Neurologic manifestations
Neurologic complications develop in 25% to 40% of patients with endocarditis, causing major morbidity and increased mor-tality.41-43 Altered mental status at presentation is associated with higher mortality at 6 months.44 Cerebral embolism may be an initial manifestation of endocarditis. Strokes caused by cerebral emboli, commonly to the middle cerebral artery or one of its branches, are the most frequent major neurologic complication, occurring in about 15% of patients. Some patients have multiple small embolic infarcts, which may manifest as an altered level of consciousness, seizures, fluctuating focal neurologic signs, or a combination of these symptoms. An intracerebral hemorrhage in a patient with infective endocarditis can be secondary to an embolic stroke or to rupture of a mycotic aneurysm.42 Cerebral mycotic aneurysms occur in 1% to 5% of patients with infective endocarditis and most commonly affect the distal branches of the middle cerebral arteries.39 Multiple aneurysms occur in some patients. In patients with symptomatic intracranial aneurysms, the overall mortality is high—above 50%. Patients with mycotic aneurysms may present with headache, focal signs, or, if the aneurysm ruptures, manifestations of acute intracerebral or sub-arachnoid hemorrhage. A slowly leaking aneurysm may cause mild meningeal irritation. In such cases, the cerebrospinal fluid, although sterile, may contain erythrocytes, leukocytes, and an increased concentration of protein.
In the search for an intracerebral aneurysm, contrast-enhanced CT may provide localizing information by detecting in-tracerebral bleeding. Magnetic resonance angiography is insufficiently sensitive to reliably detect aneurysms that are 5 mm or less; therefore, cerebral angiography is the optimal diagnostic test.45,46 Cerebral angiography for the detection of aneurysms has been advised for patients with focal neurologic signs, especially in the setting of ABE, and for patients with persistent unexplained headache or meningeal irritation, particularly if anticoagulant therapy is planned.
Treatment of a mycotic aneurysm that has been detected by angiography depends on its location and surgical accessibility, the presence or absence of hemorrhage, and changes in size that may occur during antimicrobial therapy. Resolution or healing of mycotic aneurysms during treatment of endocarditis has been demonstrated by angiography.47 However, a leaking aneurysm, an aneurysm that is large or progressively enlarging, or one that persists after antibiotic therapy should be removed surgically, provided it is accessible. These complex cases should be managed with the input from specialists in infectious disease, neurology, radiology, and neurosurgery.
Brain abscesses are uncommon in SBE. In patients with acute S. aureus endocarditis, septic emboli may give rise to multiple in-tracerebral foci of inflammation or to small abscesses.
Toxic encephalopathy and seizures, which are usually triggered by emboli or strokes, also may complicate active endocarditis. A CSF pleocytosis with polymorphonuclear leukocytes predominating is observed in some patients with ABE caused by pyogenic organisms, especially S. aureus. Patients with SBE may have findings of aseptic inflammation in the CSF.
Endocarditis associated with parenteral drug abuse
The annual incidence of endocarditis in injecting drug users (IDUs) is 0.2% to 2.0%. At the time of their initial attack of endocarditis, 70% to 80% of IDUs have no history or findings of preexisting valvular heart disease. In IDUs, the tricuspid valve is infected more frequently (55%) than the aortic valve (35%) or mitral valve (30%). Multiple episodes of endocarditis are common in IDUs.
S. aureus is responsible for approximately 55% of endocarditis in IDUs [see Table 1].19,48 Although polymicrobial endocarditis, such as simultaneous infection by P. aeruginosa and S. aureus, is extremely rare in non-IDUs with native valve endocarditis, up to 5% of cases in IDUs involve multiple organisms. In IDU-asso-ciated endocarditis, enterococci, streptococci, and Candida primarily infect the aortic and mitral valves. S. aureus and P. aerugi-nosa infect valves on both the right and the left side of the heart. S. aureus, however, accounts for almost 80% of right-sided endocarditis in IDUs. Methicillin-resistant S. aureus (MRSA) is often encountered in these cases, possibly associated with repeated self-administration of antibiotics. Blood cultures generally reveal the causative organism. Microbiologic evaluation of surgically removed arterial emboli may be required to identify the cause in a few cases, such as those caused by fungi.
Although many of the manifestations of endocarditis in IDUs are similar to those of ABE in non-IDUs, there are some differences, because of the high frequency of tricuspid valve involvement, the spectrum of infecting organisms, and occasional pul-monic valve infection. High fevers, chills, rigors, malaise, cough, and, especially, pleuritic chest pain are common presenting complaints in right-sided endocarditis in IDUs. Septic pulmonary emboli occur in about 75% of cases, particularly in patients with S. aureus infection, and cause sputum production, hemoptysis, and initial radiologic findings that may suggest pneumonia. Cavitation of embolic pulmonary lesions is quite common. Significant cardiac murmurs are heard in most patients at some time during their illness but may not be present initially. The murmur of tricuspid regurgitation, a short ejection systolic murmur that is louder on inspiration, may be difficult to detect. Hemodynamically, significant tricuspid insufficiency is manifested by V waves in the jugular vein and a pulsating liver.
Because S. aureus and other pyogenic bacterial species are the predominant causes of infective endocarditis in IDUs, metastat-ic infections are a frequent complication. Neurologic manifestations and peripheral emboli are common; the latter may occlude major vessels and require surgical management.
Prosthetic valve endocarditis
The incidence of PVE is 1% to 2% at 1 year and approximately 0.5% per year thereafter, resulting in a cumulative incidence of 4% to 5% during the first 5 years after valve implantation.49-51 Infection may be introduced at the time of valve placement or from transient bacteremia at any time thereafter. The overall risks of infection are similar for mechanical and porcine biopros-thetic valves and for aortic and mitral valve prostheses.49-51 The leading cause of PVE during the first year after surgery is methi-cillin-resistant coagulase-negative staphylococci, predominantly S. epidermidis [see Table 2]. Coagulase-negative staphylococci continue to cause cases of PVE that occur a year or more after surgery; however, these staphylococci are often species other than S. epidermidis, and only 20% to 30% are methicillin resistant. S. aureus, streptococci, enterococci, and fastidious gram-negative coccobacilli, the leading organisms associated with native valve endocarditis, cause about three quarters of PVE cases after 1 year following valve replacement.49-51 Coagulase-negative staphylo-cocci are responsible for at least 35% of cases of PVE and, therefore, should not be dismissed as contaminants (which they usually are in other settings) if isolated from the blood of a patient who has a prosthetic valve.
Infection of prosthetic valves is often associated with invasion of perivalvular tissues—resulting in valve-ring abscessses and valvular dysfunction—and occasionally with myocardial ab-scesses.41,49,52,53 Necrosis of the annulus from invasive infection can cause partial dehiscence of the prosthesis, resulting in hemo-dynamically significant paravalvular regurgitation. These pathologic changes can occur with either porcine or mechanical prostheses, particularly when the valves are in the aortic position or when infection occurs during the first postoperative year.51,54 Occasionally, vegetations may partially obstruct the valve orifice or restrict valve movement, causing functional stenosis. Such changes are more likely with prostheses in the mitral position. When infection is restricted to the leaflets of a porcine bioprosthetic valve, leaflet destruction, obstructing vegetations, and the delayed onset of leaflet stiffness may cause clinically significant valvular dysfunction.54
Table 2 Etiology of Prosthetic Valve Endocarditis4990110111
|
Organism |
Time of Onset after Valve Implantation and Percentage of Cases |
||
|
< 2 Months |
2-12 Months |
> 12 Months |
|
|
Coagulase-negative staphylococci |
54 |
56 |
15 |
|
Staphylococcus aureus |
8 |
9 |
13 |
|
Gram-negative bacilli |
12 |
3 |
1 |
|
Streptococci |
rare |
3 |
34 |
|
Enterococci |
rare |
6 |
11 |
|
Corynebacteria |
8 |
rare |
1 |
|
HACEK |
rare |
3 |
14 |
|
Fungi |
6 |
6 |
3 |
|
Miscellaneous |
6 |
6 |
1 |
|
Culture-negative |
5 |
9 |
5 |
The dominant clinical feature of PVE that occurs during the first 60 days after surgery (early PVE) is fever, whether or not there is a regurgitant murmur associated with the prosthetic valve. Prosthetic valve dysfunction with resulting heart failure is seen in some patients. Petechiae occur in about half of patients with early PVE, but Roth spots, Osler nodes, and Janeway lesions are not common. Emboli are common in early PVE; emboli that occlude large peripheral arteries suggest fungal endocarditis. Because blood cultures are often negative in patients with fungal endocarditis, this diagnosis must often be made on the basis of histologic examination, culture, and sometimes molecular testing of surgical or autopsy specimens or vegetation recovered at embolectomy.
The clinical features of PVE that occurs more than 60 days after surgery (late PVE) are similar to those of acute or subacute endocarditis on native valves, depending on the infecting organism.
Diagnosis
Duke criteria
Although the diagnosis of endocarditis may be readily evident in patients with the classic syndrome of fever, a murmur associated with valvular dysfunction, typical peripheral signs, and bacteremia, the diagnosis is less evident in most patients.55 A diagnostic approach known as the Duke criteria has been designed by the Duke Endocarditis Service56 [see Tables 3 and 4]. With these criteria, the diagnosis of endocarditis can be established definitively by either pathologic or clinical criteria. The pathologic criteria include direct evidence gleaned from surgery or autopsy, and the clinical criteria are derived from microbio-logic data (culture, serologic or molecular testing), echocardiog-raphy, physical examination, and other laboratory findings [see Table 4]. In retrospective evaluations of pathologically proven cases of native valve endocarditis and PVE, these clinical criteria have been found to be both sensitive56-58 and highly specific.57,59,60 Misdiagnoses rarely resulted when these clinical criteria were used to reassess previously pathologically confirmed cases. The specificity and negative predictive values of these criteria have been reported as 99% and 92%, respectively.59,60 Use of these clinical criteria very rarely results in the rejection of cases considered to be endocarditis on independent expert evaluation.61
|
Table 3 Duke Criteria for the Diagnosis of Infective Endocarditis52,72,112,113 |
|
Definite |
|
Pathologic criteria |
|
1. Microorganisms: demonstrated by culture, Gram stain, histologically, or by a validated molecular test in a vegetation, in a vegetation that has embolized, or in an intracardiac abscess specimen |
|
or 2. Pathologic lesions: vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis |
|
Clinical criteria* |
|
1. Two major criteria |
|
or 2. One major and three minor criteria |
|
or 3. Five minor criteria |
|
Possible |
|
Findings consistent with infective endocarditis that fall short of "definite" but are not "rejected" |
|
Rejected |
|
1. Firm alternative diagnosis for manifestations of infective endocarditis or |
|
2. Resolution of endocarditis syndrome with antibiotic therapy for < 4 days or |
|
3. No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for < 4 days |
|
Table 4 Definitions of Terms Used in Duke Criteria for the Diagnosis of Infective Endocarditis56 |
|
Major criteria |
|
1. Positive blood cultures for the following: Typical microorganism consistent with diagnosis from two separate blood cultures a. Viridans streptococci, Streptococcus bovis, or HACEK organisms |
|
or b. Community-acquired Staphylococcus aureus or enterococ-ci, in the absence of a primary focus |
|
Persistently positive blood cultures, defined as microorganisms consistent with diagnosis from the following: a. At least two blood samples drawn > 12 hr apart |
|
b. Three of three or a majority when more than three blood cultures are drawn, with first and last samples drawn at least 1 hr apart |
|
2. Evidence of endocardial involvement Positive echocardiogram for IE a. Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material, in the absence of an alternative anatomic explanation |
|
b. Abscess or |
|
c. New partial dehiscence of prosthetic valve |
|
New valvular regurgitation (changing of preexisting murmur not sufficient) |
|
Minor criteria |
|
1. Predisposition: predisposing heart condition or I.V. drug use |
|
2. Fever: temperature > 38° C (100.4° F) |
|
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions |
|
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor |
|
5. Microbiologic evidence: positive blood culture but not meeting a major criterion (see above)* or serologic evidence of active infection with organism consistent with IE |
|
6. Echocardiogram consistent with infective endocarditis but not meeting a major criterion (see above) |
*Excludes single positive cultures for coagulase-negative staphylococci, diphtheroids, and organisms that do not commonly cause endocarditis. IE—infective endocarditis
Echocardiography
The Duke criteria utilize echocardiography for defining the anatomic features of endocarditis. Both the sensitivity and specificity of echocardiography are high when experienced echocar-diographers apply specific criteria. In patients with pathologically proven native valve endocarditis, vegetations can be detected in 60% to 75% by use of transthoracic echocardiography (TTE) and in 87% to 94% with transesophageal echocardiogra-phy (TEE); the specificity of both techniques is high.62-64 TEE is notably superior to TTE in the evaluation of patients with suspected PVE65 [see Prosthetic Valve Endocarditis, above]. Notwithstanding the increased sensitivity of TEE compared with TTE, if the decision is made to treat all cases identified by the Duke criteria as definite endocarditis and most cases identified as possible endocarditis, then evaluation by TEE rarely alters the treatment decision. Occasional exceptions to this observation are PVE cases that were missed by TTE. Echocardiography is the preferred technique for identification of perivalvular infection and other intracardiac complications of endocarditis. For detection of abscesses, a transesophageal study is significantly more sensitive (76% to 87%) than transthoracic imaging (18% to 28%), with equal specificity.53,65,66
All patients in whom endocarditis is seriously suspected should undergo echocardiography. However, echocardiogra-phy should not be regarded as a general screening test for patients with a low prior probability of endocarditis (e.g., most patients with acute febrile illnesses). Given its high sensitivity, a negative transesophageal echocardiogram is good evidence against endocarditis in patients at low or intermediate risk of this infection. Conversely, if the prior probability of endocarditis is high, a negative echocardiogram does not fully exclude the diagnosis; the false negative rate for transesophageal echocardiog-raphy is 6% to 13%.67 A repeat transesophageal study in patients with endocarditis reduces the false negative results to approximately 5%.67 Finally, echocardiography cannot reliably distinguish an infected vegetation from a sterilized vegetation, non-bacterial thrombotic vegetations of marantic endocarditis, or in-tracardiac thrombi, as seen in the antiphospholipid antibody syndrome.
Transthoracic echocardiography has limited usefulness in the diagnosis of PVE because the prosthesis itself produces echoes that often obscure vegetations and abscesses. Transesophageal two-dimensional and Doppler echocardiography more effectively assess prosthetic valves and perivalvular tissues, especially when a mitral valve prosthesis is present.68,69 In PVE, the trans-esophageal technique identified vegetations in 82% of patients, compared with a 36% identification rate with transthoracic echocardiography.53 Similarly, detection of paravalvular abscesses in patients with PVE is markedly increased by use of transesophageal rather than transthoracic echocardiography.
