gender, hemodynamic instability, shock or fever at the time of surgery, an immunosuppressed state, and extensive involvement of the aorta and periaortic areas.[3] Endovascular repair has shown better survival rates compared to open surgical repair in experimental studies.[47][48][49][44]
Long-term outcomes are closely related to the chosen treatment approach. However, the overall survival for patients who respond to medical therapy is generally good, with no significant long-term disabilities. In contrast, patients with persistent infection or graft reinfection have a poor prognosis, with a mortality rate approaching 100% without graft removal.
Complications
Untreated aneurysms carry a significant risk of rupture (approximately 60%), sepsis, thrombosis, distal ischemia, or multiple organ failure.
Complications associated with surgical repair include prolonged operating time, which may result in distal ischemia such as myocardial infarction, cerebrovascular accident, ischemic bowel, or acute kidney injury. Delayed complications of in-situ grafts include reinfection, graft failure, and paraaortic leaks due to anastomotic failure or fistula formation. In-situ graft infections are associated with a 100% mortality rate within 2 years if the graft is not removed.[30]
The extra-anatomic bypass procedure has fewer intraoperative complications, but the majority of patients eventually develop limb ischemia or severe claudication.[30]
Postoperative and Rehabilitation Care
Perioperative mortality rates for open surgery can approach 20%, and postoperative complications can occur in 60% of cases. These complications include distal ischemia, amputation, renal failure, respiratory failure requiring prolonged mechanical ventilation, and multiple organ failure.[50][3]
Complications associated with extra-anatomic bypass procedures include aortic stump disruption, amputation, and reinfection.[48]
Regarding rehabilitation care, many studies report prolonged hospitalization (median approximately 58 days) after surgery. Many patients require extended physical and occupational therapy, along with a gradual return to baseline activity.[51]
Consultations
The infectious disease consultation service should be involved in the clinical management of complicated cases or infections caused by multiple drug–resistant organisms.
Deterrence and Patient Education
Patients are advised to remain in the hospital until there is an improvement in clinical symptoms or resolution of fever and sepsis. Patients should stay in the ICU during the early postoperative phase for close monitoring. They should be educated about the risks and complications of the procedure, as well as alternative treatment options. Prolonged antibiotic therapy is required for these patients, with some authors suggesting lifelong treatment. Therefore, comprehensive patient education is essential for ensuring adherence to the therapy and understanding the long-term management plan.
In the postoperative period, patients should wear loose clothing that does not irritate the incision site. Patients should avoid soaking in a bathtub, hot tub, or swimming pool shortly after surgery. The incision should be cleaned with soap and water daily until wound epithelialization occurs. Dressings should be changed frequently. Lotions, creams, and herbal remedies should not be applied to the wound. A gradual return to activity is recommended to promote healing. As most patients are in an older age group, physiotherapy and occupational therapy may be required to aid in recovery.
As mycotic aneurysms are associated with atherosclerosis, aggressive modification of risk factors is recommended for these patients. This includes following the DASH diet, smoking cessation, aspirin use, and statin therapy.
Enhancing Healthcare Team Outcomes
Mycotic aneurysms are rare and have a fulminant course. The exact incidence remains poorly studied, with most data derived from case series and summaries. However, evidence suggests that the incidence has increased over the last 2 decades, likely due to a rise in 2 key risk factors—atherosclerosis and immunosuppression.[52] The pathogenesis is complex, involving a combination of risk factors and bacterial infection of the vessel wall. Diagnosing mycotic aneurysms is challenging due to their nonspecific clinical features, which can resemble more benign conditions, such as spinal degeneration or a urinary tract infection in a patient with an aortic aneurysm.
Management is challenging due to the invasive nature of the required surgical interventions and the comorbidities that predispose patients to infection. Medical therapy alone is associated with a 50% mortality rate, and most experts recommend combining surgical intervention with prolonged antimicrobial therapy. Vascular procedures are considered high-risk for vulnerable patients and demand a high level of skill and coordination among the healthcare team. Most cases are initially managed by the hospitalist or general surgeon. However, it is advisable to involve a vascular surgeon and infectious disease specialist early in the clinical course to minimize any potential delays in intervention. Postoperative care depends significantly on nursing, pharmacy, and physical and occupational therapies.
The high mortality and morbidity rates associated with mycotic aneurysms are primarily due to the extent of the infection at the time of diagnosis. Therefore, maintaining a high index of suspicion and obtaining an early diagnosis may improve patient outcomes. The lack of standardized criteria for diagnosis and management also contributes to variability in clinical outcomes across different studies. A consensus statement from professional societies could help address this concern.
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