7.4 Infective Endocarditis
Key Takeaways
- Definite endocarditis requires two major modified Duke criteria, or one major plus three minor, or five minor criteria.
- Streptococcus gallolyticus (formerly Streptococcus bovis) endocarditis mandates colonoscopy because of its strong association with colorectal neoplasia.
- Surgery is indicated for heart failure from valve destruction, uncontrolled infection or abscess, and recurrent embolism with a vegetation larger than 10 mm.
5. Infective Endocarditis (IE)
Microbiology
- Staphylococcus aureus (~35–40%): Most common cause overall in high-income nations. Characterized by acute, rapidly destructive presentations on previously normal native valves. Predominant organism in intravenous drug users (IVDU), classically affecting the tricuspid valve and presenting with septic pulmonary infarcts, cavitation, and pleuritic chest pain without peripheral stigmata.
- Viridans Group Streptococci (S. sanguinis, S. mitis, S. mutans) (~20–25%): Cause subacute native valve endocarditis on abnormal or diseased valves (rheumatic, BAV, prolapse). Typically follow dental procedures or poor oral hygiene.
- Streptococcus gallolyticus (formerly S. bovis): Strongly associated with underlying colorectal carcinoma or premalignant villous adenomas. Isolation mandates immediate full colonoscopy.
- Enterococcus faecalis / faecium: Associated with older men following transurethral resection of the prostate (TURP), cystoscopy, or gastrointestinal instrumentation.
- Coagulase-Negative Staphylococci (S. epidermidis): Major cause of early prosthetic valve endocarditis (PVE within 12 months of valve surgery) and central line infections.
- HACEK Group: Fastidious gram-negative bacilli (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella). Indolent presentation; often culture-negative on routine standard media, requiring extended incubation.
- Culture-Negative IE: Coxiella burnetii (Q fever; diagnose via Phase I IgG serology), Bartonella henselae/quintana, Chlamydia, Brucella, Tropheryma whipplei. Non-bacterial thrombotic endocarditis (Marantic) occurs in advanced malignancy; Libman-Sacks endocarditis occurs in systemic lupus erythematosus.
Modified Duke Criteria for Diagnosis
Definitive diagnosis requires: 2 Major criteria, OR 1 Major + 3 Minor criteria, OR 5 Minor criteria.
| Major Criteria | Minor Criteria |
|---|---|
| 1. Positive Blood Cultures for IE:<br>• Typical microorganisms from 2 separate blood cultures (S. aureus, Viridans streptococci, S. gallolyticus, Enterococci, HACEK), OR<br>• Persistently positive cultures: drawn >12 hours apart, or all of 3 (or majority of >=4) cultures positive, OR<br>• Single positive culture for Coxiella burnetii (or Phase I IgG antibody titre >1:800) | 1. Predisposition: Pre-existing high-risk cardiac lesion (prosthetic valve, prior IE, cyanotic congenital disease) or intravenous drug use |
| 2. Evidence of Endocardial Involvement:<br>• Echocardiography positive for IE: oscillating intracardiac mass (vegetation) on valve or supporting structures, perivalvular abscess, pseudoaneurysm, or new partial dehiscence of prosthetic valve, OR<br>• New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) | 2. Fever: Core temperature >= 38.0°C |
| 3. Vascular Phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysms, intracranial haemorrhage, conjunctival haemorrhages, and Janeway lesions (non-tender, erythematous macules on palms/soles from septic microemboli) | |
| 4. Immunologic Phenomena: Glomerulonephritis, Osler nodes (painful, tender violaceous nodules on the pads of fingers/toes due to immune complex deposition), Roth spots (oval retinal haemorrhages with pale, white centres), and positive serum rheumatoid factor | |
| 5. Microbiological Evidence: Positive blood culture not meeting major criteria, or serological evidence of active infection with compatible organism |
Antibiotic Protocols & Indications for Urgent Surgery
- Blood Culture Sampling: Draw 3 sets of blood cultures from separate venepuncture sites with at least 30 minutes between draws before initiating antibiotics (unless patient is in septic shock).
- Empirical Regimens (NICE / ESC):
- Native Valve, Subacute Presentation: IV Ampicillin/Amoxicillin (2 g 4-hourly) + IV Gentamicin (1 mg/kg BD) OR IV Ceftriaxone monotherapy.
- Native Valve, Acute Severe Sepsis / MRSA Risk: IV Vancomycin (15–20 mg/kg BD with trough monitoring) + IV Gentamicin.
- Prosthetic Valve Endocarditis (PVE): IV Vancomycin + IV Gentamicin + Oral Rifampicin (penetrates biofilms on foreign material; started 3–5 days after vancomycin to avoid rapid emergence of resistance).
- Indications for Urgent Cardiac Surgery in IE:
- Heart Failure: Severe acute aortic or mitral regurgitation causing pulmonary oedema or cardiogenic shock (leading surgical indication).
- Uncontrolled Infection: Perivalvular extension (aortic root abscess manifested on ECG by a new prolonged PR interval / first-degree heart block), persistent fever and positive cultures >7–10 days despite appropriate bactericidal therapy, or infection with resistant organisms (fungi, MDR Gram-negatives).
- Prevention of Embolism: Large mobile vegetations (>10 mm) following one or more systemic embolic episodes, or very large isolated vegetations (>15 mm).
Antimicrobial Therapy
Treatment is prolonged, intravenous and organism-directed, and the duration depends on whether the valve is native or prosthetic.
| Situation | Typical UK empirical regimen |
|---|---|
| Native valve, indolent presentation | Amoxicillin (with or without gentamicin) |
| Native valve, severe sepsis or suspected Staphylococcus aureus | Flucloxacillin, or vancomycin if MRSA risk or penicillin allergy |
| Prosthetic valve | Vancomycin plus gentamicin plus rifampicin |
Native valve infection is usually treated for 4-6 weeks; prosthetic valve endocarditis requires at least 6 weeks, with rifampicin added for its activity against organisms in biofilm. Rifampicin is not started until bacteraemia is clearing, and it is a potent CYP450 inducer that will destabilise warfarin.
Culture-Negative Endocarditis
Around 5-10% of cases are blood-culture negative, most often because antibiotics were given before cultures were taken — the single commonest and most avoidable cause. Genuine fastidious organisms to consider are Coxiella burnetii (Q fever, in farmers and abattoir workers), Bartonella species (homelessness, body lice, cat exposure), Brucella, Tropheryma whipplei and the HACEK group, which now usually do grow in modern automated systems. Serology and 16S ribosomal RNA PCR on excised valve tissue are the diagnostic routes.
Non-Infective and Special Situations
Non-bacterial thrombotic (marantic) endocarditis produces sterile vegetations in advanced malignancy, especially adenocarcinoma, and presents with embolic stroke rather than fever. Libman-Sacks endocarditis occurs in systemic lupus erythematosus and antiphospholipid syndrome. Right-sided endocarditis, typically tricuspid Staphylococcus aureus disease in people who inject drugs, causes septic pulmonary emboli with multiple cavitating nodules on chest imaging rather than systemic embolism, and murmurs are frequently absent.
Prophylaxis: the UK Position
UK practice diverges from some international guidance and is examined for exactly that reason. NICE does not recommend routine antibiotic prophylaxis against infective endocarditis for people undergoing dental or other interventional procedures. Emphasis is instead placed on maintaining good oral health, on advising at-risk patients about the symptoms of endocarditis and the need to seek early advice, and on investigating unexplained fever in patients with prosthetic valves or previous endocarditis promptly with three sets of blood cultures from separate sites before antibiotics.
A 64-year-old farmer presents with a 6-week history of low-grade fever, malaise, night sweats, and 4 kg weight loss. He has a history of a bicuspid aortic valve. Examination reveals a temperature of 38.2°C, blood pressure of 128/72 mmHg, a soft early diastolic murmur at the left sternal border, and splinter haemorrhages in several fingernails. Transoesophageal echocardiography reveals an 8 mm oscillating vegetation on the aortic valve with mild aortic regurgitation. Three sets of peripheral blood cultures drawn 12 hours apart all grow Streptococcus gallolyticus (formerly Streptococcus bovis). Following the initiation of targeted intravenous antibiotic therapy, which of the following investigations is essential in the comprehensive management of this patient?
A 48-year-old woman with a history of intravenous drug use is admitted with high fevers, rigors, and dyspnoea. On physical examination, her temperature is 38.9°C, pulse is 110 bpm, and blood pressure is 100/60 mmHg. Examination of the hands reveals several non-tender, erythematous macules across the palmar aspects of both hands and soles of her feet. Examination of the eyes reveals oval retinal haemorrhages with pale, pale-white centres. A pansystolic murmur is heard at the lower left sternal edge that increases in intensity on inspiration. Which of the following correctly pairs these two clinical findings with their respective category under the Modified Duke Criteria for infective endocarditis?