Key Facts

Infective endocarditis (IE) is an infection of the endocardial surface of the heart, most commonly involving the heart valves. Vegetations composed of platelets, fibrin, microorganisms, and inflammatory cells form on damaged endocardium.

Epidemiology

• Incidence: ~3-10 per 100,000 per year in the UK
• Increasing incidence due to: ageing population, prosthetic valves, cardiac devices, IV drug use, healthcare-associated infections
• Male:female ratio ~2:1
• Median age: 50-60 years (increasing)

Aetiology

Organisms:

• Staphylococcus aureus: most common overall; acute presentation; IVDU-associated
• Viridans group streptococci (S. mitis, S. sanguinis): subacute native valve IE; dental origin
• Enterococcus faecalis: elderly, urogenital/GI source
• Coagulase-negative staphylococci: prosthetic valve IE (especially early <12 months)
• HACEK organisms: slow-growing gram-negatives; culture-negative IE
• Coxiella burnetii (Q fever): commonest cause of culture-negative IE in UK
• Fungi: Candida, Aspergillus — immunocompromised, prosthetic valves

Risk factors:

• Pre-existing valve disease, prosthetic valve, previous IE
• IV drug use (right-sided IE: tricuspid valve)
• Cardiac devices (pacemaker/ICD leads)
• Poor dental hygiene, dental procedures
• Immunosuppression, diabetes, CKD/dialysis
• Healthcare-associated (IV lines, procedures)

Pathophysiology

• Damaged endothelium → platelet-fibrin thrombus deposition (non-bacterial thrombotic endocarditis)
• Bacteraemia allows organisms to colonise the thrombus → vegetation formation
• Vegetations: friable, can embolise to brain, kidneys, spleen, lungs (right-sided IE), skin
• Local invasion: valve destruction, abscess formation, fistulae
• Immune complex deposition: glomerulonephritis, Osler nodes, Roth spots

Acute IE (S. aureus)

• Rapid onset, high fever, rigors
• Rapid valve destruction → acute heart failure
• Large vegetations, high embolic risk
• Septic shock in severe cases

Subacute IE (Viridans streptococci)

• Insidious onset over weeks-months
• Low-grade fever, night sweats, weight loss, fatigue, malaise
• New or changing murmur
• Embolic phenomena develop gradually

Peripheral Stigmata (Exam Favourites)

• Janeway lesions: painless erythematous macules on palms/soles (septic emboli)
• Osler nodes: painful nodules on finger/toe pulps (immune-mediated)
• Splinter haemorrhages: linear haemorrhages in nail beds
• Roth spots: retinal haemorrhages with pale centres
• Petechiae: skin, conjunctivae, oral mucosa
• Splenomegaly
• Clubbing (in chronic/subacute cases)

Red Flags

• New murmur with fever
• Stroke or peripheral embolism in a febrile patient
• Heart failure with fever
• Persistent bacteraemia (blood cultures positive >48 hours on appropriate antibiotics)
• Prosthetic valve with fever

Bedside

• Temperature chart: persistent/relapsing fever
• Urinalysis: haematuria (glomerulonephritis, renal infarct)
• ECG: new conduction abnormalities (suggests aortic root abscess)
• Fundoscopy: Roth spots

Bloods

• Blood cultures: 3 sets from different sites at different times BEFORE antibiotics
• FBC: normocytic anaemia, leucocytosis, thrombocytopenia
• CRP/ESR: markedly elevated
• U&Es: renal function (embolic infarcts, nephritis, gentamicin toxicity)
• LFTs: hepatic congestion
• Complement levels (C3, C4): low in immune complex GN
• Rheumatoid factor: positive in ~50% of subacute IE (immune complexes)
• Procalcitonin: may help differentiate from non-infectious causes

Imaging

• Transthoracic echocardiography (TTE): first-line; sensitivity ~60-70% for vegetations
• Transoesophageal echocardiography (TOE): sensitivity ~90-95%; essential if TTE negative but clinical suspicion high, prosthetic valve IE, suspected abscess/complications
• CT abdomen/pelvis: splenic abscess/infarct, renal infarct
• MRI brain: mycotic aneurysm, cerebral abscess, embolic infarcts
• PET-CT: increasingly used for prosthetic valve/device IE (modified Duke criteria)

Special Tests

• Serology: Coxiella, Bartonella, Brucella, Legionella (if culture-negative)
• 16S rRNA PCR on valve tissue: identify organisms in culture-negative cases

Modified Duke Criteria

Definite IE: 2 major, or 1 major + 3 minor, or 5 minor criteria Major criteria:

1. Positive blood cultures (typical organism from 2 separate cultures, or persistently positive)
2. Positive echo (vegetation, abscess, new valve dehiscence) or new valvular regurgitation

Minor criteria:

1. Predisposing heart condition or IVDU
2. Fever ≥38°C
3. Vascular phenomena (emboli, Janeway lesions, mycotic aneurysm, conjunctival haemorrhage)
4. Immunological phenomena (Osler nodes, Roth spots, GN, positive RF)
5. Positive blood cultures not meeting major criteria
6. Positive echocardiographic findings not meeting major criteria

Non-pharmacological

• Source identification and control: dental assessment, remove infected lines/devices
• MDT approach: cardiology, microbiology, cardiac surgery
• Serial echocardiography to monitor vegetation size and valve function

Pharmacological

Empirical therapy (native valve, acute presentation):

• Amoxicillin 2g IV QDS + gentamicin 1mg/kg IV BD (adjust for renal function)
• If penicillin-allergic: vancomycin 15-20mg/kg IV BD (target trough 15-20 mg/L) + gentamicin

Empirical therapy (prosthetic valve):

• Vancomycin + gentamicin + rifampicin 300-600mg PO BD

Organism-specific (common examples):

• Streptococcus viridans (penicillin-sensitive): benzylpenicillin 1.2g IV QDS for 4 weeks (± gentamicin for 2 weeks)
• S. aureus (MSSA): flucloxacillin 2g IV QDS for 4-6 weeks
• S. aureus (MRSA): vancomycin + rifampicin
• Enterococcus: amoxicillin 2g IV QDS + gentamicin for 4-6 weeks

Duration:

• Native valve: 4-6 weeks IV antibiotics
• Prosthetic valve: 6 weeks minimum
• Monitor gentamicin levels (trough <1 mg/L; peak 3-5 mg/L for synergistic dosing)

Surgical/Interventional

Indications for surgery:

• Heart failure from acute severe valve regurgitation (most common indication)
• Uncontrolled infection (persistent bacteraemia >7 days on appropriate therapy, abscess, fistula)
• Prevention of embolism (vegetation >10 mm with embolic event, or >15 mm despite antibiotics)
• Prosthetic valve endocarditis with severe dysfunction
• Fungal endocarditis (usually requires surgery)
• Pacemaker/ICD lead endocarditis (complete system extraction)

Referral Criteria

• All suspected IE: urgent referral to specialist IE team (cardiology + microbiology + cardiac surgery)
• Early surgical consultation is essential — ~50% of IE cases eventually require surgery
• Follow-up echocardiography at completion of therapy and at 3, 6, 12 months

• In-hospital mortality: ~20-30% overall
• Prosthetic valve endocarditis: mortality ~40%
• S. aureus IE: highest mortality (~40%)
• Viridans streptococcal IE: lower mortality (~10-15%)
• Right-sided IE (IVDU): generally better prognosis (~10% mortality)
• Risk factors for poor outcome: older age, prosthetic valve, S. aureus, heart failure, stroke, renal failure
• 1-year recurrence: ~5-10%
• Long-term: valve replacement may be needed even after successful antibiotic treatment

Peripheral Stigmata Summary

Modified Duke Criteria Summary