on 12-Feb-2021 (Fri)

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

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].

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

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

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].

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

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].

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

The relationship between these units is defined by the following equations:

mmol/L = [mg/dL x 10] ÷ mol wt

mEq/L = mmol/L x valence

Since the molecular weight of calcium is 40 and the valence is +2, 1 mg/dL is equivalent to 0.25 mmol/L and 0.5 mEq/L. Thus, the normal range of total serum calcium concentration of 8.8 to 10.3 mg/dL is equivalent to 2.2 to 2.6 mmol/L and 4.4 to 5.2 mEq/L

The total serum calcium concentration consists of three fractions [1,2]:

● Approximately 15 percent is bound to multiple organic and inorganic anions such as sulfate, phosphate, lactate, and citrate.

● Approximately 40 percent is bound to proteins, primarily albumin.

● The remaining 45 percent circulates as physiologically active ionized (or free) calcium. The ionized serum calcium concentration is tightly regulated by parathyroid hormone (PTH) and vitamin D, and can be modified by a variety of factors

The wide range in the normal total serum calcium concentration is probably due to variations in the serum concentration of albumin and variations in the state of hydration

Change in total but not ionized calcium — An abnormal total serum calcium concentration in the presence of a normal ionized calcium concentration can occur in patients with hypoalbuminemia, hyperalbuminemia, and multiple myeloma.

Hypoalbuminemia — The total serum calcium concentration will change in parallel to the albumin concentration. Thus, hypoalbuminemia due to hepatic or renal disease is associated with hypocalcemia. By comparison, globulins only minimally bind calcium, and changes in the globulin level are usually not associated with dramatic changes in the calcium concentration, with the occasional exception of marked hyperglobulinemia in multiple myeloma

Traditionally, one of the most widely utilized equations to estimate the total calcium concentration in clinical practice assumes the serum calcium to fall by 0.8 mg/dL (0.2 mmol/L) for every 1.0 g/dL (10 g/L) fall in the serum albumin concentration

Despite widespread use of this formula in clinical practice over the last several decades, more contemporary studies suggest the accuracy of this estimate is quite poor in a variety of populations, including patients hospitalized with critical illness and patients with advanced-stage chronic kidney disease (CKD) [4-10]. The poor performance of calcium-correction formulas in patients with critical illness and CKD may be partially explained by the presence of metabolic acidosis, which can lead to an underestimate of the ionized calcium

Hyperalbuminemia — An elevation in serum albumin, leading to a rise in serum calcium, can be induced by extracellular volume depletion or by fluid movement out of the vascular space due, for example, to a tight tourniquet [11]. Hyperalbuminemia has also been reported in athletes who consume very high-protein diets (more than 2 g of protein per kg of body weight per day)

Multiple myeloma — Myeloma can induce pseudohypercalcemia by a mechanism other than hyperalbuminemia. Rarely, a monoclonal myeloma protein binds calcium with high affinity, potentially leading to a marked elevation in the total serum calcium concentration [13-15]. Since multiple myeloma is commonly associated with true hypercalcemia related to osteolytic lesions, measurement of the ionized calcium can help to differentiate these entities. Likewise, the absence of hypercalcemic symptoms is often a major clue suggesting that the ionized fraction is normal in pseudohypercalcemia and that therapy aimed at correcting the hypercalcemia is not indicated.

The hyperproteinemia in myeloma can also cause a spurious elevation in the serum phosphate concentration [16]. The mechanism involves interference with the molybdate assay commonly used to measure the serum phosphate concentration

Acid-base disorders can lead to changes in the ionized calcium concentration. An elevation in extracellular pH (alkalemia) increases the binding of calcium to albumin, thereby lowering the serum ionized calcium concentration [17]. The fall in ionized calcium with acute respiratory alkalosis is approximately 0.16 mg/dL (0.04 mmol/L or 0.08 mEq/L) for each 0.1 unit increase in pH [17]. Thus, acute respiratory alkalosis, as in the hyperventilation syndrome, can induce symptoms of hypocalcemia, including cramps, paresthesias, tetany, and seizures, although the alkalosis is likely to be of primary importance.

The binding of calcium to albumin that is induced by an elevation in extracellular pH may be important in patients with severe CKD who often have both hypocalcemia and metabolic acidosis, which will tend to raise the ionized calcium concentration. Treatment of the metabolic acidosis with bicarbonate therapy or dialysis can lower the ionized calcium concentration [20,21], which may exacerbate preexisting hypocalcemia and precipitate symptoms such as tetany [21]

Hyperphosphatemia — Acute hyperphosphatemia (as with phosphate release from cells due to a marked increase in cell breakdown) can reduce the ionized serum calcium concentration by binding to circulating calcium. The total serum calcium concentration will also fall in a short period of time as the calcium-phosphate precipitates and is deposited in soft tissues.

In conventional programming languages, there is a clear distinction between types and values. For example, in Haskell, the following are types, representing integers, characters, lists of characters, and lists of any value respectively:

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