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Infective endocarditis

Last updated: October 5, 2021

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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.


Pathogens causing infective endocarditis (IE)
Main pathogens Characteristics

Staphylococcus aureus

  • Approx. 35 – 40% of native valve IE cases [1]
  • Most common cause of acute IE, including IV drug users and patients with prosthetic valves or pacemakers/ICDs [2][3]
  • Typically affects healthy valves.
  • Usually fatal within 6 weeks if left untreated

Viridans streptococci

Staphylococcus epidermidis

Enterococci (especially Enterococcus faecalis)

  • Approx. 10% of native valve IE cases [1]
  • Multiple drug resistance
  • Common cause of IE following nosocomial UTIs
  • Causes native and prosthetic valve IE
  • Following gastrointestinal or genitourinary procedures

Streptococcus gallolyticus subsp. gallolyticus (Sgg) [5]

Gram-negative HACEK group

  • Less than 5% of native valve IE cases [1][6]
  • Physiological oral pharyngeal flora
  • In patients with poor dental hygiene and/or periodontal infection

Fungal endocarditis (Candida, Aspergillus fumigatus) [7][8]

  • Less than 5% of native valve IE cases [1]
  • At risk groups

Coxiella burnetii

Bartonella species

  • Less than 5% of native valve IE cases [1]
  • Gram-negative pathogens responsible for culture-negative endocarditis

Risk factors for infective endocarditis [1][4][10]

“Don't tri drugs for the sake of your tricuspid valves.”

Constitutional symptoms [1][12]

Cardiac manifestations [1][12]

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.

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.

  • 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]
Native valve endocarditis Prosthetic valve endocarditis
Acute bacterial endocarditis Subacute bacterial endocarditis
Clinical features
  • Early-onset: ≤ 1 year after surgery
  • Late-onset: > 1 year after surgery
Main pathogens
  • Most common: S. aureus (associated with large vegetations that can destroy the valves)
  • Others: group A hemolytic streptococci, S.pneumoniae, N.gonorrhoeae
Affected valves
  • Healthy native valves
  • Native valves with prior injury or congenital defects

Classification by location

Classified by location of valves involved
Right-sided endocarditis [16] Left-sided endocarditis [15]
Distinguishing clinical features
Main pathogens
Affected valves
  • Tricuspid
  • Pulmonic
  • Mitral
  • Aortic

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]
Criteria Findings
  • Predisposing condition (e.g., underlying heart abnormality, IV drug use) [19]
  • Fever > 38°C (100.4F)
  • Vascular abnormalities
  • Immunologic phenomena
  • Microbiology: positive blood cultures not fulfilling major criteria or serological evidence of infection with common organisms
  • Microorganisms demonstrated by tissue culture or histology
  • Characteristic histologic features of active endocarditis

Diagnostic category
Definite IE
if any of the following are present:
≥ 2 major criteria
≥ 1 major criterion PLUS ≥ 3 minor criteria
≥ 5 minor criteria

≥ 1 pathological criterion
Possible IE if any of the following are present:
≥ 1 major criterion PLUS ≥ 1 minor criterion
≥ 3 minor criteria
Rejected diagnosis if:
Criteria for definite or possible IE not fulfilled
Firm alternative diagnosis present
Resolution of clinical characteristics in ≤ 4 days of antimicrobial therapy
Absence of surgical or autopsy evidence of IE

Laboratory studies [15]

Routine studies

Blood cultures [20]

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:
    • Presence of high-risk features
    • TTE findings inconclusive or suggestive of IE
    • Preoperative planning
    • Concern for intracardiac complications (e.g., abscess)
  • Echocardiographic findings fulfilling Duke criteria for IE: similar in TTE and TEE [6][22][23]
  • Other high-risk findings include:

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]

  • Acute disease (leading to valve insufficiency, septic embolic infarcts, tendinous cord rupture) [27]
  • Chronic disease (leading to valve insufficiency and valve stenosis) [27]

Noninfective endocarditis (nonbacterial thrombotic endocarditis) [28][29]

Prosthetic valve thrombosis [31]

The differential diagnoses listed here are not exhaustive.

General principles [6][15][32][33]

Therapeutic approach to infective endocarditis [6][15][32][33]
Management Recommendations
  • Consult infectious diseases (ID) early to plan treatment and evaluate the need for empiric therapy.
  • Identify patients requiring surgery consult (e.g., prosthetic valve endocarditis).
Empiric antibiotics
Targeted antibiotics
Antithrombotic therapy

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]
Valve type Clinical presentation Common regimen
Native valve endocarditis Acute bacterial endocarditis (days)
Subacute bacterial endocarditis (weeks)
Prosthetic valve endocarditis ≤ 1 year after valve placement
> 1 year after valve placement

Targeted antibiotic therapy [15]

Targeted antimicrobial therapy for infective endocarditis [15]
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)

Surgery [15][32]

These procedures typically follow a multidisciplinary decision made by cardiology, cardiothoracic surgery, and infectious disease services.

Endocarditis prophylaxis [32][34]

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