**6. The mycotic process in endocarditis**

Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable


Modified from [16].

(cANCA 90%, pANCA 60%) [9]. In most, but not all cases, titres correlated with disease activity. Rising titres should alert the clinician to an increased risk of exacerbation, but are generally

ELISAs are used to specify further the target antigens of ANCA, namely proteinase 3 (PR3; cANCA‐positive samples have a 99% specificity for WG), myeloperoxidase (MPO; 80% specificity for MPA) [6], as well as less important target antigens such as cathepsin G, lacto‐ ferrin, lysozyme and human leucocyte elastase, which are not specific for any particular vasculitic disorder. Whether anti‐bactericidal permeability increasing protein (BPI) ANCA

So, ANCA are not specific for ANCA‐associated vasculitides and despite the high specificity of cANCA/PR3‐ANCA for WG and of MPO‐pANCA for MPA, an increasing number of 'false‐ positive' PR3‐/MPO‐ANCA have been described [10]. More recently, we and others have observed PR3‐ANCA in subacute bacterial endocarditis, a condition sometimes associated with vasculitis [14]. Still, because ANCA test results are usually available before histological analyses are completed, ANCA serology remains the most important tool in the diagnostic repertoire for ANCA‐associated vasculitides, especially in seriously ill patients suspected of having vasculitis. Under life‐threatening conditions, therefore, therapy should be commenced based on clinical and serological findings! An overview of predominant immune phenomena in systemic vasculitides associated with the hypersensitivity reaction types (and the serological

The incidence of ANCA in CSS is much lower than in WG and MPA, and their immunodiag‐ nostic significance is limited [6]. However, active CSS is characterized by increased eosinophils

Furthermore, endothelial cell damage in active AAV is indicated by markedly increased serum thrombomodulin (sTM) values [15]: in CSS, high levels of sTM correlate closely with the soluble interleukin‐2 receptor, which has been shown to be a promising seromarker of disease activity

Because intermittent infections are a major differential diagnostic problem in seriously ill AAV patients (Table 3), a marker that distinguishes between the two conditions is urgently needed. Procalcitonin was recently shown to be normal in active autoimmune rheumatic disorders, but strongly elevated in concomitant bacterial infections and sepsis [17]. However, these findings

Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable

in conjunction with strongly elevated IgE and eosinophil cationic protein values [15].

not regarded as an indication for intensifying therapy [10].

138 Updates in the Diagnosis and Treatment of Vasculitis

markers) is given in Table 2.

have yet to be confirmed [18].

**6. The mycotic process in endocarditis**

in WG [16].

offer further diagnostic perspectives in vasculitis is still unclear [11-13].

**Table 2.** Differential diagnostic features of small vessel vasculitides

congestive heart failure and myocardial abscesses. IE also produces a wide variety of systemic signs and symptoms through several mechanisms, including both sterile and infected emboli and various immunological phenomena [19-21].

IE develops most commonly on the mitral valve, closely followed in descending order of frequency by the aortic valve, the combined mitral and aortic valve, the tricuspid valve, and, rarely, the pulmonic valve. Mechanical prosthetic and bioprosthetic valves exhibit equal rates of infection.

All cases of IE develop from a commonly shared process, as follows:

**1.** Bacteremia (nosocomial or spontaneous) that delivers the organisms to the surface of the valve


GN, glomerulonephritis; Foc. segm. cresc, focal segmental crescentic; nd, not done; s., Streptococcus; n.i., not isolated; cran., cranial; aneurysm., aneurysmatic; neg., negative; nd, not defined.

Reviewed and modified from [39].

**Table 3.** Summary of subacute bacterial endocarditis associated with PR3-ANCA


The common denominator for adherence and invasion is nonbacterial thrombotic endocarditis, a sterile fibrin-platelet vegetation. The development of subacute IE depends on a bacterial inoculum sufficient to allow invasion of the preexistent thrombus. This critical mass is the result of bacterial clumping produced by agglutinating antibodies.

In acute IE, the thrombus may be produced by the invading organism (ie, *S aureus*) or by valvular trauma from intravenous catheters or pacing wires (ie, NIE/HCIE). *S aureus* can invade the endothelial cells (endotheliosis) and increase the expression of adhesion molecules and of procoagulant activity on the cellular surface. Nonbacterial thrombotic endocarditis may result from stress, renal failure, malnutrition, systemic lupus erythematosus, or neoplasia.

The Venturi effect also contributes to the development and location of nonbacterial thrombotic endocarditis. This principle explains why bacteria and the fibrin-platelet thrombus are deposited on the sides of the low-pressure sink that lies just beyond a narrowing or stenosis.

The microorganisms that most commonly produce endocarditis (ie, *S aureus; Streptococcus viridans;* group A, C, and G streptococci; enterococci) resist the bactericidal action of comple‐ ment and possess fibronectin receptors for the surface of the fibrin-platelet thrombus. Among the many other characteristics of IE-producing bacteria demonstrated in vitro and in vivo,

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 141

**•** Increased adherence to aortic valve leaflet disks by enterococci, *S viridans,* and *S aureus*

some features include the following:

CMV, cytomegalovirus.

**Table 4.** Secondary vasculitides

**•** Mucoid-producing strains of *S aureus*

**•** Dextran-producing strains of *S viridans*

**•** *S viridans* and enterococci that possess FimA surface adhesin

In patients with mitral insufficiency, bacteria and the fibrin-platelet thrombus are located on the atrial surface of the valve. In patients with aortic insufficiency, they are located on the ventricular side. In these examples, the atria and ventricles are the low-pressure sinks. In the case of a ventricular septal defect, the low-pressure sink is the right ventricle and the thrombus is found on the right side of the defect.

Nonbacterial thrombotic endocarditis may also form on the endocardium of the right ventricle, opposite the orifice that has been damaged by the jet of blood flowing through the defect (ie, the MacCallum patch).

CMV, cytomegalovirus.

**2.** Adherence of the organisms

140 Updates in the Diagnosis and Treatment of Vasculitis

Reviewed and modified from [39].

**3.** Eventual invasion of the valvular leaflets

cran., cranial; aneurysm., aneurysmatic; neg., negative; nd, not defined.

**Table 3.** Summary of subacute bacterial endocarditis associated with PR3-ANCA

is found on the right side of the defect.

the MacCallum patch).

result of bacterial clumping produced by agglutinating antibodies.

The common denominator for adherence and invasion is nonbacterial thrombotic endocarditis, a sterile fibrin-platelet vegetation. The development of subacute IE depends on a bacterial inoculum sufficient to allow invasion of the preexistent thrombus. This critical mass is the

GN, glomerulonephritis; Foc. segm. cresc, focal segmental crescentic; nd, not done; s., Streptococcus; n.i., not isolated;

In acute IE, the thrombus may be produced by the invading organism (ie, *S aureus*) or by valvular trauma from intravenous catheters or pacing wires (ie, NIE/HCIE). *S aureus* can invade the endothelial cells (endotheliosis) and increase the expression of adhesion molecules and of procoagulant activity on the cellular surface. Nonbacterial thrombotic endocarditis may result from stress, renal failure, malnutrition, systemic lupus erythematosus, or neoplasia.

The Venturi effect also contributes to the development and location of nonbacterial thrombotic endocarditis. This principle explains why bacteria and the fibrin-platelet thrombus are deposited on the sides of the low-pressure sink that lies just beyond a narrowing or stenosis. In patients with mitral insufficiency, bacteria and the fibrin-platelet thrombus are located on the atrial surface of the valve. In patients with aortic insufficiency, they are located on the ventricular side. In these examples, the atria and ventricles are the low-pressure sinks. In the case of a ventricular septal defect, the low-pressure sink is the right ventricle and the thrombus

Nonbacterial thrombotic endocarditis may also form on the endocardium of the right ventricle, opposite the orifice that has been damaged by the jet of blood flowing through the defect (ie,

#### **Table 4.** Secondary vasculitides

The microorganisms that most commonly produce endocarditis (ie, *S aureus; Streptococcus viridans;* group A, C, and G streptococci; enterococci) resist the bactericidal action of comple‐ ment and possess fibronectin receptors for the surface of the fibrin-platelet thrombus. Among the many other characteristics of IE-producing bacteria demonstrated in vitro and in vivo, some features include the following:


**•** Platelet aggregation by *S aureus* and *S viridans* and resistance of *S aureus* to platelet micro‐ bicidal proteins

Colonization of heart valves by microorganisms is a complex process. Most transient bacter‐ emias are short-lived, are without consequence, and are often not preventable. Bacteria rarely adhere to an endocardial nidus before the microorganisms are removed from the circulation

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 143

Once microorganisms do establish themselves on the surface of the vegetation, the process of platelet aggregation and fibrin deposition accelerate at the site. As the bacteria multiply, they are covered by ever-thickening layers of platelets and thrombin, which protect them from neutrophils and other host defenses. Organisms deep in the vegetation hibernate because of the paucity of available nutrients and are therefore less susceptible to bactericidal antimicro‐

Complications of subacute endocarditis result from embolization, slowly progressive valvular destruction, and various immunological mechanisms. The pathological picture of subacute IE is marked by valvular vegetations in which bacteria colonies are present both on and below

The cellular reaction in SBE is primarily that of mononuclear cells and lymphocytes, with few polymorphonuclear cells. The surface of the valve beneath the vegetation shows few organ‐ isms. Proliferation of capillaries and fibroblasts is marked. Areas of healing are scattered among areas of destruction. Over time, the healing process falls behind, and valvular insuffi‐ ciency develops secondary to perforation of the cusps and damage to the chordae tendineae. Compared with acute disease, little extension of the infectious process occurs beyond the

Levels of agglutinating and complement-fixing bactericidal antibodies and cryoglobulins are markedly increased in patients with subacute endocarditis. Many of the extracardiac mani‐ festations of this form of the disease are due to circulating immune complexes. Among these include glomerulonephritis, peripheral manifestations (eg, Osler nodes, Roth spots, subungual hemorrhages), and, possibly, various musculoskeletal abnormalities. Janeway lesions usually

The microscopic appearance of acute bacterial endocarditis differs markedly from that of subacute disease. Vegetations that contain no fibroblasts develop rapidly, with no evidence of repair. Large amounts of both polymorphonuclear leukocytes and organisms are present in an ever-expanding area of necrosis. This process rapidly produces spontaneous rupture of the

The complications of acute bacterial endocarditis result from intracardiac disease and meta‐ static infection produced by suppurative emboli. Because of their shortened course, immuno‐

W illiam Osler first used the term *mycotic aneurysm* in his 1885 Gulstonian Lecture series [23] to refer to an aneurysm resulting from an infectious process of the arterial wall, although a more accurate term might have been *endovascular infection* or *infective vasculitis*, because

leaflets, of the papillary muscles, and of the chordae tendineae.

logical phenomena are not a part of acute IE.

mycotic aneurysms are not due to a fungal organism.

by various host defenses.

the surface.

valvular leaflets.

arise from infected microemboli.

bials that interfere with bacterial cell wall synthesis.

Bacteremia (either spontaneous or due to an invasive procedure) infects the sterile fibrinplatelet vegetation described above. BSIs develop from various extracardiac types of infection, such as pneumonias or pyelonephritis, but most commonly from gingival disease. Of those with high-grade gingivitis, 10% have recurrent transient bacteremias (usually streptococcal species). Most cases of subacute disease are secondary to the bacteremias that develop from the activities of daily living (eg, brushing teeth, bowel movements).

Bacteremia can result from various invasive procedures, ranging from oral surgery to sclero‐ therapy of esophageal varices to genitourinary surgeries to various abdominal operations. The potential for invasive procedures to produce a bacteremia varies greatly. Procedures, rates, and organisms are as follows:


Bacterial adherence to intravascular catheters depends on the response of the host to the presence of this foreign body, the properties of the organism itself, and the position of the catheter. Within a few days of insertion, a sleeve of fibrin and fibronectin is deposited on the catheter. *S aureus* adheres to the fibrin component.

*S aureus* also produces an infection of the endothelial cells (endotheliosis), which is important in producing the continuous bacteremia of *S aureus* BSIs. Endotheliosis may explain many cases of persistent methicillin-susceptible *S aureus* (MSSA) and methicillin-resistant S aureus (MRSA) catheter-related BSIs without an identifiable cause.

*S aureus* catheter-related BSIs occur even after an infected catheter is removed, apparently attributable to specific virulence factors of certain strains of *S aureus* that invade the adjacent endothelial cells. At some point, the staphylococci re-enter the bloodstream, resulting in bacteremia [22].

Four days after placement, the risk of infection markedly increases. Lines positioned in the internal jugular are more prone to infection than those placed in the subclavian vein. Coloni‐ zation of the intracutaneous tract is the most likely source of short-term catheter-related BSIs. Among lines in place for more than 2 weeks, infection of the hub is the major source of bacteremia. In some cases, the infusion itself may be a reservoir of infection.

Colonization of heart valves by microorganisms is a complex process. Most transient bacter‐ emias are short-lived, are without consequence, and are often not preventable. Bacteria rarely adhere to an endocardial nidus before the microorganisms are removed from the circulation by various host defenses.

**•** Platelet aggregation by *S aureus* and *S viridans* and resistance of *S aureus* to platelet micro‐

Bacteremia (either spontaneous or due to an invasive procedure) infects the sterile fibrinplatelet vegetation described above. BSIs develop from various extracardiac types of infection, such as pneumonias or pyelonephritis, but most commonly from gingival disease. Of those with high-grade gingivitis, 10% have recurrent transient bacteremias (usually streptococcal species). Most cases of subacute disease are secondary to the bacteremias that develop from

Bacteremia can result from various invasive procedures, ranging from oral surgery to sclero‐ therapy of esophageal varices to genitourinary surgeries to various abdominal operations. The potential for invasive procedures to produce a bacteremia varies greatly. Procedures, rates,

**•** Endoscopy - Rate of 0-20%; coagulase-negative staphylococci (CoNS), streptococci, diph‐

**•** Barium enema - Rate of 0-20%; enterococci, aerobic and anaerobic gram-negative rods

**•** Transurethral resection of the prostate - Rate of 20-40%; coliforms, enterococci, *S aureus*

**•** Transesophageal echocardiography - Rate of 0-20%; *S viridans,* anaerobic organisms,

Bacterial adherence to intravascular catheters depends on the response of the host to the presence of this foreign body, the properties of the organism itself, and the position of the catheter. Within a few days of insertion, a sleeve of fibrin and fibronectin is deposited on the

*S aureus* also produces an infection of the endothelial cells (endotheliosis), which is important in producing the continuous bacteremia of *S aureus* BSIs. Endotheliosis may explain many cases of persistent methicillin-susceptible *S aureus* (MSSA) and methicillin-resistant S aureus

*S aureus* catheter-related BSIs occur even after an infected catheter is removed, apparently attributable to specific virulence factors of certain strains of *S aureus* that invade the adjacent endothelial cells. At some point, the staphylococci re-enter the bloodstream, resulting in

Four days after placement, the risk of infection markedly increases. Lines positioned in the internal jugular are more prone to infection than those placed in the subclavian vein. Coloni‐ zation of the intracutaneous tract is the most likely source of short-term catheter-related BSIs. Among lines in place for more than 2 weeks, infection of the hub is the major source of

bacteremia. In some cases, the infusion itself may be a reservoir of infection.

the activities of daily living (eg, brushing teeth, bowel movements).

**•** Colonoscopy - Rate of 0-20%; *Escherichia coli, Bacteroides* species

**•** Dental extractions - Rate of 40-100%; *S viridans*

catheter. *S aureus* adheres to the fibrin component.

(MRSA) catheter-related BSIs without an identifiable cause.

bicidal proteins

142 Updates in the Diagnosis and Treatment of Vasculitis

and organisms are as follows:

theroids

streptococci

bacteremia [22].

Once microorganisms do establish themselves on the surface of the vegetation, the process of platelet aggregation and fibrin deposition accelerate at the site. As the bacteria multiply, they are covered by ever-thickening layers of platelets and thrombin, which protect them from neutrophils and other host defenses. Organisms deep in the vegetation hibernate because of the paucity of available nutrients and are therefore less susceptible to bactericidal antimicro‐ bials that interfere with bacterial cell wall synthesis.

Complications of subacute endocarditis result from embolization, slowly progressive valvular destruction, and various immunological mechanisms. The pathological picture of subacute IE is marked by valvular vegetations in which bacteria colonies are present both on and below the surface.

The cellular reaction in SBE is primarily that of mononuclear cells and lymphocytes, with few polymorphonuclear cells. The surface of the valve beneath the vegetation shows few organ‐ isms. Proliferation of capillaries and fibroblasts is marked. Areas of healing are scattered among areas of destruction. Over time, the healing process falls behind, and valvular insuffi‐ ciency develops secondary to perforation of the cusps and damage to the chordae tendineae. Compared with acute disease, little extension of the infectious process occurs beyond the valvular leaflets.

Levels of agglutinating and complement-fixing bactericidal antibodies and cryoglobulins are markedly increased in patients with subacute endocarditis. Many of the extracardiac mani‐ festations of this form of the disease are due to circulating immune complexes. Among these include glomerulonephritis, peripheral manifestations (eg, Osler nodes, Roth spots, subungual hemorrhages), and, possibly, various musculoskeletal abnormalities. Janeway lesions usually arise from infected microemboli.

The microscopic appearance of acute bacterial endocarditis differs markedly from that of subacute disease. Vegetations that contain no fibroblasts develop rapidly, with no evidence of repair. Large amounts of both polymorphonuclear leukocytes and organisms are present in an ever-expanding area of necrosis. This process rapidly produces spontaneous rupture of the leaflets, of the papillary muscles, and of the chordae tendineae.

The complications of acute bacterial endocarditis result from intracardiac disease and meta‐ static infection produced by suppurative emboli. Because of their shortened course, immuno‐ logical phenomena are not a part of acute IE.

W illiam Osler first used the term *mycotic aneurysm* in his 1885 Gulstonian Lecture series [23] to refer to an aneurysm resulting from an infectious process of the arterial wall, although a more accurate term might have been *endovascular infection* or *infective vasculitis*, because mycotic aneurysms are not due to a fungal organism.

Intracranial mycotic aneurysms (ICMAs) complicate about 2% to 3% of infective endocarditis (IE) cases, although as many as 15% to 29% of patients with IE have neurologic symptoms [24-26]. Of all intracerebral aneurysms, only 2% to 6% have an infectious etiology. Signs and symptoms of mycotic aneurysms may be misleading during the early stages, resulting in misdiagnosis and delays in treatment [27]. Early diagnosis of ICMA is the cornerstone of effective treatment.

ICMA in IE. The aim of therapy is to cure the underlying infection and avoid complications from the aneurysm. Some lesions will resolve with antibiotic therapy alone. The decision to pursue surgical management is complex and involves a number of factors, including the number, site, and anatomy of the aneurysm(s) and the comorbidities of the patient. Treatment options for unruptured aneurysms include observation or surgical approaches, such as craniotomy and clipping or endovascular coiling [36,37]. The surgical choice of treatment for ICMA is controversial, patient-specific, and is generally beyond the scope of this article. Fourto 6-week courses of pathogen-specific intravenous antibiotic are recommended. In addition, medical therapy should include control of hypertension and seizures. Therapy should be monitored with serial CTA or MRA, and surgical intervention is generally recommended for enlarging aneurysms in accessible locations. Ruptured aneurysms are treated emergently with

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 145

*Staphylococcus aureus* (~30%), *Salmonella* species (~15%), and less commonly viridans group streptococciaresomeofthecausitiveorganismsofmycoticaneurysmsinthepostantibioticera[38]. Recent reports suggest *Streptococcus pneumoniae*, including penicillin-resistant strains, are reemerging as a cause of mycotic aneurysms [39]. Our patient was infected with *Streptococcus bovis*, a gram-positive cocci classified as group D streptococci. Endocarditis is the most significant clinical infection associated with *S bovis*, but bacteremia from enteric origins also occurs. *S bovis* accounts for 2% to 6% of streptococcal bloodstream isolates from hospitalized patients and for 2.4% to 25% of organisms associated with IE [40-44]. *S bovis* is a rare cause of ICMA, however. Interestingly, *S bovis* endocarditis or bacteremia is associated with concom‐ itant undiagnosed gastrointestinal (GI) tumors in up to 56 % of patients [45]. GI diseases associated with *S bovis* endocarditis include colonic cancers, gastric ulcers, gastric cancer, duodenal ulcers, inflammatory bowel disease, colonic diverticula, angiodysplasia, and liver cirrhosis [40,46-48]. Thus, any patient with *S bovis* bacteremia should undergo screening for occult GI malignancy. Although our patient died before such screening could be completed,

he did have a family history of gastric cancer and a personal history of colon cancer.

Bacterial seeding of vessels may lead to necrosis through direct bacterial action. Vessels may be seeded intraluminally at sites of endothelial injury or flow turbulence. Seeding of vasa vasora may cause destruction of vessels from the outside in. An injury of a large vessel by this

Contiguous spread from an infected site to a vessel may occur. Vessels may also be seeded from within the lumen, as in subacute bacterial endocarditis in which septic emboli embed within the wall of smaller vessels, causing a "mycotic" process via a luminal route. Immune response to bacteria or to bacterial components may also lead to vasculitis, usually by immune-

In subacute bacterial endocarditis, direct spread via septic emboli and immune complex injury

surgery to prevent rebleeding if possible.

**7. Bacterial causes of vasculitis**

complex–mediated mechanisms[24].

may occur.

mechanism is classically termed a "mycotic aneurysm."

Mycotic aneurysms can be divided into 4 types: [1] *embolic*, secondary to bacterial endocarditis (*embolomycotic aneurysms*); [2] *extravascular*, secondary to extension of contiguous infection from a septic focus neighboring an artery; [3] *cryptogenic* or primary bacteremic; and [4] direct contamination following arterial wall trauma, which may be postprocedural [28]. Aneurysms can occur in the cerebral circulation, usually at points of vessel bifurcation, or in the systemic circulation [29].

In IE-associated mycotic aneurysms, septic emboli are released from infected cardiac vegeta‐ tions. These tiny septic emboli occlude the vasa vasorum or entire arterial lumen, which leads to damage to the muscular layer of the vessel. ICMA tend to occur in the more distal portions of the middle cerebral artery, near the surface of the brain, involving the secondary and tertiary branches. In contrast, berry aneurysms occur at proximal branch points in or near the circle of Willis [26]. The outcome depends upon the anatomical location of the embolus, the causative bacteria and associated virulence of the organism, underlying host defenses, and appropriate antibiotic therapy. Mycotic aneurysms can decrease, increase, remain the same in size, or even disappear during treatment for endocarditis [30].

Patients with bacterial intracranial aneurysms have variable neurological symptoms, and early symptoms of infection may be subtle. In ICMA, patients may have symptoms ranging from nonspecific, general complaints, including fever or headache, to neurological deficits or catastrophic intracranial hemorrhage. Laboratory results are typically suggestive of an underlying inflammatory process and may include leukocytosis, elevated erythrocyte sedimentation rate and/or C-reactive protein concentration, and anemia. Blood cultures are almost universally positive for microbial growth.

Computed tomographic angiography, magnetic resonance angiography (MRA), and catheter angiography are used to study the size, location, and morphology of intracranial aneur‐ ysms. Aneurysms 5 mm in diameter or larger can be detected by CTA and MRA. Smaller aneurysms are detected less reliably or detected in retrospect after comparison with cerebral angiography.[31-33]. Cerebral angiography is the gold standard and is often used in preoperative assessment and in determining prognosis[34]; however, it is not routinely recommended due to risk of complications associated with it. The size of the aneurysm during therapy can be safely and accurately monitored using CTA and MRA. In our patient, CTA was selected as the diagnostic tool.

Treatment of ICMA is controversial, in that the appropriate patients for surgical intervention, need for follow-up imaging, and most efficacious treatment are not well delineated in the medical literature. The appropriate treatment always involves medical and sometimes surgical therapies [35]. Moreover, there is no single uniformly accepted approach to the treatment of ICMA in IE. The aim of therapy is to cure the underlying infection and avoid complications from the aneurysm. Some lesions will resolve with antibiotic therapy alone. The decision to pursue surgical management is complex and involves a number of factors, including the number, site, and anatomy of the aneurysm(s) and the comorbidities of the patient. Treatment options for unruptured aneurysms include observation or surgical approaches, such as craniotomy and clipping or endovascular coiling [36,37]. The surgical choice of treatment for ICMA is controversial, patient-specific, and is generally beyond the scope of this article. Fourto 6-week courses of pathogen-specific intravenous antibiotic are recommended. In addition, medical therapy should include control of hypertension and seizures. Therapy should be monitored with serial CTA or MRA, and surgical intervention is generally recommended for enlarging aneurysms in accessible locations. Ruptured aneurysms are treated emergently with surgery to prevent rebleeding if possible.

*Staphylococcus aureus* (~30%), *Salmonella* species (~15%), and less commonly viridans group streptococciaresomeofthecausitiveorganismsofmycoticaneurysmsinthepostantibioticera[38].

Recent reports suggest *Streptococcus pneumoniae*, including penicillin-resistant strains, are reemerging as a cause of mycotic aneurysms [39]. Our patient was infected with *Streptococcus bovis*, a gram-positive cocci classified as group D streptococci. Endocarditis is the most significant clinical infection associated with *S bovis*, but bacteremia from enteric origins also occurs. *S bovis* accounts for 2% to 6% of streptococcal bloodstream isolates from hospitalized patients and for 2.4% to 25% of organisms associated with IE [40-44]. *S bovis* is a rare cause of ICMA, however. Interestingly, *S bovis* endocarditis or bacteremia is associated with concom‐ itant undiagnosed gastrointestinal (GI) tumors in up to 56 % of patients [45]. GI diseases associated with *S bovis* endocarditis include colonic cancers, gastric ulcers, gastric cancer, duodenal ulcers, inflammatory bowel disease, colonic diverticula, angiodysplasia, and liver cirrhosis [40,46-48]. Thus, any patient with *S bovis* bacteremia should undergo screening for occult GI malignancy. Although our patient died before such screening could be completed, he did have a family history of gastric cancer and a personal history of colon cancer.
