INTRODUCTION — Infective endocarditis (IE) refers to infection of the endocardial surface of the heart; it usually refers to infection of one or more heart valves or infection of an intracardiac device.
The clinical manifestations and evaluation of adults with suspected left-sided native valve IE will be reviewed here. Issues related to right-sided native valve IE are discussed separately. (See "Right-sided native valve infective endocarditis".)
Issues related to risk factors, complications, antimicrobial therapy, surgery, and outcome of native valve IE are discussed separately:
●(See "Native valve endocarditis: Epidemiology, risk factors, and microbiology".)
●(See "Complications and outcome of infective endocarditis".)
●(See "Antimicrobial therapy of left-sided native valve endocarditis".)
●(See "Surgery for left-sided native valve infective endocarditis".)
Issues related to clinical manifestations, diagnosis, and management of prosthetic valve IE and cardiac device infections are also discussed separately:
●(See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)
●(See "Antimicrobial therapy of prosthetic valve endocarditis".)
●(See "Surgery for prosthetic valve endocarditis".)
RISK FACTORS — Risk factors for native valve infective endocarditis (IE) include cardiac factors (history of prior IE or pre-existing valvular or congenital heart disease), underlying conditions (such as intravenous drug use, an indwelling cardiac device or intravenous catheter, or immunosuppression), or a recent dental or surgical procedure. Issues related to risk factors for IE are discussed further separately. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology", section on 'Risk factors'.)
CLINICAL MANIFESTATIONS — The clinical manifestations of infective endocarditis (IE) are variable; IE may present as an acute, rapidly progressive infection or as a subacute or chronic disease with low-grade fever and nonspecific symptoms [1,2].
Symptoms and signs — Fever is the most common symptom of IE (up to 90 percent of patients); it is often associated with chills, anorexia, and weight loss. Fever patterns in IE vary widely; their temporal patterns or severity have no diagnostic utility. Patients with IE typically have continuous bacteremia, regardless of whether fever is present. Other common symptoms of IE include malaise, headache, myalgias, arthralgias, night sweats, abdominal pain, and dyspnea [3]. Patients with IE associated with dental infection may report tooth pain or related symptoms.
Cardiac murmurs are observed in approximately 85 percent of patients. Supportive signs include splenomegaly and cutaneous manifestations such as petechiae or splinter hemorrhages. Petechiae are observed in 20 to 40 percent of patients; they may be present on the skin (usually on the extremities) or on mucous membranes such as the palate or conjunctivae (picture 1). Splinter hemorrhages consist of nonblanching linear reddish-brown lesions under the nail bed (picture 2). However, neither their presence nor location are diagnostic of IE, as they are commonly found in otherwise normal patients [4]. (See "Auscultation of cardiac murmurs in adults".)
Clinical manifestations reflecting complications of IE may be present at the time of initial presentation and/or may develop subsequently, as discussed below. When present, such findings warrant independent diagnostic evaluation, concurrent with evaluation for IE. (See 'Complications as presenting symptoms' below.)
Relatively uncommon clinical manifestations that are highly suggestive of IE include:
●Janeway lesions – Nontender erythematous macules on the palms and soles (picture 3)
●Osler nodes – Tender subcutaneous violaceous nodules mostly on the pads of the fingers and toes, which may also occur on the thenar and hypothenar eminences (picture 4)
●Roth spots – Exudative, edematous hemorrhagic lesions of the retina with pale centers
Janeway lesions are more common in acute than subacute IE; histologically, they reflect microabscesses with neutrophil infiltration of capillaries. Osler nodes and Roth spots occur most frequently in the setting of a protracted time course of endocarditis; they probably represent the sequelae of vascular occlusion by microthrombi leading to localized immune-mediated vasculitis. Roth spots (also described as Litten spots) occur in 2 percent of patients with IE [5]. Osler nodes were commonly observed among patients with IE in the preantibiotic era, but are now uncommon since IE is frequently diagnosed and treated before their development.
Complications as presenting symptoms — IE is associated with a broad array of systemic complications due to septic embolization, which may be associated with localized thrombosis, bleeding, infection, and/or development of immune reactions. Clinical manifestations reflecting these complications may be present at the time of initial presentation and/or may develop subsequently (see "Complications and outcome of infective endocarditis"):
●Cardiac complications (up to 50 percent of patients) – Valve regurgitation, heart failure, and others. In patients with a new diagnosis of valve regurgitation, and in patients with mitral valve prolapse and a new diagnosis of chordal rupture, IE warrants consideration even in the absence of fever.
●Neurologic complications (up to 40 percent of patients) – Embolic stroke, intracerebral hemorrhage, brain abscess, and others.
●Septic emboli (up to 25 percent of patients) – Infarction of kidneys, spleen, and other organs. In patients with concomitant right-sided endocarditis, septic pulmonary emboli may be seen (image 1). (See "Right-sided native valve infective endocarditis".)
●Metastatic infection (such as vertebral osteomyelitis, septic arthritis, splenic or psoas abscess).
●Systemic immune reaction (eg, glomerulonephritis).
Detection of the full spectrum of clinical manifestations of IE complications requires a careful, focused initial evaluation as well as serial follow-up examinations. As examples, patients with IE may present with clinical manifestations of congestive heart failure due to valvular regurgitation, focal neurologic complaints due to an embolic stroke, or back pain due to vertebral osteomyelitis. A thorough investigation of extracardiac manifestations is particularly important in the setting of Staphylococcus aureus bacteremia given the virulence of this organism. Issues related to complications of IE are discussed further separately. (See "Clinical manifestations of Staphylococcus aureus infection in adults" and "Complications and outcome of infective endocarditis".)
Laboratory findings — Routine laboratory findings in the setting of IE are relatively nonspecific; they may include elevated inflammatory markers (erythrocyte sedimentation rate and/or elevated C-reactive protein), normochromic-normocytic anemia, and positive rheumatoid factor. Hyperglobulinemia, cryoglobulinemia, circulating immune complexes, hypocomplementemia, and false-positive serologic tests for syphilis occur in some patients. Urinalysis may demonstrate microscopic hematuria, proteinuria, and/or pyuria. The presence of red blood cell casts on urinalysis is generally indicative of glomerulonephritis, which is a minor diagnostic criterion for IE. (See 'Diagnostic (modified Duke) criteria' below.)
Electrocardiography may demonstrate new or evolving conduction disease (first- or second-degree atrioventricular block, bundle branch block, or complete heart block), reflecting paravalvular or myocardial extension of infection [6].
In patients with known congenital or valvular heart disease who are being followed with serial echocardiography, endocarditis may be initially suspected based on new echocardiographic findings, particularly new or worsening valve regurgitation or a new intracardiac shunt. In such cases, blood cultures should be obtained. (See 'Blood cultures' below.)
DIAGNOSIS
Overview of diagnostic approach
●When to suspect IE − The diagnosis of infective endocarditis (IE) should be suspected in patients with bacteremia due to an organism with known propensity to cause endocarditis; other important clues include fever, relevant cardiac risk factors (prior IE, history of valvular or congenital heart disease), and other predisposing conditions (intravenous drug use, indwelling cardiac device or intravenous catheter, immunosuppression, or a recent dental or surgical procedure).
●Establishing a diagnosis of IE − The diagnosis is established based on clinical manifestations, blood cultures (or other microbiologic data), and cardiac imaging [3]. The diagnosis of IE requires (1) identification of the infecting pathogen by blood culture, serologic testing, or molecular testing and (2) cardiac imaging to identify a valvular vegetation, paravalvular abscess, or other structural complication of infection. The accepted criteria for diagnosis of IE are the modified Duke criteria, which are summarized below and in the tables (table 1 and table 2) (calculator 1).
•Blood cultures − At least three sets of blood cultures should be obtained from separate venipuncture sites prior to initiation of antibiotic therapy. For patients who are clinically stable, antimicrobial therapy may be deferred while awaiting the results of blood cultures and other diagnostic tests. For patients with signs of clinical instability, initiation of empiric antimicrobial therapy (after blood cultures have been obtained) is appropriate. Follow-up blood cultures should be obtained 48 to 72 hours after antimicrobial therapy is begun and repeated every 48 to 72 hours until clearance of bacteremia is documented. (See 'Blood cultures' below and "Detection of bacteremia: Blood cultures and other diagnostic tests" and "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Empiric therapy'.)
•Cardiac imaging − Echocardiography remains the standard imaging modality for evaluation of cardiac valves; fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) has emerged as an adjunctive imaging modality.
Echocardiography should be performed in all patients with suspected IE (table 1 and table 2 and algorithm 1 and algorithm 2) [1,7-9]. In general, transthoracic echocardiography (TTE) is the first diagnostic test for patients with suspected IE. Transesophageal echocardiography (TEE) has higher sensitivity than TTE and is better for detection of cardiac complications such as abscess, leaflet perforation, and pseudoaneurysm. TEE should be performed in patients in whom there is suspicion for IE and the TTE is nondiagnostic. In some circumstances, it is reasonable to forgo TTE and proceed directly to TEE. (See 'Echocardiography' below.)
FDG PET/CT has emerged as a diagnostic tool for IE, which can identify infection of native valves and paravalvular areas, as well as extracardiac sites of infection. The sensitivity of FDG PET/CT for diagnosis of native valve IE is lower than for prosthetic valve IE; this is likely due to fibrosis in native valve IE, compared with inflammation in prosthetic valve IE [10].
Cardiac CT imaging can be used for detection of paravalvular abscess when TEE is nondiagnostic and an abscess is suspected [11-13].
•Additional evaluation − Additional evaluation for patients with suspected IE includes electrocardiography, chest radiography, other radiographic imaging tailored to clinical manifestations, and dental evaluation.
-Electrocardiography – Baseline electrocardiography should be performed as part of the initial evaluation for all patients with suspected IE, with subsequent telemetry monitoring or serial electrocardiograms. The presence of heart block or conduction delay (which may manifest initially as a prolonged PR interval) may provide an important clue to paravalvular extension of infection to the valve annulus and adjacent septum (which should prompt further evaluation with echocardiography as discussed below). In addition, the presence of findings consistent with ischemia or infarction may suggest the presence of emboli to the coronary circulation. (See "ECG tutorial: Basic principles of ECG analysis" and 'Echocardiography' below.)
-Chest radiography – Chest radiography is warranted to evaluate for presence of septic pulmonary emboli (image 1), infiltrate (with or without cavitation), congestive heart failure, and potential alternative causes of fever and systemic symptoms.
-Computed tomography (CT) – CT of the torso (chest, abdomen, and pelvis) is useful to evaluate for sites of metastatic infection (such as splenic infarct, renal infarcts, psoas abscess, or other sites of infection) that may warrant localized drainage [1,14]. However, the decision to pursue this imaging should be guided by a careful history and clinical assessment. In one study including more than 500 patients with possible or definite IE who underwent thoracoabdominal CT, the diagnosis of IE was upgraded from possible to definite in only 0.8 percent of cases; acute kidney injury within five days of imaging was observed in 15 percent of patients [15].
-Additional radiographic imaging − Additional radiographic imaging to evaluate for complications of IE should be tailored to findings on history and physical examination [1]. As examples, patients with back pain should be evaluated for the possibility of vertebral osteomyelitis with imaging studies (see "Vertebral osteomyelitis and discitis in adults"), and patients with headache, neurologic deficits, or meningeal signs should be evaluated with head magnetic resonance imaging (MRI) for neurologic complications (including intracranial mycotic aneurysm or central nervous system bleeding). (See "Overview of infected (mycotic) arterial aneurysm".)
Routine brain imaging with CT or MRI is not necessary in the absence of focal neurologic signs or symptoms. However, as asymptomatic cerebral infarcts are quite common in patients with IE; the presence of such lesions can be diagnostically important if they are detected in patients with other clinical findings suggestive of IE [1,16-18]. For example, in one study including 53 patients, early use of cerebral MRI led to upgraded classification of IE to definite or possible in one-third of cases [16]. In a systematic review and meta-analysis including 21 studies (mostly retrospective) among more than 2100 patients with suspected or confirmed IE who underwent brain MRI, acute ischemic lesions or microbleeds were observed in more than half of cases; hemorrhagic lesions, abscess, meningitis, and intracranial mycotic aneurysms were observed less commonly [19].
-Dental evaluation − Patients with streptococcal IE should undergo a thorough dental evaluation; the examination should focus on periodontal inflammation, pocketing around teeth, and caries that may result in pulpal infection and subsequent abscess [1]. All active sources of oral infection should be eradicated, and patients should be counseled regarding the importance of daily dental hygiene with serial dental evaluation. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Follow up'.)
Diagnostic (modified Duke) criteria — The modified Duke criteria stratify patients into the following categories: definite IE, possible IE, and rejected IE (table 1) based on pathologic and clinical criteria (table 2) [20]. The Duke criteria should be used as a diagnostic guide together with clinical judgment and must be interpreted in view of the pretest probability for IE. The criteria were developed for evaluation of patients with left-sided native valve IE; their sensitivity is diminished in patients with suspected prosthetic valve IE, right-sided IE, and cardiac device infection [21].
Since the initial development of the Duke criteria, changes in epidemiology, clinical presentation, and diagnostic tools warrant further consideration in the context of clinical practice.
As an example, enterococcal bacteremia is included as a major Duke criterion if it is community associated and in the absence of a primary focus (table 2). However, in a prospective study including 344 patients with E. faecalis bacteremia evaluated with echocardiography, consideration of E. faecalis as a "typical" endocarditis pathogen (regardless of the place of acquisition or the portal of entry) improved the sensitivity for identification of definite endocarditis from 70 to 96 percent [22]. This study suggests that even if there is a known health care-acquired extra-cardiac source of infection in a patient with E. faecalis bacteremia, the potential for IE should not be dismissed.
Definite IE is established in the presence of any of the following (table 1):
●Pathologic criteria:
•Pathologic lesions – Vegetation or intracardiac abscess demonstrating active endocarditis on histology
•Microorganisms – Demonstrated by culture or histology of a vegetation or intracardiac abscess
●Clinical criteria:
•Two major clinical criteria
•One major and three minor clinical criteria
•Five minor clinical criteria
Possible IE is defined as the presence of one major and one minor clinical criteria or the presence of three minor clinical criteria (table 1).
The diagnosis of IE may be rejected if any of the following are present (table 1):
●A firm alternate diagnosis is made.
●Resolution of clinical manifestations occurs after ≤4 days of antibiotic therapy.
●No pathological evidence of infective endocarditis is found at surgery or autopsy after antibiotic therapy for four days or less.
●Clinical criteria for possible or definite infective endocarditis is not met.
Clinical criteria (major and minor) for the diagnosis of IE are summarized in the table (table 2).
Major clinical criteria include (table 2):
●Positive blood cultures (one of the following):
•Typical microorganisms consistent with IE from two separate blood cultures (Staphylococcus aureus, viridans streptococci, Streptococcus gallolyticus [formerly S. bovis], HACEK [Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella] group, or community-acquired enterococci in the absence of a primary focus) OR
•Persistently positive blood cultures
-For organisms that are typical causes of endocarditis: At least two positive blood cultures from blood samples drawn >12 hours apart
-For organisms that are more commonly skin contaminants: Three or a majority of ≥4 separate blood cultures (with first and last drawn at least one hour apart), OR
•Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer >1:800 [23]
●Evidence of endocardial involvement (one of the following):
•Echocardiography positive for IE
-Vegetation (oscillating intracardiac mass on a valve or on supporting structures, in the path of regurgitant jets, or on implanted material, in the absence of an alternative anatomic explanation), OR
-Abscess, OR
-New partial dehiscence of prosthetic valve
•New valvular regurgitation
Minor clinical criteria include (table 2):
●Predisposition – Intravenous drug use or presence of a predisposing heart condition (prosthetic heart valve or a valve lesion associated with significant regurgitation or turbulence of blood flow)
●Fever – Temperature ≥38.0°C (100.4°F)
●Vascular phenomena – Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, or Janeway lesions
●Immunologic phenomena – Glomerulonephritis, Osler nodes, Roth spots, or rheumatoid factor
●Microbiologic evidence – Positive blood cultures that do not meet major criteria OR serologic evidence of active infection with organism consistent with IE
The Duke criteria have been validated in multiple studies [20,24-27]. In one study including 69 pathologically proven cases IE, 80 percent were classified as definite IE using the Duke criteria [20]. In another study including 54 surgical and autopsy-proven cases of IE, none were rejected by the Duke criteria [26].
Diagnostic tools — Diagnostic tools for IE include microbiologic data (usually blood cultures) and echocardiography.
Microbiology cultures
Blood cultures
Collection and interpretation — Positive blood culture is the cornerstone of microbiological diagnosis of IE; three sets of blood cultures detect 96 to 98 percent of bacteremia [3]. At least three blood culture sets (a set consists of one aerobic bottle and anaerobic bottle) should be obtained prior to initiation of antibiotic therapy; each blood culture set should be obtained from a separate venipuncture site [28,29]. Patients with IE typically have continuous bacteremia; therefore, blood cultures may be collected at any time and need not necessarily be obtained at the time of fever or chills [30]. Blood culture results should be interpreted based on the modified Duke criteria, as summarized above. (See 'Diagnostic (modified Duke) criteria' above and "Detection of bacteremia: Blood cultures and other diagnostic tests".)
The diagnostic yield of more than three sets of blood cultures is minimal in the absence of recent antimicrobial therapy. In one series including 206 cases of IE, the initial blood culture in patients with streptococcal endocarditis was positive in 96 percent of cases, and one of the first two blood cultures was positive in 98 percent [31]. In patients with IE caused by organisms other than Streptococcus, the first blood culture was positive in 82 percent of cases, and one of the first two cultures was positive in 100 percent of cases [31].
Most clinically significant bacteremias are detected within 48 hours; common and fastidious pathogens (such as members of the HACEK group) are usually detected within five days of incubation with modern automated blood culture detection systems. The volume of blood for each blood culture set in adults is 20 mL (10 mL into each bottle). Additional issues related to blood cultures for detection of bacteremia are discussed further separately. (See "Detection of bacteremia: Blood cultures and other diagnostic tests".)
In patients who have received recent antimicrobial therapy, additional blood cultures may be useful (two to three sets over several days). The utility of repeat blood cultures depends on the underlying clinical circumstances. For example, many patients with S. aureus IE have positive blood cultures for several days after initiation of antimicrobial therapy, whereas patients with IE due to highly susceptible strains of bacteria such as viridans group streptococci may have negative blood cultures after a few doses of antimicrobial therapy.
Typical microorganisms consistent with IE include S. aureus, viridans streptococci, S. gallolyticus (formerly S. bovis), HACEK organisms, or enterococci. The likelihood of IE is greater in the setting of bacteremia due to Streptococcus sanguis than Streptococcus milleri [32]. Bacteremia due to group G Streptococcus is more frequently associated with IE than bacteremia due to group A or C streptococci [33]. Bacteremia due to Enterococcus faecalis has been more frequently associated with IE than bacteremia due to other enterococcal species [34]. The microbiology of IE is discussed further separately. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology", section on 'Microbiology' and "Infections due to the Streptococcus anginosus (Streptococcus milleri) group" and "Group C and group G streptococcal infection".)
False-positive culture results occasionally occur. Organisms for which it can be difficult to distinguish between pathogenicity and contamination include Cutibacterium (formerly Propionibacterium) acnes, Corynebacterium species, Bacillus species, and coagulase-negative staphylococci. In general, the likelihood of pathogenicity is increased if the organism is observed in multiple blood cultures obtained by independent venipunctures. Recovery of these organisms from a single blood culture or a minority of blood culture bottles likely reflects a false-positive result. (See "Detection of bacteremia: Blood cultures and other diagnostic tests", section on 'Assessing clinical significance'.)
Culture-negative endocarditis — Culture-negative IE is defined as endocarditis with no definitive microbiologic etiology following inoculation of at least three independently obtained blood samples in a standard blood-culture system, with negative cultures after five days of incubation and subculturing.
There are three main categories of culture-negative IE: IE due to bacterial pathogens whose growth in culture is prevented by antecedent antimicrobial therapy, IE due to microorganisms with fastidious growth characteristics in vitro (such as Gemella, Granulicatatella, and Abiotrophia species), and IE due to intracellular bacteria that cannot be cultured from blood using standard microbiologic testing methods [35].
Culture-negative IE should be suspected in patients with negative blood cultures and persistent fever with one or more clinical findings consistent with IE (eg, stroke or other manifestations of emboli). Culture-negative IE should also be suspected in patients with vegetation on echocardiogram and no clear microbiologic diagnosis. Some causes of culture-negative IE may be identified via serology or polymerase chain reaction (PCR); these include Coxiella burnetii, Bartonella spp, Chlamydia spp, Legionella spp, Mycoplasma, and Brucella [23].
Valve culture and histopathology — The diagnosis of IE may be established via pathologic criteria, including presence of microorganisms (demonstrated by culture or histology of a vegetation or intracardiac abscess), or histology (vegetation or intracardiac abscess demonstrating active endocarditis) (table 1). Culture of resected heart valves may be useful for cases in which blood cultures have been negative, but routine valve culture is not warranted in the absence of clinical suspicion for IE because it may be associated with false-positive findings. In one study including 1030 valves removed at surgery, cultures were positive in 39 percent of patients that met Duke criteria for IE and in 28 percent of patients without other criteria for IE [36].
Cardiac imaging — Echocardiography is the mainstay of cardiac imaging for diagnosis of IE. Additional cardiac tools may be useful in some circumstances (where available), as discussed below.
Echocardiography — Echocardiography should be performed in all patients with suspected IE as soon as possible after the diagnosis of IE is suspected; false-negative results may be obtained if vegetations are small and/or if vegetations have embolized (table 1 and table 2 and algorithm 1 and algorithm 2) [1,7,9,37]. Echocardiography is warranted even for patients with an associated condition that requires a protracted course of antimicrobial therapy (such as vertebral osteomyelitis), since documenting the presence or absence of vegetation is important for determination of subsequent follow-up. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Follow up'.)
Echocardiography is considered positive for IE in the setting of vegetation, abscess, or new dehiscence of a prosthetic valve (movie 1 and movie 2 and movie 3 and movie 4). Echocardiography is also useful for evaluating valvular dysfunction, assessing hemodynamic severity of the valve lesion, assessing underlying ventricular function, and detecting associated abnormalities such as shunts. In addition, echocardiography is an important tool for follow-up evaluation of patients with persistent or recurrent bacteremia or other clinical deterioration. (See 'Diagnostic (modified Duke) criteria' above and "Role of echocardiography in infective endocarditis".)
In general, TTE is the first diagnostic test for patients with suspected IE. The sensitivity is modest (up to 75 percent); the specificity approaches 100 percent [38]. Thus, the absence of vegetation on TTE does not preclude the diagnosis of IE, although the presence of normal valve morphology and function on TTE substantially reduces the likelihood of IE [39]. In one study including 134 patients with suspected IE, 96 percent of patients with normal valves and no vegetation on TTE also had a negative TEE [40]. In addition to identification of vegetations, TEE allows evaluation of the severity of valve dysfunction, assessment of left and right ventricular systolic function, estimation of pulmonary pressures, and may detect complications of endocarditis.
TEE has a sensitivity of >90 percent for detection of valvular vegetation and is superior to TTE for detection of cardiac complications such as abscess, leaflet perforation, and aortic pseudoaneurysm or intracardiac fistula. Therefore, TEE is useful in most cases, even if TTE was sufficient to establish the diagnosis of IE [41,42]. Of note, the specificity of TEE is not 100 percent; false-positive findings can occur with cardiac tumors, mural thrombi, or fibrous strands on the aortic valve [3]. (See "Role of echocardiography in infective endocarditis".)
TEE is warranted in the following circumstances [1,3,43,44]:
●TTE without evidence of endocarditis, or TTE technically inadequate, with high clinical suspicion for IE (bacteremia due to an organism known to be a common cause of IE, particularly S. aureus, and/or multiple minor criteria for endocarditis) (table 1 and table 2)
●TTE with valve vegetation, with concern for presence of intracardiac complications such as paravalvular abscess (risk factors include new conduction delay on electrocardiogram, aortic valve endocarditis, and persistent bacteremia or fever despite appropriate antimicrobial therapy)
●TTE with valve vegetation as well as significant valvular regurgitation, to determine need for surgery
Data obtained by TTE and TEE are complementary, so both studies are useful in most patients; however, it is reasonable to forgo TTE and proceed to TEE in the following circumstances:
●A prior valvular abnormality (including previous endocarditis)
●Limited transthoracic windows (eg, due to obesity, chest wall deformity, or mechanical ventilation)
Patients with a negative TEE for whom the clinical suspicion for IE remains high (eg, patients who are at high risk IE and have persistent bacteremia or fever without another identifiable source, and/or multiple minor criteria for IE) should undergo repeat TEE approximately one week later [1,45]. Repeat TEE is also warranted after an initial positive TEE if clinical features suggest new development of an intracardiac complication [1].
If TTE and TEE are both nondiagnostic, cardiac CT is useful for evaluation of paravalvular infection. (See 'Other imaging tools' below.)
Other imaging tools — Additional cardiac imaging tools for diagnosis of IE include cardiac CT and fluorodeoxyglucose positron emission tomography with CT (FDG PET/CT).
Cardiac CT may be helpful for cases in which definitive evidence of IE and its complications cannot be demonstrated with TEE, and/or for planning surgery in patients with extravalvular complications. Cardiac CT may be more informative than TEE when TEE is limited by artifact [46-49]. Cardiac CT may be superior to TEE for evaluation of paravalvular extension of infection and abscess [47], although it is inferior to TEE for detecting vegetations [50]. If clinically warranted, CT imaging of the brain and/or torso may be obtained at the same time to evaluate for evidence of systemic embolization [51]. (See 'Overview of diagnostic approach' above.)
There may be clinical scenarios in which FDG PET/CT can be useful for diagnosis of patients with native valve IE; however, this modality is of greater value for diagnosis of prosthetic valve IE [2]. In one study including 70 patients with suspected NVE, FDG PET/CT led to a modification in management (mostly antibiotic treatment) in 31 percent of cases [52]. In a metanalysis including 13 studies and 537 patients who underwent FDG PET/CT, the sensitivity and specificity for diagnosis of endocarditis were 77 and 78 percent, respectively [53].
DIFFERENTIAL DIAGNOSIS — The differential diagnosis for endocarditis is broad and should be considered based on two clinical categories: presence of bacteremia in the absence of valvular vegetation and presence of valvular vegetation(s) in the absence of bacteremia.
Patients with bacteremia in the absence of evidence for valvular vegetation should be evaluated for alternative causes of bacteremia (which may coexist with IE), including:
●Intravascular catheter infection – Catheter-related infection should be suspected when bacteremia occurs in the setting of a central venous catheter with no other apparent source. The diagnosis is established based on evaluation of samples drawn from the catheter and a peripheral vein. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
●Cardiac device infection – Cardiac device infection should be suspected in the setting of an implanted device with overlying inflammation. Echocardiography is warranted to evaluate for device-related endocarditis. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Forms of infection'.)
●Prosthetic joint infection – Prosthetic joint infection should be suspected in the setting of a prosthetic joint with local erythema or tenderness. Evaluation of joint fluid or tissue is required to establish the diagnosis. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Hematogenous osteomyelitis – Hematogenous osteomyelitis should be suspected in the setting of focal pain at an involved site. Evaluation with radiographic imaging is warranted; the involved pathogen may be established by bone biopsy. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Hematogenous osteomyelitis'.)
●Septic thrombophlebitis – Septic thrombophlebitis should be suspected in the setting of persistent bacteremia in the presence of an intravascular catheter or prior intravascular catheter. Patients may present with erythema, edema, palpable cord, or drainage from the site of the involved vessel. (See "Catheter-related septic thrombophlebitis".)
●Infected arterial aneurysm – An infected arterial aneurysm should be suspected in patients with a risk factor for arterial injury (such as recent vascular procedure, history of endocarditis), pre-existing aneurysm, or presence of a vascular graft. (See "Overview of infected (mycotic) arterial aneurysm".)
Patients with valvular vegetation(s) or arterial emboli in the absence of bacteremia may have culture-negative endocarditis or sterile vegetation(s) (marantic endocarditis or Libman-Sachs endocarditis) due to a noninfectious etiology or antiphospholipid syndrome (see "Diagnosis of antiphospholipid syndrome").
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of infective endocarditis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Endocarditis (The Basics)")
SUMMARY
●Definition and risk factors − Native valve infective endocarditis (IE) refers to infection of the endocardial surface of the heart; it usually refers to infection of one or more heart valves. Risk factors for IE include cardiac factors (history of prior IE or history of valvular or congenital heart disease) and noncardiac factors (intravenous drug use, indwelling intravenous catheter, immunosuppression, or a recent dental or surgical procedure). (See 'Risk factors' above.)
●Clinical manifestations – The clinical manifestations of IE are highly variable; IE may present as an acute, rapidly progressive infection or as a subacute or chronic disease with low-grade fever and nonspecific symptoms. Fever is the most common symptom of IE (up to 90 percent of cases); it is often associated with chills, anorexia, and weight loss. Other symptoms of IE include malaise, headache, myalgias, arthralgias, night sweats, abdominal pain, dyspnea, cough, and pleuritic pain. Cardiac murmurs are observed in approximately 85 percent of patients. Supportive signs include cutaneous manifestations such as petechiae (picture 1) or splinter hemorrhages (picture 2). (See 'Clinical manifestations' above.)
●Complications – IE is associated with a broad array of systemic complications; these include cardiac and neurologic complications, septic emboli, metastatic infection, and systemic immune reactions. Clinical manifestations reflecting these complications may be present at the time of initial presentation and/or may develop subsequently. Clinical manifestations of a complication of IE warrant independent diagnostic evaluation, concurrent with evaluation for IE. (See 'Complications as presenting symptoms' above.)
●Diagnostic approach
•Clinical suspicion – The diagnosis of IE should be suspected in patients with bacteremia due to an organism with known propensity to cause endocarditis; other important clues include fever, relevant cardiac risk factors (prior IE, history of valvular, or congenital heart disease), and other predisposing conditions (intravenous drug use, indwelling intravenous lines, immunosuppression, or a recent dental or surgical procedure). (See 'Overview of diagnostic approach' above.)
•Establishing a diagnosis – The diagnosis of IE is established based on clinical manifestations, blood cultures (or other microbiologic data), and echocardiography. The accepted criteria for diagnosis of IE are the modified Duke criteria, which are summarized above and in the tables (table 1 and table 2) (calculator 1). (See 'Overview of diagnostic approach' above and 'Diagnostic (modified Duke) criteria' above.)
●Blood cultures: Collection and interpretation
•Obtaining blood cultures and empiric treatment – At least three sets of blood cultures should be obtained from separate venipuncture sites prior to initiation of antibiotic therapy. For patients who are clinically stable, antimicrobial therapy may be deferred while awaiting the results of blood cultures and other diagnostic tests. For patients with signs of clinical instability, initiation of empiric antimicrobial therapy (after three blood cultures have been obtained) is appropriate. (See 'Overview of diagnostic approach' above.)
•Typical microorganisms – Typical microorganisms consistent with IE include Staphylococcus aureus, viridans streptococci, Streptococcus gallolyticus (formerly S. bovis), HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) organisms, or community-acquired enterococci. (See 'Diagnostic (modified Duke) criteria' above.)
•Culture-negative IE – Culture-negative IE should be suspected in patients with negative blood cultures and persistent fever with one or more clinical findings consistent with infective endocarditis (eg, stroke or other manifestations of emboli). Culture-negative IE should also be suspected in patients with vegetation on echocardiogram and no clear microbiologic diagnosis. (See 'Culture-negative endocarditis' above.)
●Echocardiography – Echocardiography should be performed in patients with suspected IE (table 1 and table 2 and algorithm 1 and algorithm 2). In general, transthoracic echocardiography (TTE) is the first diagnostic test for patients with suspected IE. Transesophageal echocardiography (TEE) has higher sensitivity than TTE and is better for detection of cardiac complications such as abscess, leaflet perforation, and pseudoaneurysm. In some circumstances, it is reasonable to forgo TTE and proceed to TEE. (See 'Echocardiography' above.)
●Additional evaluation – Additional evaluation for patients with suspected IE includes electrocardiography, chest radiography, other radiographic imaging tailored to clinical manifestations, and dental evaluation. (See 'Overview of diagnostic approach' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Vance G Fowler, Jr, MD, who contributed to earlier versions of this topic review.
