Summary
Infective endocarditis (IE) is an infection of the endocardium that typically affects one or more heart valves. The condition is usually a result of bacteremia, which is most commonly caused by dental procedures, surgery, distant primary infections, and nonsterile injections. IE may be acute (developing over hours or days) or subacute (progressive over weeks to months). Acute bacterial endocarditis is usually caused by Staphylococcus aureus and causes rapid destruction of endocardial tissue, while subacute bacterial endocarditis is most commonly caused by viridans streptococci and generally affects individuals with preexisting damage to the heart valves, structural heart defects, or prosthetic valves. Clinical features include constitutional symptoms (fatigue, fever/chills, malaise), signs of pathological cardiac changes (e.g., new or changed heart murmur, heart failure signs), and, in some cases, manifestations of subsequent damage to other organs (e.g., glomerulonephritis, septic embolic stroke). Management is complex and infectious disease specialists should be involved early. Diagnosis is made based on the Duke criteria, the main features of which are positive blood cultures and evidence of endocardial involvement on echocardiography. Initial treatment of IE consists of empiric IV antibiotics, which are then adapted to blood culture results and continued for several weeks. Categorization into native valve endocarditis or prosthetic valve endocarditis helps to further tailor regimens. Surgery may be necessary for complex cases (e.g., valve perforation). Prophylaxis against IE is administered in certain circumstances, e.g., in patients with preexisting heart conditions, such as congenital heart disease, undergoing dental or surgical procedures. IE is typically fatal if left untreated.
Etiology
Pathogens
Pathogens causing infective endocarditis (IE) | |
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Main pathogens | Characteristics |
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Enterococci (especially Enterococcus faecalis) |
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Streptococcus gallolyticus subsp. gallolyticus (Sgg) [5] |
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Gram-negative HACEK group |
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Fungal endocarditis (Candida, Aspergillus fumigatus) [7][8] |
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Bartonella species |
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Risk factors for infective endocarditis [1][4][10]
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Demographics
- Male sex
- Age > 60 years
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Cardiac conditions
- Acquired valvular disease (e.g., rheumatic heart disease, aortic stenosis, degenerative valvular disease)
- Prosthetic heart valves
- Congenital heart defects (e.g., VSD, bicuspid aortic valve)
- Previous IE
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Noncardiac risk factors
- Poor dental status
- Dental procedures
- Nonsterile venous injections (e.g., in IV drug use)
- Intravascular devices
- Surgery
- Chronic hemodialysis
- Immunocompromise (e.g., HIV infection, diabetes)
- Other bacterial infections (e.g., UTIs, spondylodiscitis, periodontal infection)
Pathophysiology
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Pathogenesis [1]
- Damaged valvular endothelium → exposure of the subendothelial layer → adherence of platelets and fibrin → sterile vegetation (microthrombus)
- Localized infection or contamination → bacteremia → bacterial colonization of vegetation → formation of fibrin clots encasing the vegetation → valve destruction with loss of function [11]
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Valve involvement [10]
- Frequency of valve involvement: mitral valve > aortic valve > tricuspid valve > pulmonary valve
- The tricuspid valve is the most commonly affected valve in IV drug users (associated with Pseudomonas, S. aureus, and Candida).
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Clinical consequences [1][11]
- Bacterial vegetation → bacterial thromboemboli → vessel occlusion → infarctions
- Emboli can lead to metastatic infections of other organs.
- Formation of immune complexes and antibodies against tissue antigens → glomerulonephritis, Osler nodes
“Don't tri drugs for the sake of your tricuspid valves.”
Clinical features
Constitutional symptoms [1][12]
- Fever and chills, tachycardia
- General malaise, weakness, weight loss, night sweats
- Dyspnea; , cough, pleuritic chest pain
- Arthralgias, myalgias
Cardiac manifestations [1][12]
- Development of a new heart murmur or change in a preexisting murmur
-
Tricuspid valve regurgitation
- Holosystolic murmur that is loudest at the left sternal border
- Seen in IV drug users, immunocompromised individuals, patients with congenital heart disease, and patients with instrumentation in the right heart (e.g., central venous catheters) [2]
- Aortic valve regurgitation: early diastolic murmur that is loudest at the left sternal border
- Mitral valve regurgitation: holosystolic murmur that is loudest at the heart's apex and radiates to the left axilla
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Tricuspid valve regurgitation
- Heart failure (e.g., dyspnea, lower limb edema) due to valve insufficiency
- Arrhythmias: Suspect a perivalvular abscess in patients with IE who develop a new conduction abnormality (e.g., heart block). [13]
Extracardiac manifestations [1][12]
Extracardiac symptoms are more common in left-sided IE, with the exception of pulmonary embolic manifestations, which are more common in right-sided IE. These extracardiac manifestations are mainly caused by bacterial microemboli and/or the precipitation of immune complexes.
- Petechiae, especially splinter hemorrhages (hemorrhages underneath fingernails)
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Janeway lesions
- Small, nontender, erythematous macules on palms and soles
- Microabscesses with neutrophilic capillary infiltration and areas of hemorrhage caused by septic microemboli from valve vegetations
- Osler nodes: painful nodules on pads of the fingers and toes caused by immune complex deposition
- Roth spots: round retinal hemorrhages with pale centers
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Acute renal injury
- Including hematuria and anuria
- Due to renal artery occlusion or glomerulonephritis
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Splenomegaly and possible LUQ pain
- Due to splenic artery occlusion or splenic abscess
- May lead to splenic rupture [14]
- Neurological manifestations; (e.g., seizures, paresis): due to septic embolic stroke, hemorrhages, meningitis, encephalitis, and/or abscess
- Signs of pulmonary embolism (e.g., dyspnea); : typically caused by septic emboli resulting from tricuspid valve involvement
- Arthritis
Infective endocarditis should always be considered as a cause of fever of unknown origin (FUO), especially in the presence of a new heart murmur.
“FROM JANE:” Features of infective endocarditis include Fever, Roth spots, Osler nodes, Murmur, Janeway lesions, Anemia, Nail bed hemorrhage, and Emboli.
Classification
- IE can be classified by:
- Type of affected valve (native vs. prosthetic)
- Acuity of the infection
- Location of the infection (left- vs. right-sided).
- Although this is not a definitive classification system, it can help in the approach to management and selection of empiric antibiotic regimens.
Classification by valve type and duration of infection
Classified by type of valve involved and clinical course [15] | |||
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Native valve endocarditis | Prosthetic valve endocarditis | ||
Acute bacterial endocarditis | Subacute bacterial endocarditis | ||
Clinical features |
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Main pathogens |
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Affected valves |
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Classification by location
Classified by location of valves involved | ||
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Right-sided endocarditis [16] | Left-sided endocarditis [15] | |
Distinguishing clinical features |
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Main pathogens |
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Affected valves |
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Diagnostics
Approach [15][17]
- Suspect IE based on clinical findings (e.g., fever without focus combined with a new murmur) and predisposing conditions.
-
The modified Duke criteria help categorize the diagnostic likelihood of IE: definite vs. possible vs. rejected. [6]
- Used as a diagnostic guide; not a substitute for clinical judgment
- Incorporate clinical, microbiological, pathological, and imaging criteria.
- All patients should receive multiple blood cultures and echocardiography.
- Additional diagnostics (e.g., serology, additional imaging) help assess blood culture-negative endocarditis and complications.
- Consult infectious disease (ID) if the diagnosis is uncertain.
Modified Duke criteria [6][15][18] | |
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Criteria | Findings |
Major |
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Minor |
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Pathological |
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Diagnostic category |
Laboratory studies [15]
Routine studies
- CBC: leukocytosis with left shift
- Inflammatory markers: ↑ CRP, ↑ ESR [17]
- BMP: assessment of renal function for antibiotic dosing
Blood cultures [20]
-
Sampling protocol
- Prior to treatment: 3 sets from different venipuncture sites [15][20]
- Monitoring: 2 sets every 24–48 hours until clearance
-
Interpretation
- Positive bacterial cultures: Assess according to the modified Duke criteria.
- Negative bacterial cultures do not rule out endocarditis. False negatives can be due to: [6][20][21]
- Antibiotic therapy prior to blood culture sampling
- Fastidious bacteria (most commonly Coxiella burnetii and Bartonella spp.)
- Fungal infection
- Noninfective endocarditis
Echocardiography [15]
Transthoracic echocardiography (TTE) is the initial test of choice for all patients with suspected IE. It should ideally be performed within 12 hours of presentation and repeated after completing treatment. Transesophageal echocardiography (TEE) is more invasive and is added in select cases. [15]
- Indications for TEE include:
-
Echocardiographic findings fulfilling Duke criteria for IE: similar in TTE and TEE [6][22][23]
- Valvular vegetations: Hyperechoic mobile masses located on the valve, mural endocardium, or prosthetic material [24]
- Abscess (e.g., perivalvular abscess)
- New valvular regurgitation (especially with valve prolapse, perforation, or destruction)
- Prosthetic valve dehiscence
-
Other high-risk findings include:
- Valve aneurysm
- Fistula or pseudoaneurysm
- Heart failure
TEE is more sensitive (∼ 90%) than TTE (∼ 75%) and is more reliable in ruling out IE in patients with moderate-to-high pretest probability.
Additional investigations [15][20]
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Serology: to assess blood-culture negative endocarditis (in consultation with the infectious disease service)
- Most commonly for Coxiella burnetii and Bartonella spp.
- A C. burnetti anti-phase I IgG titer of ≥ 1:800 is part of the modified Duke criteria.
- Limitations: cross-reactivity between different pathogens, confounding from prior infections
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Tissue sampling (after surgery)
- Histopathology of resected valves (gold standard) [20][25]
- Gram stain and culture: to plan duration of postoperative antimicrobial therapy [20]
- Molecular testing (e.g., T. whipplei PCR) [25]
- ECG: indicated in every patient to assess for complications (e.g., AV block/branch blocks in paravalvular extension) [6][17]
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Additional imaging: in individual cases to investigate for complications (e.g., emboli)
- Abdominal ultrasound: if splenic abscess or infarction is suspected
- Cardiac CTA: to assess perivalvular disease or coronary artery anatomy prior to cardiac surgery [23]
- MRI head: consider for assessment of intracranial septic emboli [26]
- Dental assessment: in all patients with confirmed IE regardless of the initial source of bacteremia
- Colonoscopy: in patients with bacteremia involving S. gallolyticus to rule out colon cancer and mucosal lesions
Pathology
- Acute disease (leading to valve insufficiency, septic embolic infarcts, tendinous cord rupture) [27]
- Chronic disease (leading to valve insufficiency and valve stenosis) [27]
- Erosion → reorganization of fibrin layer
- Granulation tissue → valve scarring/fibrosis
- Calcification → thickened and/or shortened tendinous cords
Differential diagnoses
Noninfective endocarditis (nonbacterial thrombotic endocarditis) [28][29]
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Description
- Rare, noninfective form of endocarditis due to sterile platelet thrombus formation on the heart valves (usually mitral and aortic valves)
- Libman-Sacks endocarditis: a type of noninfective endocarditis with verrucous vegetations in individuals with systemic lupus erythematosus or antiphospholipid syndrome [28]
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Etiology
- Malignancy
- Hypercoagulable states
- Underlying trauma (e.g., from indwelling vascular catheters)
- Previous rheumatic fever
- Autoimmune conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome) [30]
- Chronic infections (e.g., TB, pneumonia, osteomyelitis)
- Clinical features
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Diagnostics
- Negative blood cultures
- Echocardiography: valve vegetations
-
Biopsy (definitive diagnosis)
- Sterile vegetations on either surface of the valve composed of immune complexes, mononuclear cells, and thrombi interwoven with fibrin strands
- Not always feasible, therefore diagnosis is mostly made based on clinical findings, negative blood cultures, echocardiography findings, and no response to antibiotic treatment
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Treatment
- Anticoagulation with heparin
- Treatment of the underlying condition
Prosthetic valve thrombosis [31]
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Overview
- Usually affects mechanic valves
- Rare if anticoagulation is adequate
- Etiology: insufficient anticoagulatory therapy after valve replacement
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Clinical features
- Signs of acute heart failure
- Deterioration of general condition, cardiac arrhythmias, cerebral emboli (stroke)
- Diagnostics: transesophageal echocardiography
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Treatment
- Anticoagulation and fibrinolysis
- Surgical valve replacement
The differential diagnoses listed here are not exhaustive.
Treatment
General principles [6][15][32][33]
Therapeutic approach to infective endocarditis [6][15][32][33] | |
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Management | Recommendations |
Consults |
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Empiric antibiotics |
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Targeted antibiotics |
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Antithrombotic therapy |
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If infective endocarditis is suspected, first obtain blood cultures, then consult ID to plan empiric antibiotic therapy. When culture results are available, adapt the therapy accordingly.
Empiric antibiotic therapy [15]
Empiric antibiotic therapy for infective endocarditis [15] | ||
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Valve type | Clinical presentation | Common regimen |
Native valve endocarditis | Acute bacterial endocarditis (days) |
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Subacute bacterial endocarditis (weeks) | ||
Prosthetic valve endocarditis | ≤ 1 year after valve placement |
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> 1 year after valve placement |
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Targeted antibiotic therapy [15]
Targeted antimicrobial therapy for infective endocarditis [15] | ||
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Organism | Native valve endocarditis (common regimens) | Prosthetic valve endocarditis (common regimens) |
Methicillin-susceptible staphylococci (e.g., MSSA) |
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Methicillin-resistant staphylococci (e.g., MRSA) |
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Viridans group streptococci, S. gallolyticus |
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Enterococcus spp. (penicillin-sensitive) |
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Enterococcus spp. (penicillin-resistant) |
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HACEK |
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Surgery [15][32]
These procedures typically follow a multidisciplinary decision made by cardiology, cardiothoracic surgery, and infectious disease services.
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Indications for surgical consultation include:
- Prosthetic valve endocarditis
- Valve dysfunction
- Signs/symptoms of heart failure
- New heart block
- Annular or aortic abscess or destructive penetrating lesions
- Fungal endocarditis
- Complications secondary to perivalvular extension: e.g., abscess, pseudoaneurysm, fistula
- Options: valve replacement or valve repair (See “Treatment” in “Valvular heart diseases”.)
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Complications
- Acute surgical complications: e.g., rebleeding from surgical sites, coagulopathy, acute renal failure, pneumonia
- Cardiac complications: e.g., CHF, myocarditis, pericarditis, new AV block
- Systemic emboli: e.g., stroke
Prevention
Endocarditis prophylaxis [32][34]
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Common indications [35][36]
- Prior to the implantation of cardiac implantable electronic devices (e.g., AICD) [37]
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Some dental procedures in patients with high-risk cardiac features, such as:
- Prosthetic heart valves or prosthetic material used for valve repair
- History of endocarditis
- Types of congenital heart disease (CHD): e.g.., unrepaired cyanotic CHD, Repaired CHD with shunt or regurgitation at or near the site of prosthetic material
- Cardiac transplant with valve regurgitation
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Common regimens (usually administered 30–60 minutes prior to the procedure)
- Prior to cardiac device implantation: cefazolin
- Prior to dental procedures
- No penicillin allergy: amoxicillin OR ampicillin
- Penicillin allergy: a macrolide (e.g., azithromycin ) OR clindamycin