Predisposing cardiovascular factors increasing risk for IE ^[2]:

• The endocardium is a thin layer of endothelial cells lining the inner surface of the heart chambers and valves.
• It is continuous with the endothelium of the great vessels.
• Valve leaflets are avascular — they depend on diffusion from flowing blood for nutrients and have limited immune surveillance. This is why infections here are hard to eradicate.

Valve involvement in IE: MV >> AV > TV (common in IVDA) > PV ^[4].

The hallmark lesion of IE is the vegetation — an irregular mass of platelets, fibrin, inflammatory cells, and microorganisms adherent to the valve surface. It sits on the low-pressure side of the valve:

• Mitral valve: atrial surface (because blood regurgitates into the atrium)
• Aortic valve: ventricular surface

The causative organism depends on whether the IE is acute vs. subacute, native vs. prosthetic valve, and right- vs. left-sided.

• Viridans streptococci remain the most common cause of community-acquired native valve IE in HK.
• S. aureus is increasingly common, driven by healthcare-associated infections (HCAIE).
• MRSA rates in HK are notable (~40% of S. aureus isolates in hospitals), making empiric coverage important.
• IVDU-related IE is less common in HK than in North America/Europe, but still occurs.
• Q fever (Coxiella) is rare in HK; Bartonella and fungal IE are seen in immunosuppressed patients.

• SLE (Libman-Sachs endocarditis) ^[4] — sterile verrucous vegetations, usually on the atrial surface of the mitral valve
• Malignancy (marantic/non-bacterial thrombotic endocarditis, NBTE) ^[4] — associated with mucin-secreting adenocarcinomas; sterile platelet-fibrin thrombi on valves
• Antiphospholipid syndrome — sterile vegetations

Step 1 — Endothelial Damage

• Turbulent blood flow (from regurgitant lesions, congenital shunts, prosthetic materials) damages the valve endothelium.
• Exposed subendothelial collagen activates the coagulation cascade and platelet adhesion.

Step 2 — Non-Bacterial Thrombotic Endocarditis (NBTE)

• Platelets and fibrin deposit on the damaged endothelium, forming a sterile vegetation (NBTE).
• This is the "landing pad" for circulating bacteria.

Step 3 — Bacteraemia

• Transient bacteraemia occurs from dental procedures, skin infections, GI/GU procedures, or IVDU.
• High-virulence organisms (S. aureus) can even seed normal valves; low-virulence organisms (viridans strep) require a pre-existing NBTE.

Step 4 — Bacterial Adherence

• Organisms have specific surface adhesins:
  • S. aureus: fibronectin-binding proteins, clumping factors
  • Viridans strep: dextran production → promotes adherence to platelet-fibrin matrix
  • Enterococci: aggregation substance

Step 5 — Vegetation Growth

• Bacteria proliferate within the platelet-fibrin matrix.
• The vegetation grows, incorporating more fibrin, platelets, inflammatory cells, and bacteria.
• Bacteria deep within the vegetation are protected from both phagocytes and antibiotics (this is why prolonged, high-dose IV antibiotics are required — to penetrate the vegetation).

Step 6 — Three Major Consequences

Both IE and TB are "sneaky" and causes of fever of unknown origin (FUO) ^[2]. In subacute IE, the patient may visit a GP with low-grade fever, receive a short course of oral antibiotics, improve transiently (because antibiotics partially suppress bacteraemia), then relapse weeks later. This cycle can repeat multiple times before diagnosis.

Heart failure is the most common indication for surgery and the most common cause of death in IE. Mechanism:

1. Vegetation → valve destruction → acute severe regurgitation (MR or AR)
2. Unlike chronic regurgitation where the heart adapts (ventricular dilatation, eccentric hypertrophy), acute regurgitation gives no time for compensation
3. Acute MR → sudden volume overload on a non-dilated left atrium → markedly elevated LA pressure → pulmonary congestion → pulmonary oedema
4. Acute AR → sudden volume overload on a non-dilated left ventricle → elevated LVEDP → premature closure of mitral valve → pulmonary oedema

Even without septic emboli, persistent bacteraemia is enough to cause mycotic aneurysm formation within the brain — these are prone to rupture, resulting in a haemorrhagic stroke ^[5].

• "Mycotic" here does NOT mean fungal — it is a historical misnomer. It refers to the mushroom-shaped appearance of the aneurysm.
• Mechanism: bacteria seed the vasa vasorum of cerebral arteries → weakening of the arterial wall → aneurysmal dilatation → risk of rupture.

This is the classical "fever and a murmur" presentation. The DDx pivots on whether the murmur is causative (i.e., the valve itself is the site of pathology) versus incidental (i.e., a pre-existing murmur in a febrile patient):

By the classic Petersdorf–Beeson definition, FUO requires:

• Fever > 38.3°C on several occasions
• Duration > 3 weeks
• No diagnosis after 1 week of inpatient investigation (or 3 outpatient visits)

IE is one of the sneaky causes of FUO, similar to tuberculosis — the patient visits the GP, gets antibiotics, improves transiently, then relapses ^[2]. The DDx of FUO where IE sits:

Why IE causes FUO: Subacute IE produces low-grade continuous bacteraemia from the vegetation. Short courses of oral antibiotics partially suppress but do not sterilise the vegetation (organisms are protected deep within the fibrin-platelet matrix). This gives the illusion of "treatment response" followed by relapse once antibiotics are stopped.

The final common path of all cardiac diseases is heart failure ^[9]. When a patient presents with new HF + fever, the DDx includes:

For the GC case: mitral valve prolapse → mitral regurgitation → backflow into LA → increased LA pressure during systole → congestion of pulmonary vasculature → volume overload of LV → LV dilatation and failure ^[5]. IE superimposed on this pre-existing substrate accelerates valve destruction and precipitates decompensation.

When a patient < 60 years presents with acute ischaemic stroke, IE must be in the DDx because it is a treatable cause of stroke and missing it is catastrophic:

Bacterial endocarditis is an uncommon but important cause of polyarthritis ^[12][13]. IE-related arthritis occurs through two mechanisms: (1) immune complex deposition in synovium, and (2) septic embolisation to joints. The DDx:

IE is an important cause of petechial/purpuric rash in the context of fever ^[14]:

IE-associated GN results from immune complex deposition (with low C3/C4) ^[15]. The DDx of GN with low complement:

Pathologic criteria ^[2][5]:

• Microorganisms demonstrated in a vegetation (by culture or histology of surgically excised valve / embolised vegetation)
• Pathologic lesions = confirmed by histology (vegetation or intracardiac abscess showing active endocarditis)

If either of these is met → Definite IE. This is the gold standard but requires surgical tissue, so most diagnoses in clinical practice rely on the clinical criteria below.

Clinical criteria ^[2][5]:

• Definite IE: 2 major, OR 1 major + 3 minor, OR 5 minor
• Possible IE: 1 major + 1 minor, OR 3 minor ^[7]
• Rejected: firm alternative diagnosis, OR resolution of syndrome with ≤ 4 days of antibiotics, OR no pathological evidence at surgery/autopsy with ≤ 4 days of antibiotics, OR does not meet criteria for possible IE

Major Criteria ^[2][5][7]:

Major 1 — Positive Blood Culture for IE

Blood culture showing persistent bacteraemia of typical organisms ^[2][5]:

Why "persistent" bacteraemia matters: In most infections (pneumonia, UTI, cellulitis), bacteraemia is transient — organisms enter the blood briefly and are cleared by the reticuloendothelial system. In IE, the vegetation acts as a continuous source of bacterial seeding — this is why blood cultures drawn hours apart remain positive. This is the single most important diagnostic feature.

Major 2 — Evidence of Endocardial Involvement

Evidence of endocardial involvement ^[2][5][7]:

Minor Criteria ^[2][5][7]:

The GC case ^[1][5]: 50-year-old man, known MVP, 2-week fever, SOB:

Even before blood culture and echo results, this patient already has ≥ 3 minor criteria → at minimum Possible IE. If blood cultures grow a typical organism (major) or echo shows a vegetation (major), this becomes Definite IE.

Blood culture: at least 3 sets at different sites to demonstrate persistent bacteraemia (typical for IE) ^[4].

Interpreting blood culture results:

Workup for culture-negative IE:

Echocardiogram (TTE/TEE): detect vegetations, valvular lesions, abscesses ^[4].

What echocardiography looks for:

The GC lecture (050) algorithm: clinical suspicion of IE → transthoracic echocardiography as first step ^[17].

CBC, ESR/CRP, RFT, urinalysis for potential GN ^[4].

ECG ^[4][7]:

CXR ^[4][7]:

Give empirically before C/ST to cover at least Staph, Strep & Enterococcus ^[4].

From GC 050: initial management involves antibiotic treatment with ID (Infectious Disease) consultation ^[17].

Treatment of infective endocarditis (antibiotic regime) ^[1][5]:

How to clinically assess how well treatment for IE is going ^[2]:

• Physical signs; body weight
• Urine testing
• Renal function and blood counts
• ESR — may take weeks to decrease; drug level monitoring
• Echocardiogram
• Fever may take 1–2 weeks to decrease

Follow-up blood culture Q3 days (Q48–72h) ^[4] — expected clearance:

• Streptococcal IE: usually within 24–48h of appropriate therapy
• S. aureus IE: typically 3–5 days; if still positive after 5–7 days → consider persistent source, abscess, or need for surgery

Osler's nodes and other peripheral stigmata can persist after treatment for a couple of weeks — so cannot use these physical signs as a marker for treatment success ^[5]. This is because:

• Osler's nodes are immunologically mediated (immune complex deposition) — even after bacteria are cleared, circulating immune complexes take time to be removed
• Use blood culture clearance, fever resolution, CRP/ESR trends, and echocardiographic changes as markers of treatment success instead

Surgical debridement and valvular replacement ^[4]: Indications: haemodynamically unstable, infected prosthesis, persistent infection despite antibiotics ^[4].

Organised by urgency:

High-risk group ^[4]:

• Prosthetic valve replacement / repair
• Previous IE
• Congenital heart disease: unrepaired cyanotic CHD, repaired with residual defects, completely repaired within the first 6 months ^[4]

Why only these groups? They have the highest risk of IE AND the worst outcomes if IE develops. The number needed to treat to prevent one case of IE with prophylaxis is enormously high in lower-risk groups (e.g., MVP without regurgitation), so the risks of antibiotic use (allergy, resistance, C. difficile) outweigh the benefit.

Dental procedures ^[4][20]:

• Any procedure involving manipulation of gingival tissue, periapical region of teeth, or perforation of oral mucosa
• Amoxicillin 2g PO / ampicillin IV; single dose 30–60 min before procedure ^[4]
• Clindamycin 600 mg PO/IV if allergic to penicillin ^[4]

Updated note (2024 HKU Internal Medicine Handbook): Clindamycin is no longer recommended as an alternative antibiotic regime, given more frequent and severe reactions associated with this drug compared with other antibiotic agents ^[20]. In cases of penicillin anaphylaxis/angioedema/urticaria, vancomycin may be used (adults: 15–20 mg/kg IV, not to exceed 2g per dose) ^[20]. Use cephalexin 2g PO or azithromycin 500mg PO as alternatives if no anaphylaxis history.

Other procedures ^[4][20]:

• Antibiotics prophylaxis for IE is generally not recommended for respiratory tract / gastrointestinal / urogenital / skin and soft tissue procedures unless the invasive procedures are performed in the context of infection ^[20]
• Respiratory tract procedure to treat established infection → antibiotic regimen should contain an anti-staphylococcal drug ^[20]
• Established GI/GU tract infection → antibiotic regimen should include an agent active against enterococci ^[20]
• Infected skin / skin structure / musculoskeletal tissue → agent active against staphylococci and beta-haemolytic streptococci ^[20]

For prosthetic valve endocarditis, timing is important — early ( < 3 months) vs. late ( > 3 months) ^[2]:

• Early: usually intraoperative contamination, usually by Staphylococcus ^[2]
• Late: usually caused by organisms representative of normal microbiota — viridans group streptococci and enterococci ^[2]

Management:

• Early surgery often required due to foreign bodies — vegetation growing on valve cannot be cleared well by antibiotics ^[2]
• Vancomycin + gentamicin + rifampicin for ≥ 6 weeks
• Following prosthetic valve surgery, give antibiotic prophylaxis to prevent recurrence ^[2]

• Most commonly tricuspid valve, most commonly S. aureus
• Generally better prognosis than left-sided IE (pulmonary circulation is low-pressure → less haemodynamic consequence)
• Medical therapy alone is successful in ~85–90% of cases
• Consider shorter antibiotic courses (2 weeks) for uncomplicated right-sided S. aureus NVE (MSSA) in select patients: no renal failure, no large vegetations > 2 cm, no extrapulmonary metastatic infection, no HF, no aortic/mitral valve involvement
• Surgery reserved for: vegetation > 2 cm, persistent bacteraemia > 7 days, severe TR with refractory HF, or recurrent septic PE

• If prior antibiotics → withhold (if safe) for 48h and re-culture
• If fastidious organisms suspected → extended incubation, serology (Coxiella, Bartonella, Brucella), 16S rRNA PCR
• If empirical therapy needed → vancomycin + gentamicin ± ceftriaxone to cover Gram-positives and HACEK
• If Coxiella confirmed → doxycycline + hydroxychloroquine for ≥ 18 months (Q fever endocarditis is uniquely difficult to treat)

Heart failure is the MOST common cause of death due to IE in the modern era ^[3].

Mechanism — from first principles:

• Vegetation grows on valve leaflet → bacterial enzymes (proteases, collagenases) and inflammatory infiltrate destroy leaflet tissue → leaflet perforation or chordal rupture
• Result: acute severe valvular regurgitation (MR or AR)
• In acute MR: sudden volume overload on a non-dilated left atrium → markedly elevated LA pressure → transmitted back to pulmonary capillaries → pulmonary oedema → dyspnoea, orthopnoea, bilateral basal crackles
• In acute AR: sudden regurgitant volume overloads a non-dilated LV → dramatically elevated LVEDP → premature mitral valve closure → pulmonary oedema
• Unlike chronic regurgitation (where gradual ventricular remodelling compensates), acute regurgitation gives no time for adaptation → rapid haemodynamic collapse

Why HF is the #1 indication for surgery: medical therapy (diuretics, vasodilators) can temporise but cannot fix a mechanically destroyed valve. The patient deteriorates until the valve is surgically repaired or replaced.

Clinical clues: worsening SOBOE, orthopnoea, PND, new S3, bilateral basal crackles, elevated JVP, displaced apex beat, new or worsening regurgitant murmur ^[1][5].

Aortic valve and adjacent annulus are more susceptible to abscess formation than mitral valve and annulus ^[3].

Mechanism: infection extends from the valve leaflet into the surrounding tissue — the valve annulus and adjacent myocardium. This creates a walled-off collection of pus (abscess). It occurs more commonly at the aortic valve because the aortic annulus is fibrous (avascular) and adjacent to critical structures — the conduction system, mitral valve, and aorta.

Why is this dangerous?

• Abscess may extend into adjacent cardiac conduction tissues leading to heart block ^[3]. The AV node and bundle of His run through the membranous interventricular septum immediately below the aortic valve annulus. An expanding abscess erodes into this region → AV block (first-degree → complete heart block). New AV block on serial ECG in an IE patient = strong suspicion for perivalvular abscess.
• Abscess may rupture into a cardiac chamber → intracardiac fistula
• Abscess may erode into the aortic root → pseudoaneurysm → risk of rupture
• Antibiotics penetrate abscess cavities poorly → almost always requires surgical drainage

Diagnosis: TEE is superior to TTE for detecting abscess (echo-lucent area within the annulus). Cardiac CT is an alternative.

Intracardiac fistulae develop due to extension of infection from valve to adjacent myocardium ^[3].

Mechanism: a perivalvular abscess erodes through the tissue plane between two cardiac chambers, creating an abnormal communication. For example:

• Aortic root abscess → fistula into right atrium or right ventricle → left-to-right shunt → acute volume overload of the right heart and pulmonary circulation
• Aortic root abscess → fistula into left atrium → acute AR directly into LA

Clinical consequence: acute haemodynamic deterioration with new continuous murmur (if systemic-to-right-heart communication) → surgical emergency.

Prosthetic valve endocarditis may be complicated by valvular abscess and conduction system dysfunction ^[21].

Unique aspects of PVE:

• Infection occurs at the sewing ring (the suture line attaching the prosthesis to the native annulus) rather than on the prosthetic leaflets themselves
• Abscess formation at the sewing ring → prosthetic valve dehiscence (rocking motion on echo) → paravalvular regurgitant leak → acute HF
• Vegetation growing on valve cannot be cleared well by antibiotics ^[2] due to biofilm formation on prosthetic material → almost always requires re-operation

For large vegetations ( > 1 cm), these are prone to breaking off, lodging into the brain vasculature and causing ischaemic stroke ^[5].

Mechanism: vegetation fragments (septic emboli) dislodge → travel through the aorta → enter the cerebral arteries (most commonly MCA territory, as the MCA receives the greatest proportion of carotid flow) → occlude the artery → ischaemic infarction of the brain territory supplied.

Clinical features: sudden-onset focal neurological deficit — contralateral hemiparesis, hemisensory loss, aphasia (if dominant hemisphere), visual field defect, neglect.

Key clinical consideration: timing of cardiac surgery after stroke is critical:

• Small ischaemic stroke / TIA → surgery can usually proceed within days
• Large ischaemic stroke → delay surgery 2–4 weeks if possible, because cardiopulmonary bypass (with heparinisation) risks haemorrhagic transformation of the infarct
• If surgery cannot be delayed (e.g., refractory HF) → multidisciplinary decision

Even without septic emboli, persistent bacteraemia is enough to cause mycotic aneurysm formation within the brain — these are prone to rupture, resulting in a haemorrhagic stroke ^[5].

Mechanism of mycotic aneurysm:

1. Bacteria (from persistent bacteraemia or septic emboli) seed the vasa vasorum of cerebral arteries
2. Bacterial infection weakens the arterial wall (destruction of the media and internal elastic lamina)
3. The weakened segment dilates → mycotic aneurysm (the name is a historical misnomer from the mushroom-shaped appearance; it is NOT fungal)
4. The aneurysm ruptures → subarachnoid or intracerebral haemorrhage

Also: haemorrhagic transformation of an ischaemic infarct can occur spontaneously or be precipitated by anticoagulation.

Diagnosis: CT angiography or conventional cerebral angiography to identify the aneurysm. MRI brain is more sensitive for detecting small infarcts.

Management: Neurosurgical or endovascular intervention (clipping or coiling) for unruptured mycotic aneurysms > 7 mm or enlarging on serial imaging. Ruptured aneurysms require emergency intervention. Anticoagulation should generally be avoided.

Mechanism: septic emboli lodge in brain parenchyma → establish focal infection → cerebritis → encapsulated abscess. Multiple abscesses are characteristic of haematogenous spread (as opposed to single abscess from local spread in sinusitis/otitis).

Clinical features: headache (most common symptom), fever, focal neurological deficits, seizures, altered consciousness. Fever may be absent in up to 50%.

Diagnosis: MRI brain with contrast (ring-enhancing lesion with surrounding oedema; restricted diffusion on DWI).

Mechanism: bacteraemia with seeding of the meninges, or rupture of a cerebral abscess into the subarachnoid space. May present with headache, neck stiffness, photophobia, and altered consciousness overlapping with the systemic features of IE.