on 01-Feb-2021 (Mon)

An aneurysm is an abnormal focal arterial dilation

The name mycotic aneurysm was coined by Osler to describe aneurysms associated with bacterial endocarditis [1]. These were noted to have the appearance of "fresh fungus vegetations"; however, the majority of mycotic aneurysms are caused by bacteria

Although some authors use the term "mycotic" to describe infected aneurysm regardless of etiology, we will limit the use of this term to those aneurysms that develop when material originating in the heart causes arterial wall infection and, subsequently, dilation [2]

Aneurysms are classified into true and false, or pseudoaneurysms. True aneurysms involve all three layers of the arterial wall (intima, media, and adventitia). A false, or pseudo-, aneurysm is a collection of blood or hematoma that has leaked out of the artery but is then confined by the surrounding tissue

Arterial injury – Arterial injury is an important risk factor for an infected aneurysm. Artery injury resulting in infected femoral artery pseudoaneurysm is commonly due to intravenous drug use (self-inflicted), but iatrogenic mechanisms, such as invasive monitoring, percutaneous access for cardiac catheterization, or other peripheral interventions, can also lead to infected aneurysm [3,4]. Arterial injury may result from other mechanisms, such as gastrointestinal perforation [5,6] or peripheral nerve block [7]. (See 'Direct bacterial inoculation' below.)

Antecedent infection – In a retrospective review, nearly half of 43 patients with an infected aortic aneurysm were found to have an antecedent infection that included pneumonia, cholecystitis, urinary tract infection, endocarditis, diverticulitis, soft tissue infection, and osteomyelitis. In the pre-antibiotic era, the majority of infected aneurysms were due to endocarditis. More contemporary series identify endocarditis as the likely etiology in 17 to 29 percent of cases [8,9]. The rapid development of an infected aortic aneurysm associated with periodontal infection and oral surgery has also been reported [10-13]. (See 'Septic emboli (mycotic aneurysm)' below.)

Impaired immunity – Immunosuppressive states predispose the patient to infection, which may present with atypical clinical features. Immunosuppressive disorders were found in 70 percent of patients with infected aneurysms in a review of 43 patients [14]. Diabetes, alcoholism, chronic glucocorticoid therapy, chemotherapy, and malignancy have been identified as possible risk factors for infected aneurysm [14-18]. Immune mechanisms may play a role in the development of infected aneurysm in a variety of other circumstances, such as in patients with cancer [19], cirrhosis [20], those undergoing hemodialysis [21], following gastrointestinal endoscopy [22], posttransplant, those with HIV infection [23-25], and following trauma or near drowning [26]. (See 'Bacteremic seeding' below.)

Atherosclerosis – Patients with atherosclerosis, particularly older adults, are at risk for bacteremic seeding of atheromatous plaques. (See 'Bacteremic seeding' below.)

Preexisting aneurysm – Preexisting aneurysms are at risk for secondary infection due to bacteremia or spread from a contiguous infection. The prevalence of infection in a preexisting aneurysm is low. In a study that cultured aortic tissue from patients undergoing elective aneurysm repair, positive cultures were obtained in 33 of 88 patients [27]. Positive cultures were associated with subsequent infected grafts in three patients. However, the majority of patients with positive aortic cultures had no known negative sequelae

Direct bacterial inoculation — Direct inoculation of bacteria into the arterial wall can occur at the time of vascular injury. An arterial injury may be self-inflicted, iatrogenic, accidental, or due to assault (gunshot, stab). Infected pseudoaneurysm following arterial injury has become one of the most common forms of infected aneurysm. The femoral artery is the most commonly involved arterial site.

Bacteremic seeding — Bacteremic seeding of an existing intimal injury, atherosclerotic plaque, or preexisting aneurysm can lead to arterial wall infection.

The intima is normally highly resistant to infection, but, when diseased, it allows bacteria to pass through it into deeper layers of the arterial wall. Once a local infection is established, suppuration, localized perforation, and pseudoaneurysm can result. The aorta is the most common location affected primarily since it is the most frequent site of atherosclerosis, but peripheral arteries can also be affected. Infected aneurysm can occur in the absence of significant atherosclerosis [28].

In a similar manner, preexisting aneurysms may become secondarily infected, which may predispose to rupture. In a study of 80 patients undergoing open aortic repair, a greater number of positive cultures were found in patients with ruptured aneurysms compared with asymptomatic and symptomatic aneurysms (38 versus 9 and 13 percent, respectively) [29].

Contiguous infection — A focus of infection can extend to the arterial wall. Extension of a postoperative infection can lead to an infected aneurysm and has been described in the setting of appendectomy [30], cholecystectomy [31], colorectal surgery [32,33], as a result of pancreatic pseudocyst [34], and following knee or hip replacement surgery [35-37]. Extension of infection not related to surgery can also occur as seen in vertebral osteomyelitis [38-40]

Septic emboli (mycotic aneurysm) — Septic embolic from the heart can occlude the vasa vasorum of the vessel or the vessel lumen, leading to vascular wall infection and mycotic aneurysm formation. Embolism is estimated to occur in between 25 and 50 percent of patients, but only about 1 to 5 percent develop symptomatic mycotic aneurysm [41]. Because of their embolic nature, mycotic aneurysms tend to be multiple, but they can also be solitary [42]. Spontaneous resolution with antibiotic therapy for endocarditis has been reported [43-45]. As such, the true prevalence of mycotic aneurysm is unknown

Mycotic aneurysms can develop anywhere but are most commonly seen in the intracranial arteries, followed by visceral arteries and upper or lower extremity arteries, typically occurring at arterial bifurcations [41]. One study included 151 patients with endocarditis who underwent cerebral angiography as a part of preoperative evaluation; a mycotic aneurysm was found in seven (4.6 percent) of these patients [46]. Mycotic aneurysms of coronary arteries, although rare, have also been described [47]. In one review including 922 cases of definite infective endocarditis, symptomatic peripheral mycotic aneurysm was observed in 2 percent of cases; of these, 66 percent were intracranial (in the region of the middle cerebral artery) and 34 percent were extracranial [42]. Six peripheral artery aneurysms were identified; two in popliteal and one each in the ulnar artery, humeral artery, hepatic artery, and coronary artery

Blood cultures are positive in 50 to 85 percent of cases [48,49]. Organisms have been isolated from aneurysmal tissue in up to 76 percent of patients [29,48]. In one case series, multiple organisms were isolated in 8 percent, and no pathogen was identified in 25 percent of cases [8]. Identification of the causative organism using molecular methods (bacterial 16S ribosomal RNA) has been described [50]

Although bacteriologic patterns continue to evolve over time, the organisms with the greatest affinity for the arterial wall, Staphylococcus spp and Salmonella spp, remain the most common [51-53]. Staphylococcus aureus is the most common pathogen reported in 28 to 71 percent of cases [8,48]

Salmonella is reported in 15 to 24 percent of cases [8,51]. The diseased aorta appears to be vulnerable to Salmonella, and this pathogen is frequently isolated in infected aneurysms due to bacteremic seeding of atherosclerotic plaque [58].

Streptococcus pneumoniae was a frequent etiology of infected aneurysms in the pre-antibiotic era but became rare with the advent of penicillin; however, S. pneumoniae may be reemerging as a cause of infected aneurysms [59,60].

Other gram-negative organisms are also associated with bacteremic seeding [32,61-63]. In one study, although gram-positive organisms predominated, gram-negative organisms were seen in 35 percent of cases [63]. In this study, gram-negative infections were associated with a higher incidence of aneurysm rupture (84 versus 10 percent) and mortality (84 versus 50 percent) compared with gram-positive organisms.

Less common causes of infected aneurysm include Treponema pallidum and Mycobacterium spp including Mycobacterium bovis BCG [64-68]. Syphilis (T. pallidum) once caused up to 50 percent of infected aneurysms (image 1). Tuberculosis is a rare cause of infected aneurysms and is most often due to erosion of periaortic lymph nodes into the aortic wall. One review of cases of infected aneurysm caused by Mycobacterium tuberculosis found only 41 cases between 1945 and 1999 [69].

Coxiella burnetii can also be the cause of an infected aneurysm [70-74]. A C. burnetii–infected aneurysm can occur without other manifestations of chronic Q fever [70].

Fungal arterial infections are also rare but may occur in patients with immune suppression, diabetes mellitus, or following treatment of a disseminated fungal disease. Pathogens include Candida [75], Cryptococcus [76], Aspergillus [77], Pseudallescheria boydii [26], and Scedosporium apiospermum [78].

Their choice of landmark time points was baseline, 3 years, 4 years, 5 years, and 7 years, a data-driven choice based on exponential curves that best fit the observed survival curve.

To estimate hazard ratios, we log-transformed variables with skewed distributions; these included albumin, creatinine, LDH, and SB2M.

The classic presentation of an infected aneurysm is a painful, pulsatile, and enlarging mass together with systemic features of infection, such as fever. This presentation is more likely to be found for infected aneurysms that are superficial in location (eg, common femoral artery). In one series of 52 infected aneurysms among intravenous drug users, a tender indurated mass was palpated in 92 percent of cases; these were pulsatile in 52 percent of cases [48]. A bruit was heard in 50 percent of cases, fever was observed in 48 percent, and there was bleeding at the injection site in 15 percent of cases

In some cases, infected aneurysm may be masked by overlying inflammation. Thus, the presence of a soft tissue infection in association with a major blood vessel should raise suspicion for an infected aneurysm. Infected aneurysm can be easily misdiagnosed as cellulitis, abscess, or thrombophlebitis

Infected aneurysms involving the aorta or iliac arteries may be accompanied by abdominal or back pain. On the other hand, patients with infected aortic aneurysm may manifest only with fever of unknown origin, some of whom will remain undiagnosed until rupture.

Inflammatory aneurysms are characterized by an inflammatory infiltrate in the aortic adventitia associated with adventitial fibrosis. Diagnostic signs on abdominal computed tomography (CT) help to differentiate these

Infected aneurysm of the intracerebral vessels may present as stroke or subarachnoid hemorrhage, particularly in the setting of endocarditis.

The diagnosis of an infected aneurysm is based upon imaging the aneurysm, and infection is confirmed by culturing an organism from the blood. Computed tomographic (CT) angiography definitively diagnoses the aneurysm, specific features suggest infection, and CT also simultaneously evaluates the status of the circulation [117]

On laboratory examination, an increased white blood cell count is found in 64 to 71 percent of patients [51,118,119]. Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are generally elevated.

Blood cultures (aerobic, anaerobic, fungal) should be obtained in any patient with a suspected infected aneurysm. Because blood culture may be negative in 25 to 50 percent of patients, negative blood cultures alone are not sufficient to rule out infected aneurysm.

An infected aneurysm may be first suspected in the operating room based upon purulence in association with a preexisting aneurysm [120]. Tissue samples of the aneurysm wall should be sent for culture (aerobic, anaerobic, fungal) and Gram stain. In the operating room, a negative Gram stain is not sufficient to exclude a diagnosis of infected aneurysm [118]. Conversely, positive tissue cultures in the absence of clinical findings do not confirm an infected aneurysm in the absence of appropriate clinical findings. In one study, 69 percent of patients had positive preoperative blood cultures and 92 percent had positive aneurysm wall cultures, but the operative Gram stain was positive in only 50 percent of patients with ruptured infected aneurysms and 11 percent of unruptured but infected aneurysms [118].

Imaging studies for detection of intracranial mycotic aneurysm include CT angiography, magnetic resonance (MR) angiography, and digital subtraction angiography (DSA) [41]. Of these, CT angiography is the most useful for diagnosing infected aneurysm [121]. MR angiography is an alternative diagnostic study when intravenous contrast is contraindicated [122]. When vascular imaging is consistent with an infected aneurysm, we prefer to perform additional imaging of the remainder of the vasculature to identify multifocal disease. In the setting of high clinical suspicion for intracranial mycotic aneurysm with negative imaging results, conventional angiography is reasonable [41].

Findings on CT angiography suggestive of an infected aneurysm include the following [121,123-127] :

● Saccular, eccentric aneurysm or multilobulated aneurysm

● Soft tissue inflammation or mass around a vessel

● Aneurysm with intramural air or air collection around the vessel

● Perivascular fluid collection

In the mesenteric circulation, indistinct fat planes may be indicative of vascular inflammation [128,129]. If a diagnosis of infected aneurysm remains in doubt, a repeat scan can be performed after a short interval to evaluate for rapid enlargement or changes to the aneurysm that suggest infection [124-126].

Nuclear medicine studies, including fluorodeoxyglucose–positron emission tomography (FDG-PET) and gallium scanning, are alternative modalities for evaluating infected aneurysm [130-136]. The use of FDG-PET/CT in the diagnosis of infected aneurysms has been described in case series [71,137].

Imaging studies for detection of extracranial mycotic aneurysm include CT or multislice CT angiography with 3D reconstruction. Transesophageal echocardiography (TEE) is useful for identifying mycotic aneurysm of the sinus of Valsalva and thoracic aorta [41].

Infected versus inflammatory aneurysm — An inflammatory aneurysm is defined as an aneurysm with a ≥1 cm thickness inflammatory rind surrounding the aorta on CT. The periaortic soft tissue density sometimes enhances with intravenous contrast and the ureters may be deviated medially [106]. Periaortic fibrosis associated with inflammatory aneurysm may result in adhesion of adjacent structures, such as the ureters and duodenum to aorta, leading to indistinct retroperitoneal tissue planes on imaging studies. Inflammatory aneurysms are not associated with periaortic air or fluid and are not infected.

There are no randomized trials to guide the management of infected aneurysms. Management strategies are primarily based upon clinical experience guided by case series.

The standard treatment of most infected aneurysms is antibiotic therapy combined with surgical debridement with or without revascularization [118]. Revascularization procedures are performed, as needed, depending upon the affected vascular bed and status of distal perfusion. For patients who refuse surgery or who have significant medical comorbidities that preclude surgical intervention, antibiotic therapy alone is an option.

Antibiotic therapy — The initial choice of antibiotic therapy should be guided by the most likely infecting organism based upon the clinical circumstances. Prior to the availability of culture results, we favor treatment with a combination of vancomycin and an agent with activity against gram-negative organisms, especially Salmonella and enteric gram-negatives; reasonable choices include ceftriaxone, a fluoroquinolone, and piperacillin-tazobactam.

The optimal duration of antibiotic therapy is uncertain and depends on factors, including the immune competence of patient, location of infection, specific bacteria, autogenous versus prosthetic grafts, in situ versus extraanatomic reconstruction, and response to treatment (fever, white count, hemodynamic stability). In general, at least six weeks of parenteral and/or oral antimicrobial therapy is administered for treatment of infected aneurysm. If surgical drainage is performed, this time period commences from the day of surgery.

However, there are no data to support a specific duration of antibiotic therapy; in some circumstances, particularly for cases in which autologous vein grafting is used, a shorter duration may be sufficient. A longer duration of treatment may be warranted in the setting of antibiotic-resistant organisms, persistently positive cultures, and/or inflammatory markers that are slow to normalize [150]. Suppressive oral antibiotics following completion of intravenous therapy may be warranted for patients reconstructed with prosthetic graft material in situ during active infection [8,151,152].

Surgery — Management of infected aneurysms follows the general principles of managing vascular graft infection. The main surgical aim is removal of all necrotic and infected tissue and management of any ensuing ischemia

At present, the use of mycotic has been restricted specifically to fungal infections, but mycotic aneurysm still is used for all extracardiac (or intracardiac) aneurysms of infectious etiology except for syphilitic aortitis.

Endarteritis refers to inflammation of the arterial wall, which may occur with or without coexistent aneurysmal dilation. Unless an aneurysm or coarcta- tion of the aorta is present, infective endarteritis is usually a postmortem diagnosis. Because infected aneurysms differ in their pathogenesis, the various classifications (Table 80.8) are examined separately in the fol- lowing discussion. 817

In a review of more than 22,000 autopsies performed at the Boston City Hospital from 1902 to 1951, 818 aortic aneurysms were found in 1.5%. Mycotic aneurysms constituted only 2.6% of these lesions, however

In another review of 178 aneurysms found among more than 20,000 autopsies at the Mayo Clinic from 1925 to 1954, 819 only 6 were believed to be of infectious origin.

Similarly, in a review 820 of 77 pure iliac artery aneurysms in 48 patients from a 21-year period, only 2 aneurysms (4.2%) were mycotic in origin

With the advent of antibiotics, mycotic aneurysms in IE have become less prevalent and hematogenous seeding of a previ- ously damaged arteriosclerotic vessel constitutes the most common mechanism. In a retrospective review of all emergency department cases seen at one city public hospital from 1994 to 1999, the annual prevalence of arterial mycotic aneurysms among injection drug users was 0.03%. 822

Because most of these lesions arise in areas of severe atherosclerosis, they occur in men more often in a ratio of 3 : 1, and the average age at presentation has been 65 years. The mean age for mycotic aneurysms that occur with IE is younger (approximately 40 years), and men and women are affected approximately equally.

Estimates of the incidence of mycotic aneurysms in patients with IE range up to 15%. 823–826 Two percent to 4% of IE patients develop intracranial mycotic aneurysms, 826,827 although a neurologic presentation is common in patients with IE (noted in 16%–23% of cases), and at least 30% of the patients develop neurologic manifestations. 828,829

These lesions [cerbral mycotic aneurysm] remain a significant cause of morbidity and mortality due to intracerebral and subarachnoid hemorrhage, especially in young people in developing countries, where acute rheumatic fever, rheumatic heart disease, and resultant IE still are prevalent. 830

In addition, aortic root complications, including abscess or mycotic aneurysm, are associated with a poor outcome from IE. In one review, 831 aortic root complications were documented in 23 (46%) of 50 cases of aortic valve IE over a 6-year period; prosthetic valve involvement was common, and the surgical mortality rate and incidence of postop- erative aortic regurgitation were higher in the group with aortic root complications.

Mycotic aneurysms are extremely rare in childhood 832 and when present are usually associated with IE, cardiovascular malformations, or connective tissue disorders.

Pathogenesis Four different mechanisms have been postulated to produce infection of the arterial wall: (1) formation of mycotic aneurysms secondary to septic microemboli to the vasa vasorum (“embolomycotic aneurysms”), 834 (2) extension from a contiguous infected focus, (3) hematogenous seeding of the intima during bacteremia originating from a distant infection, and (4) trauma to the arterial wall with direct contamination. 835

These events, if associated with contamination, usually lead to pseudoaneurysm formation in a peripheral artery and a contiguous abscess in extravasated blood.

The normal arterial intima is very resistant to infection. If this lining is altered by congenital malforma- tions (e.g., coarctation of the aorta) or by acquired disease (especially atherosclerotic plaques or ulcers), resistance to infection is lowered and the surface may become colonized by bloodborne organisms. This hypothesis is analogous to the central role of NBTE in the pathogenesis of IE.

Atherosclerosis accounts for more than 74% of secondarily infected aneurysms. Luetic arteritis and cystic medial necrosis also have been associated with secondary infection. 823

Pathologic Changes Infection of the arterial tree has been recognized by pathologists for more than a century. Virchow first showed local dilation of the arterial wall at the site of a septic embolus in 1847. Infection superimposed on an atherosclerotic aorta first was reported by Koch in 1851. Stengel and Wolfroth 821 collected 217 cases of mycotic aneurysms in 1923. These lesions probably are underreported, and pathologic material has been scant in recent years.

Most mycotic aneurysms that develop during the course of IE are situated in the sinus of Valsalva or in the supravalvular proximal thoracic aorta (>70% develop proximal to the aortic arch)

Aneurysms are more common in the right or posterior sinus and may be complicated by acquired shunts (rupture into the right ventricle is the most common), tamponade, coronary artery occlusion, or an atrioventricular conduction block. 842

Intracranial mycotic aneurysms characteristically develop in the distribution of the middle cerebral artery at peripheral bifurcation points, 829,831 as opposed to a more proximal location for most congenital aneurysms. Multiple intracranial lesions may be present.

Mycotic aneurysm of the extracranial carotid arteries is rare (26 case reports 843 ), but most develop in association with IE, usually due to S. aureus

Multiple lesions are identified in many IE patients with mycotic aneurysms. 834 Saccular forms seem to be more common than fusiform ones. 818 The aneurysms vary in size from 1 mm to more than 10 cm.

The elastica and muscularis layers usually are obliterated, but the intima often is intact. Rupture with surrounding hemorrhage and infection may be present.

Secondary infection of a preexisting aneurysm is found most com- monly in the abdominal aorta (accounting for 70% of the cases), because this is the area most frequently and severely damaged by atherosclerosis.

Even so-called bland aortic aneurysms commonly have some mild inflammation (characterized by a predominance of lymphocytes and mononuclear cells) in the wall; however, infected atherosclerotic aneurysms are characterized by acute inflammation with a predominance of polymorphonuclear leukocytes, necrosis, abscess formation, hemorrhage, and visible bacterial colonies.

Erosion and rupture may be present without aneurysmal dilation. Lumbar or thoracic osteomyelitis is present in one-third of the cases 823 and may precede the aneurysm or develop secondary to contiguous spread from the vascular infection.

When contamination accompanies arterial injury, an infected pseudoaneurysm may result. These lesions are located in the extremities in more than 80% of the cases and are characterized by more extensive local tissue inflammation than is seen with the two types mentioned previously.

Infection as a cause of pseudoaneurysm formation is increas- ing: 17 of 57 (30%) lesions seen in the 1980s 845 were infected. When endarteritis develops after angioplasty, it usually follows a second procedure or repuncture, and this scenario should suggest the diagnosis; all cases have been due to S. aureus. 833,838

Distal emboli, pseudoaneurysm, and coexistent osteomyelitis are present in more than 50% of the cases. Infective aortic root aneurysm also has occurred after coronary artery bypass graft surgery, with disastrous results. 834,846,847 Subclavian artery aneurysms may be present, with systemic findings plus unilateral upper extremity rash or splinter hemorrhages. 848 Nineteen cases of intracavern- ous carotid artery aneurysms have been reported, 849 usually occurring with meningitis with or without IE.