Infective Endocarditis (IE) - A Detailed Overview

1. Definition and Historical Context

Definition: Infective endocarditis (IE) is an infection of the endocardial surface of the heart. This can involve heart valves, the mural endocardium, or foreign bodies within the heart.
Historical Note: The gross autopsy findings of IE were first described in 1674 by Lazaire Riviere.

2. Epidemiology of Infective Endocarditis

Rarity: IE is considered a rare disease.
Incidence: In 2019, the incidence of IE was reported as 13.8 cases per 100,000 individuals per month.
Mortality Rate: The intrahospital mortality rate for IE ranges from 15-30 percent.
Increasing Risk: The number of individuals at risk for IE is on the rise due to factors such as longer survival rates, increased use of implantable cardiac devices, and prostheses.

3. Pathogenesis of Infective Endocarditis

The development of IE involves a complex interplay of predisposing factors, pathogen entry, and the host's immune response, as illustrated by a Venn diagram showing the intersection of "Predisposing risk factors," "Pathogens entering the bloodstream," and "A person's immune response."

Initial Endothelial Damage: The process often begins with an endothelial defect on heart valves, foreign bodies, or large vessels.
Non-Bacterial Thrombus Formation: A non-bacterial thrombus forms at the site of the endothelial defect.
Immune Response and Exposure: Endocardial damage exposes the extracellular matrix layer and phospholipids of the outer endothelial cell membrane. This triggers immune cells to produce antiphospholipid antibodies.
Pathogen Colonization and Progression: Pathogenic microorganisms entering the bloodstream settle in these damaged areas, colonize them, and penetrate deeper into the endocardium. This leads to a progressive inflammatory process, maturation of bacterial vegetations, local abscess formation, and ultimately, valve dysfunction.
Vegetation Dissemination: Particles from these vegetations can distribute throughout the bloodstream, leading to embolic events.
Circulating Immune Complexes: The titers of circulating immune complexes increase, targeting both autoantigens and microorganism antigens.
Detailed Pathophysiological Diagram (Lerche CJ et al., 2021):
- Endothelial Layer and Subendothelial Parenchyma: The diagram depicts the endothelial layer lining the blood lumen and the underlying subendothelial parenchyma.
- Flow and Shear Stress: Blood flow and shear stress are indicated, influencing the interaction of blood components with the infected valve vegetation.
- Infected Valve Vegetation: This central structure is shown to contain circulating bacteria.
- Cytokines in Valve Vegetations: Elevated levels of IL-1B, IL-6, IL-8 (KC), IL-17, G-CSF, IFN-y, and VEGF are noted, while IL-10 is decreased.
- Hypoxic Zone: A hypoxic (O₂ depleted) zone is present within the vegetation.
- Cellular and Molecular Components:
  - Platelets: Activated platelets are shown adhering.
  - Neutrophils: Degraded and degranulated neutrophils, along with Neutrophil Extracellular Traps (NETs), are present.
  - Monocytes: Monocytes are involved.
  - Endothelial Cells: Both normal and activated endothelial cells contribute to the process.
  - Fibrin, Fibrinogen, Proteins, and Collagen: These components form the structural matrix of the vegetation.
  - Bacteria: Specific bacteria like *S. aureus* (depicted in black/red) are shown, including persisters and small-colony variants.
  - Thrombin, Tissue Factor, Activated Complement Components: These factors (C3a & C5a) contribute to coagulation and inflammation.
- Cytokines in Serum: Elevated levels of IL-1B, IL-6, IL-8 (KC), VEGF, G-CSF, TNF-a, and IL-10, IL-17 are observed in the serum.
- Septic Thrombus Dissemination: The diagram illustrates the potential for septic thrombi to disseminate from the vegetation into the bloodstream.

4. Etiology of Infective Endocarditis

IE is primarily caused by bacterial or fungal infections. Viruses are explicitly stated as not being a cause of IE.

Streptococci:
- Oral streptococci: *Str. viridans* groups (e.g., *S. sanguis*, *S. oralis* (mitis), *S. salivarius*, *S. mutans*, *S. intermedius*, *S. anginosus*, *S. constellatus*).
- Others.
Staphylococci:
- *S. Aureus*.
- Coagulase-negative staphylococci (e.g., *S. epidermidis*, *S. lugdunensis*).
Enterococci:
- *Enterococcus faecalis*.
HACEK group (Gram-negative bacteria):
- *Haemophilus*, *Actinobacillus*, *Cardiobacterium*, *Eikenella*, *Kingella padermės*.
Other Pathogens:
- Anaerobic Gram-negative bacteria.
- Fungi.
- Slow-growing microorganisms.

5. IE Diagnostics Overview

The diagnosis of IE relies on a combination of three main pillars:

Clinical Suspicion/Expression: Based on patient symptoms and risk factors.
Microbiological Diagnosis: Identification of the causative pathogen.
Heart Damage Confirmed by Imaging Studies: Visualization of cardiac lesions.

6. IE Suspicion in Different Clinical Situations and Non-Cardiac Risk Factors

6.1. Clinical Situations Suggesting IE

Newly diagnosed or progressive heart failure.
Cerebrovascular accident (e.g., embolism, hemorrhage, abscess).
Cardiac device infection.
Fever of unknown origin, with no other identified cause.
Fever accompanied by a new heart murmur.
Known heart disease, especially with prosthetic valves, mitral valve prolapse, or rheumatic defects.
Previous bacteremia.
New conduction disorders.
Embolism of unknown origin.
Cardiogenic or septic shock.
Recurrent pulmonary infarctions or abscesses.

6.2. Non-Cardiac Risk Factors for IE

Presence of a central venous catheter.
Intravenous drug users.
Immunosuppression.
Recent dental or surgical procedures.
Recent hospitalization.
Haemodialysis.

7. Clinical Features of Infective Endocarditis

IE manifests with a variety of general, cardiac, and non-cardiac symptoms and signs.

7.1. General Symptoms and Signs

Fever and Chills:
- Occur in 80-95% of cases, presenting as subfebrile or febrile temperatures.
- May be absent in older patients, those treated with antibiotics, individuals with diabetes, or immunosuppressed persons.
Intoxication:
- Symptoms depend on the causative agent, disease course, and stage.
- Common signs include weakness, general malaise, weight loss, sweating, lack of appetite, nausea, headache, and joint pain.

7.2. Cardiac Symptoms and Signs

Dyspnea: Symptoms of heart failure due to valve leakage or obstruction.
Chest Pain:
- Myocardial ischemia in severe aortic valve regurgitation (AVR).
- Embolic myocardial infarction (MI).
- Pericardial pain due to spread of infection to the annulus and pericardium.
- Pleural chest pain due to septic embolization from the tricuspid valve (TV) to the lungs, leading to pneumonia.
Murmurs:
- Daily auscultation is crucial.
- Murmurs may not be present in IE involving intracardiac devices or in annular abscesses until valve perforation, rupture of chordae tendineae, or prosthesis dehiscence occurs.
ECG Changes:
- A-V node damage and A-V conduction disorders (I-III block) due to the spread of infection to the aortic valve annulus and abscess formation.

7.3. Non-Cardiac Symptoms and Complications

Non-cardiac manifestations are often due to embolic events or immunological phenomena.

Embolic Complications: The size of vegetations correlates with the frequency of embolic events. These can affect:
- Neurologic system
- Vascular system
- Internal organs (kidney, spleen, lungs, etc.)
- Skeletal system
- Rheumatologic system
- Ocular system
- Skin
Immunologic Complications: Manifestations related to the body's immune response.

7.3.1. Septic Embolism in IE

A diagram illustrating septic embolism distribution shows various organs affected and their approximate prevalence:

Nervous System:
- Brain: 48-65%
- Retina: Very rare
- Spinal cord: Very rare
Lungs: ~14%
Coronary Vessels: ~6%
Liver: 3-11%
Spleen: 19-32%
Kidneys: 6-14%
Mesenteric: ~3%
Bones & Joints: ~11%
Arterial: 3-6%
Extremities & Musculoskeletal: ~30% & ~44% respectively.

7.3.2. IE Neurologic Complications

Symptomatic Complications: Occur in about 35% of cases.
- Most Common: Stroke, transient ischemic attack (TIA).
- Less Common: Hemorrhage, meningitis, abscess, encephalopathy, infectious aneurysms.
Silent Complications: Detected in up to 80% of cases.
- Ischemia, microhemorrhages.
Suspicion: IE should be suspected in stroke patients with fever of unknown origin, especially those with known valvular disease. Blood cultures should be taken before antibiotic treatment.
Imaging Examples: CT scans show evidence of neurological complications, such as an infarct in the brain (top image) and a hemorrhagic lesion (bottom image).

7.3.3. Septic Embolism in Heart, Abdominal Organs, Limbs, and Lungs

Septic emboli can affect various organs, leading to specific complications:

Spleen:
- Infarctions, abscesses, rupture are common.
- Can be asymptomatic.
- An image shows a splenic infarct (Blužnies infarktai).
Other Abdominal Organs:
- Kidney, mesenteric arteries can be affected.
Heart: Embolic events can affect the heart itself. An image shows an embolic occlusion of the left anterior descending (LAD) artery (Embolinė PTŠ okliuzija) and its appearance after angioplasty (Po atliktos ekstrinės VA angioplastikos).
Embolism to the Limbs: Can cause acute ischemia.
- Surgical treatment and microbiological diagnosis of the embolus are important.
- An image shows acute occlusion of leg arteries (Ūmi kojų arterijų okliuzija).
Lungs:
- Septic pulmonary infarctions are common in patients with right-sided IE.
- An image shows pulmonary abscesses (Plaučių abscesai).

7.3.4. Infectious (Mycotic) Aneurysms (IA)

Location: Can form in any artery.
Angiographic Detection: An aneurysm detected angiographically, especially with an existing infection, and showing angiographic signs such as multiple or distal locations, changes in size, or new appearance, is indicative of IA.
Imaging Examples: Images show angiographic views of mycotic aneurysms, including a renal artery aneurysm (indicated by an arrow) and other vascular lesions.

7.3.5. Kidney Damage / Acute Renal Failure

Causes of Damage:
- Immune complex and vasculitis-associated glomerulonephritis.
- Renal infarctions.
- Hemodynamic instability.
- Nephrotoxicity from drugs and contrast agents.
Visual Representation: A diagram illustrates a healthy kidney.

7.3.6. Rheumatological Symptoms

These symptoms are associated with the infectious-immunological pathogenesis of IE.

Myalgia and back pain.
Arthralgia (joint pain).
Less often, manifestations like rheumatic polymyalgia and cutaneous leukocytoclastic vasculitis.
Positive immunological laboratory tests.

7.3.7. Musculoskeletal Complications

These include septic arthritis, osteomyelitis, psoitis, and spondylodiscitis.

Spondylodiscitis: Occurs in about 2-10% of cases (both asymptomatic and symptomatic).
IE Detection in Spondylodiscitis: IE is detected in approximately 20-30% of patients with spondylodiscitis.
Recommendation: Transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) is recommended to exclude IE in patients with spondylodiscitis and/or septic arthritis when blood cultures contain typical IE pathogens.

7.3.8. Skin Signs in IE Patients

Specific dermatological manifestations can indicate IE:

Janeway's Erythema: Rough macules found on the palms. Images show red, irregular macules on the palms and soles.
Multiple Osler's Nodules: Tender, erythematous nodules typically found on the fingers. Images show tender erythematous nodules on the fingers and toes.
Splinter Hemorrhages: Linear hemorrhages under the nails, resembling splinters. Images show splinter hemorrhages under the fingernails.

7.3.9. Eye Symptoms in IE Sufferers

Ocular manifestations can also occur:

Roth's Spot: Retinal hemorrhages with a pale center. These can change dynamically over time (e.g., initial image, after 3 days, after 3 months). Often asymptomatic. Images show retinal hemorrhages with pale centers.
Conjunctival Hemorrhages: Bleeding in the conjunctiva of the eye. An image shows conjunctival hemorrhages.
Endophthalmitis: Inflammation of the internal structures of the eye. An image shows endophthalmitis.

8. Laboratory Tests for IE

Laboratory investigations are crucial for microbiological diagnosis, assessing inflammatory markers, sepsis severity, and organ damage.

8.1. Microbiological Diagnostics

Blood Cultures:
- Necessity: Culture before antibiotic administration is self-evident.
- Procedure: At least three blood cultures of 10 ml each should be taken at 30-minute intervals and incubated in both aerobic and anaerobic atmospheres.
- Sampling Site: Samples should be obtained from a peripheral vein using aseptic techniques, rather than from a central venous catheter.
- Timing: There is no rationale for delaying blood sampling to coincide with fever peaks; nearly all blood cultures are positive during bacteremia.
Blood Culture-Negative Infective Endocarditis:
- Causes: Can result from previous antibiotic administration, infection with fungi or fastidious bacteria (especially obligatory intracellular bacteria).
- Management: Withdrawal of antibiotics and repeating blood cultures may be necessary in stable patients with subacute symptoms.
- Alternative Diagnostics: Serological tests and histological/microbiological diagnosis of emboli from surgical materials are important.

8.2. Inflammatory Markers, Sepsis Severity, and Organ Damage Assessment

Complete Blood Count: Frequently reveals anemia and leukocytosis.
Markers of Inflammation and Sepsis: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, and lactates.
Minor IE Criteria Search: Rheumatoid factor.
Organ Damage and Risk Assessment: Lactates, creatinine, bilirubin, troponin, and natriuretic peptides are used to assess organ damage and risk.
Urinalysis.

9. Imaging Techniques for IE

Imaging plays a vital role in IE diagnosis and the detection of complications.

9.1. Echocardiography (TTE / TEE)

For Diagnostics:
- TTE (Transthoracic Echocardiography): First-choice test for suspected IE.
- TEE (Transesophageal Echocardiography): Used when TTE is negative or inconclusive, or if a prosthetic valve or pacemaker is present.
For Treatment Monitoring:
- TTE/TEE may be repeated after 5-7 days if the initial test is negative but IE suspicion persists.
For Treatment Completion / Complication Detection:
- TTE/TEE is repeated when complications are suspected (e.g., new murmur, embolism, persistent fever, heart failure, AV block).

9.1.1. Echocardiographic Findings

The table below defines characteristic cardiac lesions detected by echocardiography:

Leaflet Thickening: Diffuse, more or less regular increase in thickness of one or more leaflets, without vegetations.
Vegetations: Oscillating or non-oscillating intracardiac echogenic mass attached to a valve, other endocardial structures (chordae, chamber walls), or implanted intracardiac material.
- Location: Most often attached to the valve surface on the lower pressure side of the cavity.
- Embolism Risk: Large vegetations carry a higher risk of embolism or valve obstruction (especially prosthetic).
- Important Characteristics: Localization, size, morphology, quantity, mobility, and relationship with other structures are crucial for assessment.
- Imaging Examples: Multiple echocardiographic images display vegetations of varying sizes and locations on heart valves.
Abscess: Non-homogeneous echogenic or echolucent perivalvular thickening.
- Imaging Examples: Echocardiographic images show perivalvular thickening, some with color Doppler flow indicating communication.
Pseudoaneurysm: Pulsatile perivalvular echo-free space, with color Doppler flow detected.
- Imaging Examples: Echocardiographic images show perivalvular echo-free spaces with color Doppler flow.
Perforation: Leaflet tissue defect through which flow is observed with color Doppler images.
- Imaging Examples: Echocardiographic images demonstrate leaflet perforations with visible flow.
Fistula: Color Doppler communication between two neighboring cavities through a perforation.
Valve Aneurysm: Saccular swelling of the valve tissue.
Prosthetic Valve Dehiscence: Paravalvular regurgitation identified in color Doppler, with or without rocking motion of the prosthesis.
- Imaging Examples: Echocardiographic images show prosthetic valve dehiscence with paravalvular regurgitation.

9.2. Radiologic Tests

CT (Computed Tomography) / CTA (CT Angiography) in IE Diagnostics:
- Cardiac Complications: Detects IE cardiac complications, including native and prosthetic valve issues (fistulas, abscesses, pseudoaneurysms).
- Remote Lesions: Identifies peripheral embolization and mycotic aneurysms.
- Neurological Complications: Useful for detecting neurological complications.
- Primary Focus of Infection: Helps search for the primary focus of infection (e.g., oncology, or other infection sources if IE is ruled out).
- Reclassification: Can lead to IE reclassification upon identification of additional findings (minor IE criteria).
- Imaging Example: A CT scan shows a cross-section of the heart, highlighting potential areas of infection or damage.
MRI (Magnetic Resonance Imaging) in IE Diagnostics:
- Sensitivity: MRI has higher sensitivity than CT for detecting neurological complications.
- Neurological Findings: Identifies hemorrhages, abscesses, and mycotic aneurysms, which can influence clinical decisions.
- Spinal Injury: Detects spinal injury, such as spondylodiscitis and osteomyelitis.
- Reclassification: Can lead to IE reclassification upon identification of additional findings (minor IE criteria).
Nuclear Studies in IE Diagnostics ([18F]FDG-PET/CT, WBC SPECT):
- Prosthetic Valve IE (PVE): Indicated in suspected PVE when TEE is incompletely informative, to identify metabolic and anatomical changes.
- Remote Lesions and Bacteremia Source: Useful for detecting remote lesions (septic emboli) and identifying the source of bacteremia.
- FDG Uptake in PVE vs. Non-Infected PV (Roque A et al., 2022): A series of PET/CT images illustrates FDG uptake patterns.
  - PVE (Prosthetic Valve Endocarditis):
    - Focal/Multifocal: Shows intense, localized FDG uptake around the prosthetic valve (VUI 0.67).
    - Diffuse + Heterogeneous: Shows more widespread and varied FDG uptake around the valve (VUI 0.51).
  - Non-PVE (Non-Infected Prosthetic Valve):
    - Diffuse + Homogeneous: Shows mild, uniform FDG uptake, likely physiological (VUI 0.35).
    - Absent: Shows no significant FDG uptake around the valve (VUI 0.36).

10. 2023 ESC Modified IE Criteria

These criteria are used for the definitive diagnosis of IE, categorized into major and minor criteria.

10.1. Major Criteria

Blood Cultures Positive for IE:
1. Typical microorganisms consistent with IE from two separate blood cultures: Oral streptococci, *Streptococcus gallolyticus* (formerly *S. bovis*), HACEK group, *S. aureus*, *E. faecalis*.
2. Microorganisms consistent with IE from continuously positive blood cultures:
  1. ≥2 positive blood cultures of blood samples drawn >12 hours apart.
  2. All of 3 or a majority of ≥4 separate cultures of blood (with first and last samples drawn ≥1 hour apart).
3. Single positive blood culture for *C. burnetii* or phase I IgG antibody titre >1:800.
Imaging Positive for IE: Valvular, perivalvular/periprosthetic, and foreign material anatomic and metabolic lesions characteristic of IE detected by any of the following imaging techniques:
- Echocardiography (TTE and TEE).
- Cardiac CT.
- [18F]-FDG-PET/CT(A).
- WBC SPECT/CT.

10.2. Minor Criteria

Predisposing Conditions: Predisposing heart condition at high or intermediate risk of IE or in people who inject drugs (PWIDs).
Fever: Defined as temperature >38°C.
Embolic Vascular Dissemination (including those asymptomatic detected by imaging only):
1. Major systemic and pulmonary emboli/infarcts and abscesses.
2. Haematogenous osteoarticular septic complications (i.e., spondylodiscitis).
3. Mycotic aneurysms.
4. Intracranial ischaemic/haemorrhagic lesions.
5. Conjunctival haemorrhages.
6. Janeway's lesions.
Immunological Phenomena:
1. Glomerulonephritis.
2. Osler nodes and Roth spots.
3. Rheumatoid factor.
Microbiological Evidence:
1. Positive blood culture but does not meet a major criterion as noted above.
2. Serological evidence of active infection with organism consistent with IE.

11. IE Classification (at admission and during follow-up)

Definite IE:
- 2 major criteria.
- 1 major criterion and at least 3 minor criteria.
- 5 minor criteria.
Possible IE:
- 1 major criterion and 1 or 2 minor criteria.
- 3-4 minor criteria.
Rejected IE:
- Does not meet criteria for definite or possible IE at admission, with or without a firm alternative diagnosis.

12. Signs of Poor Prognosis in IE

Several factors indicate a poor prognosis in IE patients:

12.1. Patient Characteristics

Older age.
Prosthetic valve IE.
Hemodialysis.
Unsuitable for surgery (frailty).
Diabetes mellitus.
High Charlson comorbidity index.

12.2. Clinical Complications of IE

Heart failure.
Cerebral complications.
Septic shock.
Renal failure.

12.3. Echocardiographic Findings

Perianular complications.
Left heart IE.
Vegetation size >10 mm.
Large left heart valve regurgitation.
Reduced left ventricular ejection fraction (LV EF).
Pulmonary hypertension.
Prosthetic valve dysfunction.
Severe diastolic dysfunction or echocardiographic evidence of high LV diastolic pressure.

12.4. Microbiological Features

*S. aureus* infection.
Fungal infection.
Non-HACEK Gram-negative bacilli infection.
Persistent bacteremia.

13. Treatment of Infective Endocarditis

Treatment for IE is multifaceted, involving antimicrobial therapy, surgical intervention, symptomatic management, and prevention.

13.1. Principles of Antibacterial Treatment

Goals: Eradication of pathogens and removal of infected tissues.
Drug Type: Combinations of bactericidal drugs are typically used.
Administration: Most antibiotics are administered parenterally.
Duration of Treatment:
- Native valve IE (NVIE): 4 weeks (sometimes 2 weeks for uncomplicated cases with good renal function).
- Prosthetic valve IE (PVIE): ≥ 6 weeks.
- After prosthetic heart valve replacement, treatment continues according to native valve IE duration.
- Duration is calculated from the first day of effective treatment (negative culture if initial was positive).

13.2. Empirical Therapy

Prompt Initiation: Treatment should be started promptly.
Blood Cultures: Three sets of blood cultures should be drawn at 30-minute intervals before initiating antibiotics.
Regimens:
- Native Valve Endocarditis (NVE) and Late PVE Regimens: Should cover staphylococci, streptococci, and enterococci.
- Early PVE or Healthcare-Associated IE Regimens: Should cover methicillin-resistant staphylococci, enterococci, and ideally, non-HACEK Gram-negative pathogens.
Transition to Targeted Therapy: Empirical treatment should be changed to targeted therapy once the organism is identified (within 24-48 hours).

13.2.1. Empirical Therapy Regimens (Table Summary)

Community-acquired NVE or late PVE (<12 months post-surgery):
- Ampicillin (12 g/d i.v. in 4–6 doses) in combination with Ceftriaxone (4 g/d i.v. or i.m. in 2 doses) or (Flu)cloxacillin (12 g/d i.v. in 4–6 doses) and Gentamicin (3 mg/kg/d i.v. or i.m. in 1 dose).
Early PVE (<12 months post-surgery) or nosocomial and non-nosocomial healthcare-associated IE:
- Vancomycin (30 mg/kg/d i.v. in 2 doses) or Daptomycin (10 mg/kg/d i.v. in 1 dose) combined with Gentamicin (3 mg/kg/d i.v. or i.m. in 1 dose) and Rifampin (900–1200 mg i.v. or p.o in 2 or 3 doses).
Allergy to Beta-Lactam Antibiotics: Change to Cefazolin or Vancomycin.

13.3. Antibiotic Treatment by Pathogen

13.3.1. Oral Streptococci and Streptococcus gallolyticus Group

NVIE (4 weeks) / PVIE (6 weeks):
- Penicillin G: 12-18 million units i.v. in 4–6 doses or continuous infusion.
- Ceftriaxone: 2 g/d i.v. or i.m. in 1 dose.
- Amoxicillin: 100-200 mg/kg/d i.v. in 4–6 doses.
- A 2-week treatment period may be considered for uncomplicated NVIE with good renal function, optionally with Gentamicin (3 mg/kg/d i.v. in 1 dose).
Allergy to Beta-Lactam Antibiotics: NVIE - Vancomycin; PVIE - Vancomycin with Gentamicin.

13.3.2. Staphylococcus spp. (Methicillin-Susceptible)

NVIE (4-6 weeks): (Flu)cloxacillin (12 g/d i.v. in 4–6 doses) or Cefazolin (6 g/d i.v. in 3 doses).
PVIE (at least 6 weeks): All three prescribed: (Flu)cloxacillin (12 g/d i.v. in 4–6 doses) or Cefazolin (6 g/d i.v. in 3 doses), Rifampin (900 mg/d i.v. or p.o in 3 doses), and Gentamicin (3 mg/kg/d i.v. or i.m. in 1 dose, only for 2 weeks).
Allergy to Beta-Lactam Antibiotics: Change to Cefazolin.

13.3.3. Enterococcus spp.

NVIE and PVIE (6 weeks): Ampicillin (12 g/d i.v. in 4–6 doses) or Amoxicillin (12 g/d i.v. in 4–6 doses) + Ceftriaxone (4 g/d i.v. in 2 doses) or Gentamicin (3 mg/kg/d i.v. or i.m. in 1 dose, only for 2 weeks).

13.4. Antithrombotic Treatment in Patients with IE

Contraindications: Antiplatelets and anticoagulants are contraindicated in the presence of major bleeding, including intracranial bleeding.
Individual Assessment: Patients with IE often use antithrombotic drugs for other conditions (e.g., ischemic heart disease (IHD), atrial fibrillation (AF), implanted prostheses). Their continuation is assessed individually based on the disease course, complications, and indications for surgery.
Thrombolysis: Thrombolysis is contraindicated in stroke with IE.

13.5. Surgical IE Treatment

Surgical intervention is a critical component of IE management, particularly for specific complications.

13.5.1. Main Indications for Surgical Treatment

A diagram illustrates three main indications:

Heart Failure: Symptoms include dilated pupils, pale/gray/cyanotic skin, dyspnea, orthopnea, crackles/wheeze, cough, anxiety, falling O2 saturation, confusion, jugular vein distention, infarct, fatigue, S3 gallop, tachycardia, enlarged spleen/liver, decreased urine output, weak pulse, cool/moist skin, nausea/vomiting, ascites, dependent/pitting edema.
Uncontrolled Infection: Indicated by persistent bacteremia or local abscesses.
Prevention of Systemic Embolism: Emboli can affect the brain (with secondary hemorrhage), ocular fundus (retinal infarction), skin (petechiae, clubbing), kidneys (infarcts), and spleen (mycotic aneurysms, infarct, splenomegaly).

13.5.2. Timing of Surgical Treatment

Emergency: Within 24 hours.
Urgent: Within 3-5 days.
Non-urgent: Within the same hospital admission.
Risk vs. Futility: High-risk but salvageable patients may not be offered life-saving operations due to perceived unacceptable risk. Determining when operative management is futile requires compassionate multidisciplinary insight and consideration of the patient's and family's wishes.

13.5.3. Indications for Surgery and Management of Main IE Complications

Heart Failure:
- Aortic valve (AV) or mitral valve (MV) IE (native or prosthetic) with severe acute regurgitation or obstruction causing:
  - Refractory pulmonary edema or cardiogenic shock.
  - Heart failure symptoms or echocardiographic signs of poor hemodynamic tolerance.
Uncontrolled Infection:
- Locally uncontrolled infection (abscess, pseudoaneurysm, fistula, enlarging vegetation).
- Infection caused by fungi or a multiresistant organism.
- Persistently positive blood cultures >1 week, despite appropriate antibiotic therapy.
- PVIE caused by *S. aureus* or non-HACEK Gram-negative bacteria.
Prevention of Systemic Embolism:
- AV or MV IE (native or prosthetic) with vegetations >10 mm after ≥1 embolic episode or other indication for surgery.
- May be considered when vegetations >10 mm without other indications for surgery.

14. Right-Sided Infective Endocarditis (RSIE)

Prevalence: Accounts for about 5-10% of all IE cases.
Risk Factors: Congenital heart defects, long-term catheters, implanted electrical heart devices, immunosuppressive individuals, and intravenous drug users.
Most Common Pathogen: *S. aureus*.
Most Commonly Affected Valve: Tricuspid valve.
Predominant Symptoms: Fever, sepsis, lung damage, possible pulmonary hypertension due to septic emboli, and right heart failure.
Conservative Treatment: Approximately 90% of RSIE cases are treated conservatively.
Poor Prognosis Factors: RSIE associated with cardiac devices, immunosuppression, and fungal infection carries a very poor prognosis.
Surgical Treatment Recommendations:
- Dysfunction of the right ventricle (RV) due to severe acute tricuspid valve regurgitation (TVR) and resistance to diuretics.
- Persistent vegetations in the presence of respiratory failure requiring pulmonary ventilation after recurrent pulmonary emboli.
- Persistent TV vegetations (>20 mm) after repeated septic emboli to the lungs.
- Damage to the valves on the left side of the heart.
- Persistent bacteremia/sepsis after 1 week of optimal antibiotic therapy.
- Suctioning of large vegetations from the right atrium (RA) may be considered when the surgical risk is high.

15. IE Monitoring

Continuous monitoring is essential to assess treatment effectiveness and detect complications.

Dynamics of Symptoms and Signs: Regular assessment of clinical presentation.
Temperature Monitoring: Every 2 hours.
Inflammatory Markers: Monitoring of C-reactive protein (CRp) and erythrocyte sedimentation rate (ESR) dynamics.
Monitoring for Complications:
- Echocardiography (TTE and TEE).
- Electrocardiogram (ECG) for AV conduction abnormalities.
- Abdominal ultrasound, CT, and MRI.
Causes of Persistent Fever:
- Inadequate antibiotic therapy.
- Resistant microorganisms.
- Infected catheters.
- Locally uncontrolled infection.
- Embolic complications.
- Non-cardiac infection.
- Adverse reaction to antibiotic therapy.

16. IE Prevention

Prevention strategies target individuals at high and intermediate risk.

16.1. Individuals at High Risk of IE

Patients with previous IE.
Patients with implanted prosthetic valves or other implants:
- Surgically or transcatheter implanted prosthetic valves and any materials used for heart valve reconstruction.
- Patients with septal defects and left atrial appendage closure devices, vascular prostheses, vena cava filters during the first 6 months after implantation.
Patients with congenital heart disease:
- Untreated cyanotic heart disease, and individuals who have undergone surgery using prosthetic material, including valvular conduits or systemic-pulmonary shunts.
- After transcatheter closure of atrial or ventricular septal defect with devices or surgery with non-valvular prosthetic materials within the first 6 months after surgery.
Patients with ventricular assist devices as destination therapy.

16.2. Individuals at Intermediate Risk of IE

These individuals have a higher risk of IE compared to the background population.

Rheumatic heart disease.
Non-rheumatic degenerative valvular disease.
Congenital valve abnormalities, including bicuspid aortic valve.
Implanted electrical cardiac devices.
Hypertrophic cardiomyopathy.

For patients at intermediate risk of IE, antibiotic prophylaxis is not routinely recommended but may be considered on an individual basis. However, general prophylaxis is recommended for these patients.

16.3. General Prevention Measures for High and Intermediate Risk Patients

Encourage twice daily tooth cleaning and professional dental cleaning/follow-up (at least twice yearly for high-risk patients, yearly for others).
Strict cutaneous hygiene, including optimized treatment of chronic skin conditions.
Disinfection of wounds.
Curative antibiotics for any focus of bacterial infection.
No self-medication with antibiotics.
Strict infection control measures for any at-risk procedure.
Discouragement of piercing and tattooing.
Limitation of infusion catheters and invasive procedures; when possible, strict adherence to care bundles for central and peripheral cannulae.

16.4. IE Prevention When Performing Oral/Dental Procedures

The oral cavity is colonized by mixed flora, including oral streptococci.
The risk group for IE from dental procedures includes:
- Tooth extraction procedures.
- Oral surgical procedures (including periodontal surgery, implantation, and oral cavity biopsy).
- Dental procedures involving the gums or periapical area of the teeth.
Antibiotic Prophylaxis:
- Only recommended for patients at high risk of IE.
- May be considered in patients after heart transplantation.

16.4.1. Antibiotic Prophylaxis During High-Risk Dental Procedures (Table Summary)

Single dose 30-60 minutes before procedure:

No Allergy to Penicillin or Ampicillin:
- Amoxicillin: 2 g oral.
- Ampicillin: 2 g i/m or i/v.
- Cefazolin or Ceftriaxone: 1 g i/m or i/v.
Allergy to Penicillin or Ampicillin:
- Cefalexin (or other first- or second-generation oral cephalosporin): 2 g oral.
- Azithromycin or Clarithromycin: 500 mg oral.
- Doxycycline: 100 mg oral.
- Cefazolin or Ceftriaxone: 1 g i/m or i/v.
Important Note: Cephalosporins should not be used in individuals with a history of anaphylaxis, angioedema, or urticaria with penicillin or ampicillin.

Comprehensive Study Material on Infective Endocarditis (IE)

Comprehensive Study Material on Infective Endocarditis (IE)