Infective Endocarditis
Definition
Infective endocarditis (IE) is a microbial infection of the cardiac endothelium, most commonly involving the heart valves, though it may involve prosthetic material, intracardiac devices, or mural endocardium. It is characterised pathologically by vegetations — infected thrombotic masses on valve leaflets or surrounding structures. A positive blood culture is a major clinical criterion for confirming IE and typically the first diagnostic clue.
Key Concepts
Duke-ISCVID Diagnostic Criteria (2023 Update)
The Duke criteria (1994) → Modified Duke (2000) → 2023 Duke-ISCVID (most current) represent the standard case definition framework. sources/BCNE-AHA-2025 (rating: high)
Major criteria (2023 version) include:
- Positive blood culture for typical IE microorganisms
- Nucleic acid detection of Coxiella burnetii, Tropheryma whipplei, or Bartonella spp; OR serologic evidence of Bartonella henselae or B. quintana (IgG ≥1:800)
- Amplicon/metagenomic sequencing and in situ hybridisation of tissue specimens
- Surgical Evidence (new 2023): direct inspection during cardiac surgery documenting IE findings
- Echocardiographic evidence of endocardial involvement (vegetation, abscess, new valvular regurgitation, new prosthetic dehiscence)
- Advanced imaging evidence (18F-FDG PET/CT, WBC SPECT/CT) in prosthetic valve or device IE
Minor criteria (2023 additions):
- Positive nucleic acid–based test for an organism consistent with IE from a sterile body site other than cardiac tissue
- Single skin coloniser identified by PCR on a valve/wire without additional supporting evidence (interpreted with caution)
Clinical Presentation
- Classic features: fever, new/changed heart murmur, embolic phenomena (Janeway lesions, Osler nodes, splinter haemorrhages, cerebrovascular events, glomerulonephritis)
- Acute (days–weeks): typically Staphylococcus aureus; subacute (weeks–months): streptococci, enterococci, fastidious organisms
- Euthermic endocarditis occurs in a minority, particularly older patients — absence of fever does not exclude IE sources/BCNE-AHA-2025 (rating: high)
Echocardiography
- TEE superior to TTE for most IE diagnoses, particularly vegetations, perivalvular abscess, fistula, and prosthetic valve involvement
- Indications for surgical evaluation include: heart failure, severe valve dysfunction, paravalvular abscess or fistula, recurrent embolisation, large mobile vegetations, or persistent sepsis despite ≥7 days of adequate antibiotics sources/BCNE-AHA-2025 (rating: high)
Advanced Imaging
- Cardiac CT: comparable sensitivity to TEE for large vegetations, perforation, abscess, pseudoaneurysm, prosthetic dehiscence
- 18F-FDG PET/CT: pooled sensitivity 76.8%/specificity 77.9% (native valve); 80.5%/73.1% (prosthetic valve); one study found only 22% sensitivity for native valve IE but 93% for prosthetic valve sources/BCNE-AHA-2025 (rating: high)
- WBC SPECT/CT: high specificity, limited native valve sensitivity; both modalities allow whole-body extracardiac infection detection
- Role upgraded to major/minor criterion in 2023 Duke-ISCVID for prosthetic/device IE
Microbiology
- Most common pathogens: methicillin-susceptible staphylococci, streptococci, enterococci
- Up to 30% of IE cases have negative blood cultures (see concepts/Blood-Culture-Negative-Endocarditis)
- Optimal blood cultures: 2–3 sets (8–10 mL/bottle; ≥40 mL total); aseptic technique; separate venipunctures preferred though no longer required by 2023 criteria sources/BCNE-AHA-2025 (rating: high)
Surgical Principles
- Excised valve tissue: always send for bacterial/fungal/mycobacterial cultures, pathology; add 16S PCR and broad-range metagenomics when available
- Pathologic evaluation: gross review, immunohistochemistry (T. whipplei, Bartonella, C. burnetii), fluorescence in situ hybridisation
- Early infectious diseases and cardiac surgery consultation critical for optimal timing sources/BCNE-AHA-2025 (rating: high)
Nonbacterial Thrombotic Endocarditis (NBTE)
- Noninfectious vegetations from hypercoagulable/inflammatory states: malignancy, SLE, antiphospholipid antibody syndrome
- Presents with embolic events (stroke 54–59%); fever typically absent; women predominate (mean age 54–60y)
- Activated PTT prolongation is a useful simple marker for antiphospholipid/SLE-associated NBTE
- Can satisfy 2023 Duke-ISCVID criteria without positive cultures — important differential in BCNE sources/BCNE-AHA-2025 (rating: high)
Prevention
- IE prophylaxis for at-risk patients undergoing high-risk dental/surgical procedures
- Critical prevention message: obtain ≥2 blood culture sets before starting any antibiotics to avoid BCNE sources/BCNE-AHA-2025 (rating: high)
Antibiotic prophylaxis
Prophylaxis is restricted to the highest-risk groups, and to dental procedures involving gingival or periapical manipulation or mucosal perforation: prosthetic valve or prosthetic material (including transcatheter valves, annuloplasty rings and clips), durable mechanical circulatory support, previous or recurrent IE, defined congenital heart disease subsets (unrepaired cyanotic CHD; repaired CHD with prosthetic material within 6 months; residual shunt or regurgitation; surgical or transcatheter pulmonary valve), and cardiac transplant recipients with valvulopathy. (sources/Handbook-HA-2024, rating: high)
| Situation | Regimen | Single dose 30–60 min before |
|---|---|---|
| Oral route | Amoxicillin | 2 g |
| Unable to take oral | Ampicillin; or cefazolin / ceftriaxone | 2 g IM/IV; 1 g IM/IV |
| Penicillin-allergic, oral | Cephalexin; azithromycin or clarithromycin; doxycycline | 2 g; 500 mg; 100 mg |
| Penicillin-allergic, non-oral | Cefazolin or ceftriaxone | 1 g IM/IV |
(Table: sources/Handbook-HA-2024)
- Clindamycin is no longer recommended as an alternative regimen, because of more frequent and severe reactions than the other agents.
- Cephalosporins are withheld where the penicillin reaction took the form of anaphylaxis, angioedema or urticaria; vancomycin 15–20 mg/kg IV (maximum 2 g) is the substitute.
- Prophylaxis is not recommended for respiratory, gastrointestinal, urogenital, skin or soft-tissue procedures unless performed in the context of established infection — in which case the regimen should cover staphylococci (respiratory, skin) or enterococci (GI/GU).
Contradictions / Open Questions
- The prophylaxis threshold is much narrower than most clinicians assume, and this page's Prevention bullet does not say so. "At-risk patients" becomes an explicit highest-risk list — prosthetic valve or material, prior IE, defined CHD, transplant valvulopathy — with no role for mitral valve prolapse, rheumatic valve disease, or most native valve disease. (sources/Handbook-HA-2024, rating: high)
- Empiric antibiotic regimens for BCNE vary substantially between US and European guidelines with no RCT evidence to favour one approach over another sources/BCNE-AHA-2025 (rating: high)
- Sensitivity of 18F-FDG PET/CT for native valve IE remains poorly defined with one study reporting only 22% sensitivity vs earlier meta-analysis estimates of 76.8% sources/BCNE-AHA-2025 (rating: high)
- No universally agreed microbial DNA quantification cutoff exists for metagenomic sequencing interpretation in IE sources/BCNE-AHA-2025 (rating: high)
Connections
- Related to concepts/Blood-Culture-Negative-Endocarditis — the BCNE subset
- Related to entities/Atrial-Fibrillation — AF common complication of IE; also IE prophylaxis relevant in rheumatic MS with AF
- Related to entities/ATTR-Amyloidosis — amyloid infiltration can mimic IE vegetations on imaging
- Related to concepts/Valvular-Heart-Disease — IE may develop on diseased native or prosthetic valves
- Related to concepts/Cardiac-Amyloidosis-Imaging — differential for abnormal valve echogenicity