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Infective endocarditis

Last updated: December 10, 2020

Summary

Infective endocarditis (IE) is an infectious inflammation of the endocardium that affects the 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 endocardium destruction, 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 (ID) 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 is only administered in specific circumstances, e.g., in patients with preexisting heart conditions undergoing dental or surgical procedures. If left untreated, infective endocarditis can be fatal within a few weeks.

Etiology

Pathogens

Main pathogens Characteristics

Staphylococcus aureus (45–65%)
  • Most common cause of acute IE in all groups (including IV drug users and patients with prosthetic valves or pacemakers/ICDs)
  • Affects previously healthy valves
  • Usually fatal within 6 weeks (if left untreated)

Viridans streptococci (30%): S. sanguinis, S. mutans, S. mitis

Staphylococcus epidermidis

Enterococci, especially Enterococcus faecalis (< 10%)

Streptococcus gallolyticus (S. bovis)

Gram-negative HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
  • Physiological oral pharyngeal flora (∼ 3% of cases of IE)
  • In patients with poor dental hygiene and/or periodontal infection

Candida species

Aspergillus fumigatus
  • Causes IE in immunosuppressed patients (e.g., patients with HIV or organ transplantation)
  • Causes IE in IV drug abusers
  • Cause of IE after cardiosurgical interventions and/or long-term indwelling IV catheters

Coxiella burnetii

Bartonella species
  • Gram-negative pathogens responsible for culture-negative endocarditis

HEAving your KING-size bed from IKEa into your CAR AGGREGATes joy: Native valve endocarditis is caused by haemophilus, kingella, eikenella, cardiobacterium, and aggregatibacter.

Risk factors for infective endocarditis

  • Demographics
    • Male sex
    • Age > 60 years
  • Preexisting conditions
  • Bacteremia
    • Infected peripheral venous catheters, surgery, dental procedures
    • Nonsterile venous injections (e.g., IV drug users)
    • Bacterial infections of various organs (e.g., UTIs, spondylodiscitis)

References:[1][2][3][4][5][6][7][8][9][10][11][12][13][14]

Pathophysiology

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

References:[7][15][16][17]

Clinical features

Constitutional symptoms

Cardiac manifestations

Extracardiac manifestations

With the exception of pulmonary embolic manifestations, extracardiac symptoms are more common in left-sided endocarditis.

Infective endocarditis should always be considered as a cause of fever of unknown origin (FUO), especially if a new heart murmur develops!

FROM JANE - Fever, Roth spots, Osler nodes (Ouch = painful), Murmur, Janeway lesions, Anemia, Nail bed hemorrhage, Emboli

References:[1][2][7][16][18][19][20][21][22][23][24]

Classification

Infective endocarditis can be classified based on the type of valve (native vs. prosthetic), acuity of the infection, and 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.

Classified by type of valve involved and clinical course
Native valve endocarditis Prosthetic valve endocarditis
Acute bacterial endocarditis Subacute bacterial endocarditis
Distinguishing 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
Classified by location of valves involved
Right-sided endocarditis [26] Left-sided endocarditis
Distinguishing clinical features
Main pathogens
Affected valves
  • Tricuspid
  • Pulmonic
  • Mitral
  • Aortic

Diagnostics

Approach [25][27]

  • 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. [28]
    • Used as a diagnostic guide; not a substitute for clinical judgment
    • Incorporate clinical, microbiological, pathological, and imaging criteria.
  • All patients require 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 [25][28][29]
Criteria Findings
Major
Minor
  • Predisposing condition (e.g., underlying heart abnormality, IV drug use) [30]
  • 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
Pathological
  • 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 [25]

Routine studies

Blood cultures [31]

Echocardiography [25]

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. [25]

  • 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 [28][33][34]
    • Valvular vegetations: Hyperechoic mobile masses located on the valve, mural endocardium, or prosthetic material [35]
    • Abscess (e.g., perivalvular abscess)
    • New valvular regurgitation (especially with valve prolapse, perforation, or destruction)
    • Prosthetic valve dehiscence
  • Other high-risk findings include:

TEE is more sensitive (∼ 90%) than TTE (∼ 75%) and is more reliable to help exclude IE in patients with moderate-to-high pretest probability.

Additional investigations [25][31]

Pathology

Pathogenesis

  • Acute disease (leading to valve insufficiency, septic embolic infarcts, tendinous cord rupture)
    1. Erosion → fibrin deposits on valves
    2. Ulceration
    3. Perforation → adaptation of valve edges not possible
  • Chronic disease (leading to valve insufficiency and valve stenosis)
    1. Erosion → reorganization of fibrin layer
    2. Granulation tissue → valve scarring/fibrosis
    3. Calcification → thickened and/or shortened tendinous cords


References:[7]

Differential diagnoses

Noninfective endocarditis (nonbacterial thrombotic endocarditis)

Prosthetic valve thrombosis

References:[38][39]

The differential diagnoses listed here are not exhaustive.

Treatment

General principles [25][28][40][41]

Therapeutic approach to infective endocarditis [25][28][40][41]
Management Recommendations
Consults
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 [25]

Empiric antibiotic therapy for infective endocarditis [25]
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 [25]

Targeted antimicrobial therapy for infective endocarditis [25]
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)
HACEK

Surgery [25][40]

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

Prevention

Endocarditis prophylaxis [40][42]

References

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