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 leads to 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 according 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 in complex cases (e.g., valve perforation). IE prophylaxis is administered in specific circumstances, e.g., in patients with congenital heart disease having certain dental procedures. IE is typically fatal if left untreated.
|Pathogens causing infective endocarditis (IE)|
Streptococcus gallolyticus subsp. gallolyticus (Sgg) 
Gram-negative HACEK group
Risk factors for infective endocarditis 
- Male sex
- Age > 60 years
- Cardiac conditions
- Noncardiac risk factors
- Damaged valvular endothelium → exposure of the adherence of r →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 (valve regurgitation) 
- Valve involvement 
- Clinical consequences 
“Don't tri drugs for the sake of your tricuspid valves.”
Constitutional symptoms 
- Fever and chills (seen in ∼ 90% of patients) 
- General malaise, weakness, weight loss, night sweats
- Dyspnea, cough, pleuritic chest pain
- Arthralgias, myalgias
A high index of suspicion is required in patients with risk factors for IE, as classic extracardiac manifestations (e.g., , ) are absent in the majority of patients. 
Cardiac manifestations 
- Development of a new heart or change in a preexisting murmur (seen in ∼ 75% of patients) ;
- : early diastolic murmur that is loudest at the; left 3rd and 4thintercostal spaces and along the left sternal border 
- : that is loudest at the heart's apex and radiates to the left axilla
- 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., ). 
Extracardiac manifestations of IE 
Extracardiac manifestations are typically caused by and/or immune complex precipitation and are more commonly seen in left-sided IE, with the exception of pulmonary embolic manifestations, which are more common in right-sided IE. 
Peripheral embolic and immunologic phenomena: seen in only 5–10% of patients. 
- Petechiae, especially splinter hemorrhages (hemorrhages underneath fingernails)
- Janeway lesions
- Osler nodes: painful nodules on pads of the fingers and toes caused by immune complex deposition
- Roth spots: round retinal hemorrhages with pale centers
- Emboli to intraabominal organs
- Neurological manifestations: (e.g., seizures, paresis): due to septic embolic stroke, hemorrhage, meningitis, encephalitis, and/or abscess 
- Pulmonary manifestations: caused by septic emboli resulting from tricuspid valve involvement
- Others: Arthritis
“FROM JANE:” Features of IE include Fever, Roth spots, Osler nodes, Murmur, Janeway lesions, Anemia, Nail bed hemorrhage, and Emboli.
- 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 |
|Native valve endocarditis||Prosthetic valve endocarditis|
|Acute bacterial endocarditis||Subacute bacterial endocarditis|
|Affected valves|| || || |
Classification by location
|Classified by location of valves involved|
|Right-sided endocarditis ||Left-sided endocarditis |
|Distinguishing clinical features|
|Main pathogens|| |
|Affected valves|| || |
- 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. 
- 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.
- Obtain ECG and additional imaging to investigate any complications or new focal symptoms or signs of metastatic infection.
- Consider serology to evaluate blood culture-negative endocarditis.
- Consult infectious disease (ID) if the diagnosis is uncertain.
|Modified Duke criteria |
Laboratory studies 
- CBC: : leukocytosis with left shift
- Inflammatory markers: ↑ CRP, ↑ ESR 
- BMP: to assess renal function for antibiotic dosing
- Urinalysis: to assess for hematuria and nephritic sediment 
See also “Intravascular catheter-related bloodstream infections” and “Bacteremia.”
- Prior to treatment: three sets from different venipuncture sites 
- Monitoring: two sets every 24–48 hours until clearance
- Positive bacterial cultures: Assess according to the modified Duke criteria.
- Negative bacterial cultures do not rule out endocarditis; patients with endocarditis may have a negative result due to: 
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. 
- Indications for TEE include:
- Echocardiographic findings fulfilling Duke criteria for IE: similar in TTE and TEE 
- Other high-risk findings include:
Additional investigations 
- Serology: to assess blood-culture negative endocarditis (in consultation with the infectious disease service)
- Tissue sampling (after surgery)
- ECG: indicated in every patient to assess for complications (e.g., AV block/branch blocks in paravalvular extension) 
Additional imaging: performed in selected cases to assess for complications (e.g., emboli)
- CXR: The presence of multiple pulmonary infiltrates may suggest right-sided IE. 
- Abdominal ultrasound: if splenic abscess or infarction is suspected
- Cardiac CTA: to assess perivalvular disease or coronary artery anatomy prior to cardiac surgery 
- MRI head: Consider for the assessment of intracranial septic emboli.
- 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
Obtain an ECG in all patients with suspected IE to assess for new conduction abnormalities (e.g., AV block, bundle branch block) that suggest the development of a perivalvular or myocardial abscess. Consider urgent cardiac imaging (e.g., TEE, cardiac MRI) if these abnormalities are present. 
- Acute disease (leading to valve insufficiency, septic embolic infarcts, tendinous cord rupture) 
- Chronic disease (leading to valve insufficiency and valve stenosis) 
Noninfective endocarditis (nonbacterial thrombotic endocarditis) 
- 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 
- Malignancy (e.g., pancreatic adenocarcinoma)
- Hypercoagulable states
- Underlying trauma (e.g., from indwelling vascular catheters)
- Previous rheumatic fever
- Autoimmune conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome) 
- Chronic infections (e.g., TB, pneumonia, osteomyelitis)
- Clinical features
- 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
- Anticoagulation with heparin
- Treatment of the underlying condition
Prosthetic valve thrombosis 
- Usually affects mechanic valves
- Rare if anticoagulation is adequate
- Etiology: insufficient anticoagulatory therapy after valve replacement
- Clinical features
- Diagnostics: transesophageal echocardiography
- Anticoagulation and fibrinolysis
- Surgical valve replacement
The differential diagnoses listed here are not exhaustive.
Initial management 
- Unstable patients: Use the and initiate as needed.
- Consult infectious disease early to plan treatment and evaluate the need for empiric therapy.
- Identify patients with .
- Antibiotic therapy
- Supportive care: Treat urgent complications (e.g., acute heart failure, heart block) and initiate management of the underlying cause (e.g., ).
- Management of antithrombotic agents 
- Management of cardiovascular complications: See “ ” and “ .” 
- and 
- Management of if IE is related to IV drug use. 
- Inpatient dental evaluation
- Choice of empiric agent: Consult infectious diseases and take into account patient and disease factors as well as local and individual flora and resistance patterns (see “ " and “Classification”).
- Common empiric antibiotic regimens
|Empiric antibiotic therapy for infective endocarditis |
|Valve type||Clinical presentation||Common regimen|
|Native valve endocarditis||(days)|
|Prosthetic valve endocarditis||≤ 1 year after valve placement|
|> 1 year after valve placement|
Targeted antibiotic therapy based on culture and sensitivity results is recommended for all patients with IE.
Common targeted antibiotic regimens
- ; : beta-lactam (e.g., penicillin G, ampicillin)
- Enterococci: combination therapy (e.g., ampicillin PLUS gentamicin)
- HACEK: ceftriaxone (first-line)
- Duration of therapy: variable depending on many factors, e.g., drug regimen, affected valve; can be 2–6 weeks or longer after the first sterile blood culture
- Blood culture-negative endocarditis: empiric therapy until additional investigations (e.g., serology) yield results
|Targeted antimicrobial therapy for infective endocarditis |
|Organism||Native valve endocarditis (common regimens)||Prosthetic valve endocarditis (common regimens)|
|Methicillin-susceptible staphylococci (e.g., MSSA)|
|Methicillin-resistant staphylococci (e.g., MRSA)|
|Viridans group streptococci, S. gallolyticus|
|Enterococcus spp. (penicillin-sensitive)|
|Enterococcus spp. (penicillin-resistant)|
These procedures typically follow a multidisciplinary decision made by cardiology, cardiothoracic surgery, and infectious disease services.
Indications for surgery consult in IE include:
- Prosthetic valve endocarditis
- Valve dysfunction leading to heart failure
- Uncontrolled infection: e.g., enlarging vegetation, persistent bacteremia
- Perivalvular extension or complications: e.g., abscess, pseudoaneurysm, fistula, heart block
- Fungal endocarditis
- High embolic risk: e.g., mobile vegetation > 10 mm, recurrent embolism
- Surgical options: valve replacement or valve repair (see “Treatment” in “Valvular heart diseases”)
Surgical intervention is required in 50–60% of patients with IE. 
- Perform ABCDE survey.
- Begin treatment of complications causing hemodynamic instability, e.g.:
- (e.g., due to )
- Perform a clinical evaluation, including cardiac surgical history (e.g., date and type of valvular repair or replacement) and screening for .
- Establish IV access, draw three sets of blood cultures from different venipuncture sites, and obtain routine laboratory studies (e.g., CBC, BMP).
- Order echocardiogram.
- Use the to categorize the diagnostic likelihood of IE.
- Obtain ECG and screen for new conduction abnormalities.
- Consult infectious diseases.
- Start after blood samples are obtained.
- Screen for clinical features of CXR, CT abdomen and pelvis, CT head). and consider imaging to confirm their presence (e.g.,
- Identify patients with .
- Switch to blood culture results are available. once
- Begin treatment of underlying conditions (e.g., opioid use disorder) and , treat
- Admit to hospital.
- Screen and monitor for complications (e.g., valvulopathy, acute heart failure, perivalvular abscess, AV block, stroke, pulmonary embolism).
- Cardiac complications
- Embolic complications
- Metastatic infections: due to septic emboli or bacteremia
- Acute kidney injury: Often multifactorial 
We list the most important complications. The selection is not exhaustive.
Endocarditis prophylaxis 
Prophylaxis is indicated prior to certain procedures with a high risk of bacteremia in patients with high-risk cardiac features. 
Cardiac risk factors requiring IE prophylaxis (for procedures that may cause bacteremia)
- Presence of prosthetic cardiac valve or material
- History of endocarditis
- Certain types of congenital heart disease (CHD), e.g., unrepaired cyanotic CHD, repaired CHD (within 6 months of repair), repaired CHD with residual post-operative shunt or regurgitation
- Valvulopathy in cardiac transplant recipients 
- Procedures requiring IE prophylaxis in patients at risk for IE
- Common regimens (usually administered 30–60 minutes prior to the procedure) 
IE prophylaxis is not routinely recommended prior to nondental procedures (including respiratory, skin, musculoskeletal, gastrointestinal, and genitourinary procedures) unless infected tissue is present.