Chapter 133: Infective Endocarditis¶
Chapter 133 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Infective endocarditis (IE) is a heterogeneous disease with variable clinical presentations, ranging from acute to subacute courses.
- The 2023 Duke-ISCVID criteria emphasize microbiologic, imaging, and clinical findings for diagnosing IE, with specific thresholds for blood cultures and echocardiography.
- Staphylococcus aureus is the most common bacterial cause of IE in developed countries, while enterococci and viridans streptococci are prominent in native valve endocarditis (NVE).
- Antibiotic therapy for IE requires prolonged durations (4–6 weeks) and often includes combinations of β -lactams, aminoglycosides, and vancomycin for resistant organisms.
- Cardiac surgery is indicated for severe complications like paravalvular abscesses, valve dysfunction, or persistent bacteremia despite optimal antimicrobial therapy.
1. DEFINITION & OVERVIEW¶
Infective endocarditis (IE) is an infection of the heart valves or intracardiac devices, characterized by the formation of vegetations composed of platelets, fibrin, microorganisms, and inflammatory cells. It can occur in native valves (NVE) or prosthetic valves (PVE), with distinct microbiologic and clinical features.
Table 133-1: Organisms Causing Major Clinical Forms of Infective Endocarditis (IE)¶
| Organism(s) | Native-Valve IE (%) | Prosthetic-Valve IE (%) | TAVR PVE (%) | CIED-IE (%) |
|---|---|---|---|---|
| Streptococci | 40 | 13 | 18 | 2 |
| Enterococci | 9 | 16 | 24 | 4 |
| Staphylococcus aureus | 28 | 52 | 23 | 36 |
| Coagulase-negative staphylococci | 5 | 11 | 20 | 41 |
| Fastidious gram-negative coccobacilli (HACEK group) | 3 | — | — | — |
| Gram-negative bacilli | 1 | 1 | 1 | 6 |
| Candida spp. | <1 | 1 | 1 | 2 |
| Polymicrobial/miscell aneous | 3 | 3 | 8 | 2 |
| Culture-negative | 9 | 3 | 5 | 6 |
1.1 Clinical Spectrum¶
IE spans a continuum from acute (febrile, rapidly progressive) to subacute (chronic, indolent) presentations. Acute IE is often caused by S. aureus, while subacute IE is more common with viridans streptococci, enterococci, or HACEK organisms.
1.2 Complications¶
Common complications include embolic events, valvular dysfunction, heart failure, and systemic spread (e.g., septic emboli, abscesses). CIED-IE may involve device-related infections or lead pocket infections.
2. EPIDEMIOLOGY¶
The incidence of IE is estimated at 15 cases per 100,000 population annually in developed countries, with rising trends linked to opioid use disorder and injection drug use. Mortality varies: 2–75% depending on etiology and comorbidities. Risk factors include age >60, immunocompromise, and prosthetic valves.
2.1 Demographics¶
Age-adjusted mortality declined in ≥ 55 years but increased in 25–44 years. PWID account for 35–60% of tricuspid valve IE cases.
2.2 Risk Factors¶
Injection drug use, degenerative valve disease, prosthetic valves, and immunocompromised states (e.g., HIV, transplant recipients) are major risk factors.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
IE is caused by bacteria, fungi, or atypical organisms. Pathogenesis involves endothelial injury, platelet-fibrin thrombus formation, and microbial adherence via MSCRAMMs. Prosthetic valves and CIEDs increase susceptibility.
Table 133-2: Clinical and Laboratory Features of Infective Endocarditis¶
| Feature | Frequency (%) |
|---|---|
| Fever | 80–90 |
| Chills and sweats | 40–75 |
| Anorexia, weight loss, malaise | 25–50 |
| Myalgias, arthralgias | 15–30 |
| Back pain | 7–15 |
| Heart murmur | 80–85 |
| New/worsened regurgitant murmur | 20–50 |
| Arterial emboli | 20–50 |
| Splenomegaly | 15–50 |
| Clubbing | 10–20 |
| Neurologic manifestations | 20–40 |
| Peripheral manifestations (Osler’s nodes, Janeway lesions, Roth’s spots) | 2–15 |
3.1 Common Pathogens¶
Staphylococcus aureus (most common), enterococci, viridans streptococci, HACEK organisms, and fungi (e.g., Candida) are primary causative agents. Atypical pathogens like Bartonella, Coxiella, and Mycobacterium chimaera are associated with culture-negative IE.
3.2 Molecular Mechanisms¶
Microbial adhesion to damaged endothelium is mediated by MSCRAMMs (e.g., fibronectin-binding proteins in S. aureus). Biofilm formation on prosthetic surfaces enhances resistance to antibiotics.
4. CLINICAL FEATURES¶
Symptoms include fever, fatigue, and constitutional signs. Local signs include heart murmurs, embolic events, and valvular dysfunction. Complications include embolic stroke, abscesses, and systemic spread.
4.1 Constitutional Symptoms¶
Fever (80–90%), chills, weight loss, and malaise are common. Subacute IE presents with low-grade fever (<39.4°C).
4.2 Cardiac Findings¶
New or worsening murmurs, valvular regurgitation, and signs of heart failure (e.g., pulmonary edema) are frequent. Embolic events (e.g., Janeway lesions) occur in 15–35% of cases.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include systemic lupus erythematosus, antiphospholipid syndrome, and other infections (e.g., tuberculosis, fungal infections). Culture-negative IE must be distinguished from non-infectious conditions like marantic endocarditis.
5.1 Non-Infectious Mimics¶
Marantic endocarditis (uninfected vegetations in malignancy or chronic disease) and antiphospholipid syndrome can mimic IE.
5.2 Atypical Pathogens¶
Coxiella burnetii, Bartonella species, and Tropheryma whipplei are associated with culture-negative IE, often presenting with indolent courses.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis requires microbiologic, imaging, and clinical criteria. Blood cultures, echocardiography, and PCR are essential. The Duke-ISCVID criteria guide diagnosis.
Table 133-3: Modified Duke Criteria for Infective Endocarditis¶
| Major Criteria | Minor Criteria |
|---|---|
| Positive blood culture (typical/ntypical organisms) | Predisposition (prior IE, drug use, prosthetic valve) |
| Positive PCR for C. burnetti, Bartonella, T. whipplei | Fever (>38°C) |
| Echocardiography showing vegetation/abscess | Vascular phenomena (emboli, mycotic aneurysm) |
| FDG-PET/CT with abnormal metabolic activity | Immunologic phenomena (Osler’s nodes, Roth’s spots) |
| Major Criteria | Minor Criteria |
|---|---|
| Surgical evidence of IE | Microbiologic evidence (positive blood cultures) |
6.1 Diagnostic Criteria¶
Definite IE requires microbiologic (positive blood cultures) or imaging (vegetations on echocardiography) evidence. Possible IE is defined by 1 major + 1 minor criterion.
6.2 Imaging Techniques¶
Transesophageal echocardiography (TEE) is preferred for detecting vegetations, abscesses, and paravalvular complications. FDG-PET/CT is useful for assessing metabolic activity in prosthetic valves.
7. MANAGEMENT & TREATMENT¶
Antimicrobial therapy is the cornerstone, with duration and combinations tailored to the pathogen. Surgical intervention is indicated for complications like abscesses, valve dysfunction, or persistent bacteremia.
Table 133-5: Antibiotic Treatment for Infective Endocarditis¶
| Organism(s) | Drug (Dose, Duration) | Comments |
|---|---|---|
| Streptococci (penicillin-susceptible) | Penicillin G (2–3 mU IV q4h for 4 weeks) | Use ampicillin or amoxicillin if penicillin unavailable |
| Streptococci (relatively penicillin-resistant) | Penicillin G (4 mU IV q4h) + gentamicin (3 mg/kg daily) | Preferred for penicillin MIC >0.12 mg/mL |
| Enterococci | Ampicillin (2 g IV q4h) + gentamicin (3 mg/kg daily) | 6 weeks for PVE; 4–6 weeks for NVE |
| MRSA (prosthetic valve) | Vancomycin (15 mg/kg IV q12h) + rifampin (300 mg PO q8h) | 6–8 weeks; daptomycin is an alternative |
| C. burnetii | Doxycycline (100 mg PO q12h) + hydroxychloroquine (200 mg PO q8h) | 18–24 months for native/prosthetic valve |
7.1 Antibiotic Regimens¶
Streptococcal IE: Penicillin + gentamicin (6 weeks). Enterococcal IE: Ampicillin + gentamicin (6 weeks). MRSA: Vancomycin or daptomycin. CIED-IE: Vancomycin + rifampin.
7.2 Surgical Indications¶
Surgery is required for paravalvular abscesses, severe valve dysfunction, persistent bacteremia, or complications like embolism. TAVR-PVE often requires surgical intervention.
8. PROGNOSIS & COMPLICATIONS¶
Overall survival rates are 80–85% in developed countries, but vary by pathogen and comorbidities. Mortality is highest in PVE (40–50%) and TAVR-PVE (35–50%). Complications include embolism, heart failure, and device-related infections.
8.1 Survival Outcomes¶
NVE caused by viridans streptococci or enterococci has 85–90% survival. S. aureus NVE has 55–70% survival, while PVE has 40–50% mortality within 2 months of valve replacement.
8.2 Long-Term Risks¶
Recurrence rates are 10–20% for NVE and 6–15% for PVE. CIED-IE requires device removal and long-term antimicrobial suppression.
9. SPECIAL CONSIDERATIONS¶
Pregnancy, pediatric, and elderly populations require tailored approaches. PWID and OUD patients need aggressive antibiotic therapy and substance use management.
9.1 Pregnancy¶
Antimicrobial therapy must avoid teratogens (e.g., gentamicin). Prophylaxis for dental procedures is recommended for high-risk patients.
9.2 PWID and OUD¶
PWID account for 35–60% of tricuspid IE. OUD is a major risk factor; treatment must include medication-assisted therapy (MAT) and prolonged antibiotic courses.
10. KEY POINTS & CLINICAL PEARLS¶
- Use TEE for definitive diagnosis of IE, especially in prosthetic valves.
- Antibiotic duration for NVE is 4–6 weeks; PVE requires 6 weeks.
- Surgical intervention is indicated for paravalvular abscesses, valve dysfunction, or persistent bacteremia.
- CIED-IE requires device removal and antimicrobial therapy targeting the causative organism.
- Prophylaxis is recommended for high-risk patients undergoing dental procedures (e.g., those with prosthetic valves).