Infective endocarditis

Contents

Modified Duke Criteria

The Modified Duke Criteria (Li et al, 2000) classify the probability of IE:

Major Criteria

  1. Positive blood cultures:

    • Typical microorganism in two separate blood cultures (Strep viridans, Staph aureus, HACEK, Enterococcus without primary focus, Strep bovis)
    • Persistently positive blood cultures (≥2 positive cultures taken >12h apart, or ≥3 of 4 cultures if drawn >1h apart)
    • Single positive culture for Coxiella burnetii or phase 1 IgG titre >1:800

  2. Imaging evidence of endocardial involvement:

    • Echocardiographic vegetation, abscess, pseudoaneurysm, intracardiac fistula, or valvular perforation
    • New partial dehiscence of prosthetic valve
    • New valvular regurgitation (worsening of pre-existing murmur is insufficient)
    • Positive ¹⁸F-FDG PET/CT or cardiac CT (added in ESC 2023 modified criteria)

Minor Criteria

  1. Predisposing cardiac condition or IVDU
  2. Fever >38°C
  3. Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhage, Janeway lesions (non-tender macular lesions on palms/soles)
  4. Immunological phenomena: glomerulonephritis, Osler's nodes (painful, raised lesions on finger/toe pads), Roth spots (retinal haemorrhages with pale centres), positive rheumatoid factor
  5. Microbiological evidence not meeting major criteria (blood culture positive for organism consistent with IE but not qualifying under major criteria)

Classification

Category Criteria
Definite IE 2 major; OR 1 major + 3 minor; OR 5 minor (OR pathological criteria)
Possible IE 1 major + 1 minor; OR 3 minor
Rejected Alternative diagnosis, symptoms resolve <4 days on antibiotics, or pathology shows no IE

Microbiology — Organisms by Clinical Setting

Setting Most Likely Organisms
Native valve, community-acquired Streptococcus viridans group (dental source), Enterococcus faecalis (GI/GU), Staphylococcus aureus
Native valve, hospital-acquired / CVC-related Staphylococcus aureus, coagulase-negative Staphylococcus
Prosthetic valve, early (<12 months) Coagulase-negative Staphylococcus, S. aureus, gram-negative bacilli, fungi
Prosthetic valve, late (>12 months) Similar to native valve community-acquired pattern
IVDU — right-sided (tricuspid) Staphylococcus aureus (most common), Pseudomonas aeruginosa, Candida species
IVDU — left-sided S. aureus, Streptococci, Enterococcus
Culture-negative IE HACEK organisms (see below), Coxiella burnetii (Q fever), Bartonella spp., prior antibiotic treatment masking culture

HACEK Organisms

Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae: slow-growing fastidious gram-negative rods; dental/respiratory source; culture-negative with standard 5-day incubation; require extended culture (≥14 days) or PCR on valve tissue; usually respond to third-generation cephalosporins.

Culture-Negative Endocarditis

Causes: prior antibiotic treatment (most common); fastidious organisms (HACEK, Bartonella, Coxiella, Brucella, Tropheryma whipplei); fungal IE; technical issues. Strategies: serology for Coxiella (anti-phase 1 IgG), Bartonella; 16S rRNA PCR on blood; prolonged culture; liaise with microbiologists.

Investigations

Blood Cultures

  • Three sets from three separate venepuncture sites before antibiotics
  • Allow 10 mL per bottle (adult); adequate volume is critical
  • Each set should be drawn >1h apart if clinical stability allows
  • 10–30% of IE is culture-negative even with optimal technique

Echocardiography

  • Transthoracic echo (TTE): first-line; sensitivity 40–70% for vegetations; lower for small vegetations or prosthetic valves
  • Transoesophageal echo (TOE): sensitivity ~90%; better visualisation of aortic valve, prosthetic valves, posterior structures, small vegetations; indicated when TTE is non-diagnostic and suspicion remains high, or for all prosthetic valve IE
  • Repeat echo: if initial negative but suspicion remains — 5–7 days later

Additional Investigations

  • FBC (leucocytosis, anaemia of chronic disease, thrombocytopenia)
  • CRP, ESR (often markedly elevated)
  • Creatinine, urinalysis (haematuria, proteinuria from immune complex GN)
  • CT head: if neurological signs (embolic stroke, mycotic aneurysm)
  • CT thorax: septic pulmonary emboli in right-sided IE
  • Dental review: identify dental source
  • ¹⁸F-FDG PET/CT (in selected prosthetic valve IE, cardiac devices)

Empirical Antibiotic Therapy

Specific regimens depend on culture results, organism sensitivities, valve type, and patient factors. These are empirical frameworks:

Native Valve Endocarditis (UK practice; BCS/BSAC/ESC guidelines)

Community-acquired, no MRSA risk:

  • Amoxicillin 2 g IV 4-hourly + flucloxacillin 2 g IV 4-hourly + gentamicin 1 mg/kg 8-hourly

Penicillin-allergic or MRSA risk:

  • Vancomycin (target AUC/MIC 400–600 mg·h/L) + gentamicin

Duration: Streptococcal NVE: 2–4 weeks; Staphylococcal: 4–6 weeks; aminoglycosides: typically 2 weeks only (renal toxicity monitoring essential)

Prosthetic Valve Endocarditis

  • Vancomycin + gentamicin + rifampicin 300–600 mg 12-hourly
  • Rifampicin: do NOT start immediately; add after 5 days when bacteraemia has cleared (prevents emergence of rifampicin resistance)
  • Duration: ≥6 weeks

Right-Sided IE (IVDU, MRSA tricuspid endocarditis)

  • Daptomycin (preferred over vancomycin for S. aureus bacteraemia — superior bactericidal activity; check creatine kinase regularly; do not use in left-sided IE with pulmonary involvement as daptomycin is inactivated by surfactant)
  • OR vancomycin if no daptomycin available

Surgical Indications

The ESC (2023) classifies surgical urgency:

Urgent (within 24 hours) — Emergency surgery

  • Refractory pulmonary oedema or cardiogenic shock from acute severe AR or MR with LV/RV failure
  • Septic shock from valvular obstruction not responding to resuscitation

Early (within days) — Urgent surgery

  • Uncontrolled infection: perivalvular abscess, fistula, false aneurysm, enlarging vegetation despite appropriate antibiotics, fungi or highly resistant organisms
  • Embolic risk prevention: recurrent emboli despite adequate antibiotics; vegetation >10 mm with prior embolic episode; very large vegetation >15 mm (especially with other risk factors)
  • Heart failure from valvular dysfunction not meeting emergency criteria

Elective (during antibiotic course, scheduled timing)

  • Severe AR or MR with good patient condition
  • Prosthetic valve dysfunction

Specific Scenarios

  • Perivalvular abscess (most common site: aortic root with aortic valve IE): new PR prolongation, complete heart block, or sinus of Valsalva aneurysm on echo suggests aortic root abscess; high-risk feature requiring surgery
  • Neurological complication: IE-related stroke is not a contraindication to surgery; liaise with neurology/neurosurgery; generally wait 4 weeks after haemorrhagic stroke; proceed with non-haemorrhagic stroke if cardiac condition requires it (after neurosurgical assessment)

ICU-Specific Complications

Acute Valvular Regurgitation

  • Acute AR or MR from leaflet destruction or perforation → no time for cardiac remodelling
  • Acute AR: LV cannot accommodate sudden large regurgitant volume → flash pulmonary oedema; HR compensates but is limited; reduced diastolic BP → coronary ischaemia
  • Acute MR: LV ejects into non-compliant LA → flash APO
  • Haemodynamic support: vasodilators (↓ afterload), inodilators, IABP may help; definitive treatment is valve repair/replacement

Embolic Complications

  • Stroke: 20–40% of IE; most common in S. aureus and large vegetations; cardioembolic; treatment: anticoagulation NOT routinely recommended in native valve IE (risk of haemorrhagic transformation); aspirin has no proven benefit; surgical embolectomy not feasible; address with neurology
  • Splenic infarct: LUQ pain, fever; CT diagnosis; splenectomy if abscess, rupture, or persistent sepsis despite antibiotics
  • Renal infarct: flank pain, haematuria; CT diagnosis; conservative management usually
  • Septic pulmonary emboli: right-sided IE → bilateral nodular infiltrates on CXR/CT

Mycotic Aneurysms

  • Embolic seeding of arterial wall → aneurysm formation
  • Most dangerous: intracranial mycotic aneurysms → risk of subarachnoid/intracerebral haemorrhage
  • Screening: CT/MR angiography if any neurological symptoms; cerebral angiography if further concern
  • Treatment: antibiotics first; surgery/endovascular if enlarging, ruptured, or causing symptoms

Metastatic Infection

  • Vertebral osteomyelitis (especially S. aureus): back pain in IE patient — MRI spine
  • Septic arthritis, psoas abscess, epidural abscess

Viva Questions

1. What blood cultures should you take in suspected IE and when should antibiotics be started?

In suspected IE, obtain three sets of blood cultures from three different venepuncture sites before starting antibiotics. Allow at least 10 mL per bottle for adequate sensitivity. If clinical stability allows, draw sets at intervals (>1h apart) to differentiate true bacteraemia from contamination — three separate positive cultures with the same organism is strong evidence. However, in haemodynamically unstable or severely septic patients, the imperative to start antibiotics within 1 hour outweighs waiting — in these cases, take two or three sets rapidly (over 30–60 minutes) and start antibiotics immediately. Antibiotics should not be delayed to complete an optimal culture schedule if the patient is critically ill. Once initiated, serial repeat cultures should be taken (at 48–72h and again after changing regimen) to confirm clearance of bacteraemia — persistent bacteraemia after 3–7 days despite appropriate antibiotics suggests an undrained focus or complication (abscess, endovascular infection) requiring urgent investigation.

2. What are the signs of a perivalvular abscess and why does it change management?

A perivalvular abscess occurs when infection extends beyond the valve leaflets into the surrounding cardiac tissues — most commonly into the aortic root in aortic valve IE. It is a sign of locally uncontrolled infection and is one of the principal surgical indications. On ECG: new PR interval prolongation or complete heart block (infection has extended to the AV node or His bundle in the aortic root). On echo (TOE essential): perivalvular cavity, fistula, or false aneurysm — TOE is far more sensitive than TTE for this complication. Clinically: persistent fever, ongoing bacteraemia, or haemodynamic deterioration despite adequate antibiotics should raise suspicion. Importance: perivalvular extension cannot be sterilised with antibiotics alone — it requires surgical debridement, drainage, and valve replacement. Delay increases the risk of fistula formation (e.g. aorto-mitral curtain fistula), worsening heart block, and aortic root rupture. Early cardiothoracic surgical consultation and urgent surgery are indicated.

3. A patient with known IVDU is admitted with fever, tricuspid valve vegetation on echo, and bilateral nodular infiltrates on CXR. How do you manage them?

This presentation is typical of right-sided Staphylococcus aureus IE with septic pulmonary emboli — tricuspid valve is the most common site in IVDU-related IE; bacteraemia seeds the right side, and emboli go to the lungs. Management: (1) Blood cultures ×3 immediately, then antibiotics: empirical vancomycin or daptomycin (daptomycin is preferred for MRSA bacteraemia; note daptomycin should NOT be used if there is significant left-sided pulmonary involvement as it is inactivated by surfactant — check for left-sided involvement on echo); (2) Confirm MRSA status with nasal swab and cultures; switch to flucloxacillin if MSSA for superior bacteriostatic activity; (3) Duration: minimum 4–6 weeks for Staphylococcal native valve IE; right-sided MSSA IE sometimes treated with 2 weeks of IV followed by oral if no complications; (4) Surgical indications are less common in isolated right-sided IE (right heart can compensate better than left); surgery is indicated if vegetation >20 mm, septic pulmonary emboli causing respiratory failure, right heart failure, or persistent bacteraemia; (5) Address addiction medicine involvement, harm reduction, and ensure long-term plan to reduce re-infection risk.

4. What are the haemodynamic consequences of acute aortic regurgitation in IE and how does it differ from chronic AR?

Acute AR occurs when IE destroys the aortic valve leaflets or causes acute perivalvular abscess, producing sudden severe regurgitation into a normal-sized, non-compliant left ventricle. In contrast, chronic AR allows the LV to dilate and hypertrophy gradually, accommodating large regurgitant volumes before decompensation. In acute AR: the non-compliant LV cannot accommodate the large regurgitant volume → markedly elevated LV end-diastolic pressure → mitral valve closes prematurely (diastolic MR) → flash pulmonary oedema. The aorta cannot maintain adequate diastolic pressure (large regurgitant volume returns to LV) → reduced diastolic blood pressure → impaired coronary perfusion (which occurs in diastole) → myocardial ischaemia. The traditional pulse pressure widening and peripheral signs of AR (Corrigan's pulse, de Musset's sign) may be absent in acute AR because the haemodynamics are dominated by LV failure, not hyperdynamic circulation. Haemodynamic support: vasodilators (nitroprusside) to reduce afterload and forward flow; IABP can help (improves diastolic pressure and reduces afterload); inodilators if LV contractility is depressed. Definitive treatment is urgent valve surgery — no medical therapy is curative.