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Infective Endocarditis (IE): Detailed Guidelines

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1. Definition

• Goldman-Cecil Medicine, p. 700

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2. Epidemiology

• Annual incidence: approximately 13.8 per 100,000 globally (range 5.7-35.8/100,000 per 2019 GBD data)
• In the United States: 10,000-20,000 new cases per year (AHA estimates)
• In-hospital mortality: up to 22%; 5-year mortality: up to 40%
• Deaths due to IE increased 131% since 1990, with ~66,322 deaths and 1.7 million DALYs (2019 data)
• Male predominance historically, but female incidence is rising due to health care-associated IE and opioid epidemic
• The International Collaboration on Endocarditis (ICE) registry found contemporary IE is most often acute, predominantly Staphylococcus aureus, with mitral (41.1%) and aortic (37.6%) valves most involved
• Fuster and Hurst's The Heart, 15th ed., p. 45; Braunwald's Heart Disease, p. 824

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3. Microbiology

• Viridans group streptococci (VGS): subacute presentation, typically community-acquired; species include S. sanguis, oralis, salivarius, mutans, anginosus
• S. bovis/gallolyticus (associated with colon cancer - colonoscopy indicated)
• Streptococcus anginosus group: proclivity to form abscesses

• S. aureus: leading cause in developed countries; acute, destructive presentation; MRSA increasingly prevalent
• Coagulase-negative staphylococci (CoNS): mainly prosthetic valve endocarditis (PVE)

• E. faecalis and E. faecium: frequent in elderly, urinary tract-related bacteremia
• Require synergistic combination therapy

• Coxiella burnetii (Q fever) - phase I IgG ≥1:800 is major Duke criterion
• Bartonella spp. - cat scratch, homelessness
• Tropheryma whipplei, Brucella
• Braunwald's Heart Disease, p. 824; Harrison's 22nd ed.

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4. Pathogenesis

1. Endothelial damage - turbulent blood flow causes microscopic disruption of valve endothelium
2. Sterile thrombus formation - nonbacterial thrombotic endocarditis (NBTE) forms at site of injury (platelet-fibrin nidus)
3. Bacteremia - transient seeding from oral, GI, GU, or skin procedures/infections
4. Colonization - organisms adhere to the NBTE via surface adhesins (e.g., S. aureus fibronectin-binding proteins, clumping factors)
5. Vegetation formation - organisms multiply within the platelet-fibrin matrix, protected from host defenses and antibiotics

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5. Clinical Features

Symptoms

• Fever (most common - present in >90%)
• Constitutional: malaise, fatigue, night sweats, anorexia, weight loss
• Myalgias, arthralgias, back pain
• Symptoms of emboli: stroke, flank pain (renal infarct), chest pain (pulmonary embolism in right-sided IE)

Classic Physical Signs

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6. Diagnosis

Modified Duke Criteria (Revised 2000, Endorsed by AHA and ESC)

• Typical microorganisms (VGS, S. bovis, HACEK, S. aureus, community-acquired Enterococcus) from 2 separate blood cultures; OR
• Persistently positive blood cultures: ≥2 positive drawn >12 h apart, OR all 3, or majority of ≥4 separate cultures (with first and last drawn ≥1 h apart); OR
• Single positive blood culture for Coxiella burnetii or phase I IgG titer >1:800

• Vegetation, abscess, prosthetic valve dehiscence, new valvular regurgitation on echocardiography; OR
• New valvular regurgitation (worsening or change of pre-existing murmur is NOT sufficient)

1. Predisposing heart condition or injection drug use
2. Fever ≥38°C (100.4°F)
3. Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
5. Microbiological evidence: positive blood culture not meeting major criterion, or serological evidence of active infection with organism consistent with IE

• Definite IE: 2 major OR 1 major + 3 minor OR 5 minor criteria
• Possible IE: 1 major + 1 minor OR 3 minor criteria
• Rejected: Firm alternate diagnosis, resolution with ≤4 days antibiotics, no pathologic evidence at surgery/autopsy
• Fuster and Hurst's The Heart, 15th ed., p. 1005; Braunwald's Heart Disease

2023 ESC Guideline Updates to Diagnosis

NEW Class I, Level C recommendation: TEE is indicated in ALL patients with suspected IE, even when TTE is positive, EXCEPT in isolated right-sided native valve IE with good-quality TTE and unequivocal findings.

• Previously, TEE was Class IIa when TTE was positive; this is an upgrade.
• ESC 2023 Guidelines; PMC12779890

New Class I, Level B: Cardiac CTA recommended for patients with possible native valve endocarditis to detect (peri)valvular lesions when echocardiography is inconclusive.

• CTA is particularly useful for perivalvular extension, abscess, and pseudoaneurysm detection.

• ¹⁸F-FDG PET/CT: Useful for prosthetic valve IE (PVE) and CIED infections, detecting embolic events, and paravalvular lesions when echo is inconclusive (Class IIa)
• Radiolabeled leukocyte SPECT/CT: Alternative nuclear imaging for PVE

Blood Cultures

• At least 3 sets of blood cultures from separate venipunctures before starting antibiotics
• Each set: 1 aerobic + 1 anaerobic bottle
• Volume: 8-10 mL per bottle (adults)
• Do NOT delay cultures for repeat sampling if the patient is critically ill
• Special cultures for HACEK and fastidious organisms (Coxiella, Bartonella) require notification of microbiology

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7. The Endocarditis Team

• Infectious Disease specialist
• Cardiologist (ideally with IE expertise)
• Cardiac surgeon
• Neurologist (ESC 2023 now specifically recommends inclusion)
• Clinical microbiologist (ESC 2023)

"Every patient with IE should be managed in the inpatient setting of a medical center with experienced medical and surgical specialists... this team approach has resulted in improved outcomes."

• Braunwald's Heart Disease, p. 824

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8. Antibiotic Treatment

Streptococcal IE (Penicillin-susceptible VGS, MIC ≤0.12 μg/mL)

Staphylococcal IE (Native Valve)

• Nafcillin or oxacillin 12 g/day IV in 4-6 divided doses x 6 weeks (NVE)
• Cefazolin 6 g/day IV in 3 divided doses is acceptable alternative (with caution re: high-inoculum infection and beta-lactamase strains)
• Gentamicin and rifampin are NOT recommended routinely for MSSA NVE (no mortality benefit; increased nephrotoxicity)

• Vancomycin IV, targeting trough 15-20 μg/mL or AUC:MIC ratio >400 x 6 weeks
• Daptomycin 8-10 mg/kg/day IV for right-sided MRSA IE (non-inferior to vancomycin, fewer side effects)
• For MRSA with vancomycin MIC ≥2 μg/mL: consider daptomycin or alternative agents

• Vancomycin (or oxacillin for MSSA) + Rifampin 300 mg PO/IV q8h + Gentamicin 3 mg/kg/day
• Duration: minimum 6 weeks
• Rifampin added after 2 weeks of effective therapy (after bacteremia cleared) to prevent resistance

Enterococcal IE (Ampicillin-susceptible)

• Ampicillin + Ceftriaxone (preferred for E. faecalis; avoids aminoglycoside nephrotoxicity): 2 g q4h + 2 g q12h IV x 6 weeks
• Ampicillin + Gentamicin: Ampicillin 2 g IV q4h + Gentamicin 3 mg/kg/day IV x 4-6 weeks (monitor renal function)
• Vancomycin + Gentamicin for penicillin-allergic patients
• Vancomycin-resistant Enterococcus (VRE): requires early surgery consultation; linezolid or daptomycin-based regimens

HACEK organisms

• Ceftriaxone 2 g/day IV x 4 weeks (NVE) or 6 weeks (PVE)
• Ampicillin-sulbactam or fluoroquinolones as alternatives

Culture-negative IE (Empiric)

• Ampicillin-sulbactam + Gentamicin, OR
• Vancomycin + Gentamicin ± Ciprofloxacin (for HACEK coverage)

• Doxycycline + Hydroxychloroquine x ≥18 months
• Monitoring: phase I IgG titer should decline with treatment

• Doxycycline 100 mg PO/IV q12h + Gentamicin 3 mg/kg/day x 6 weeks
• Harrison's 22nd ed., Table 133-5; Goldman-Cecil Medicine

2023 ESC Update: Oral Antibiotic Step-Down Therapy

New recommendation (Class IIa): Transition from IV to oral antibiotic therapy may be considered in stable patients with native valve endocarditis due to viridans streptococci and select organisms, once clinical stabilization is achieved (typically after 7-10 days of IV therapy).

• Agents used: Oral amoxicillin in high doses or moxifloxacin
• NOT recommended for PVE, MRSA, fungi, or hemodynamically unstable patients
• Based on the POET trial (partial oral endocarditis treatment)
• ESC 2023 Guidelines; PMC12779872

Prophylaxis (AHA 2021 Updated Scientific Statement)

• Prosthetic cardiac valve or material
• Previous IE
• Congenital heart disease: unrepaired cyanotic CHD, repaired CHD with residual defects, repaired CHD with prosthetic material (within first 6 months)
• Cardiac transplant with valvulopathy
• NEW (2021): Ventricular assist devices and total artificial/implantable hearts

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9. Surgical Indications and Timing

1. Heart failure
2. Uncontrolled infection
3. Prevention of embolic events

Indications for Surgery - Native Valve IE

Indications for Surgery - Prosthetic Valve IE (PVE)

Surgical Timing (2023 ESC Major Update)

"Urgent surgery" is now redefined as within 3-5 days (previously classified more loosely). This change reflects evidence that early surgery reduces mortality and embolic risk. The Endocarditis Team decides timing, but surgery should not be delayed simply to await team assembly.

Surgery After Neurological Complications (2023 ESC Key Change)

UPGRADED to Class I, Level B: Perform surgery without delay after stroke (including ischemic stroke) IF heart failure, uncontrolled infection, abscess formation, or persistent high embolic risk is present, as long as:

• Coma is ABSENT
• Intracranial hemorrhage has been excluded by cranial CT/MRI

• Continue to delay cardiac surgery >1 month (maintained recommendation)
• NEW Class IIa: Consider urgent/emergency surgery in patients with intracranial hemorrhage and unstable clinical status (heart failure, uncontrolled infection) - case-by-case, frequent reassessment
• ESC 2023 Guidelines; PMC12779890

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10. Complications

• Stroke/TIA: most common (due to septic emboli, predominantly from left-sided vegetations)
• Mycotic aneurysm: MRI/MRA or CT angiography of entire neuraxis recommended
• Brain abscess
• Meningitis (especially S. aureus)

• Embolic renal infarction
• Immune-complex glomerulonephritis (especially VGS IE)
• Drug-induced nephrotoxicity (aminoglycosides, vancomycin)

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11. Special Situations

Right-Sided IE (PWID, CIED-associated)

• Most often S. aureus, tricuspid valve
• Presents with pulmonary septic emboli (pleuritic chest pain, hemoptysis, "cannonball" infiltrates on CXR)
• Right-sided regurgitation better tolerated than left-sided
• Surgery thresholds are higher; vegetation ≥20 mm, recurrent septic pulmonary emboli, persistent bacteremia, or difficult-to-treat organisms prompt surgery
• Valve repair preferred over replacement
• Class IIa: Avoid surgery when possible in active PWID (high re-infection rate)

Device-Related IE (CIED)

• Pacemakers, ICDs, CRT devices
• Complete device removal (transvenous or surgical) is preferred in documented CIED infection
• 6 weeks of antibiotics after device removal for bloodstream infection/pocket infection
• New implantation after treatment: ideally in a contralateral site

Pregnancy

• IE rare but high mortality for mother and fetus
• S. aureus and Streptococcus most common
• Avoid aminoglycosides (ototoxicity), fluoroquinolones, and tetracyclines
• Valve surgery carries high fetal mortality (~30%); reserve for refractory heart failure

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12. Summary of 2023 ESC Guideline Key Changes

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References

1. ESC 2023 Guidelines: 2023 European Society of Cardiology guidelines for the management of infective endocarditis - PMC12779890 (Dutch Working Group Implementation Review)
2. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 12th ed. (2022). Elsevier. ISBN: 9780323722193 - Chapter on Infective Endocarditis, pp. 824-850
3. Fuster and Hurst's The Heart, 15th ed. (2022). McGraw-Hill. ISBN: 9781264257560 - Chapter 33: Infective Endocarditis, pp. 999-1050
4. Harrison's Principles of Internal Medicine, 22nd ed. (2025). McGraw-Hill. ISBN: 9781265977061 - Chapter 133: Infective Endocarditis, pp. 1080-1095
5. Goldman-Cecil Medicine, International Edition (2024). ISBN: 9780323930345 - Chapter 61: Infective Endocarditis, p. 700
6. AHA 2021 Scientific Statement on IE Prevention: Baddour LM et al. (Braunwald's, p. 1232)
7. AHA 2015 Scientific Statement on IE Diagnosis/Management: Baddour LM, Wilson WR, Bayer AS, et al. Circulation. 2015;132(15):1435-1486
8. Duke Criteria (Modified 2000): Li JS et al. Clin Infect Dis. 2000;30:633-638

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2023 ESC Guidelines for the Management of Infective Endocarditis

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Overview: Five Pillars of Change

1. Antibiotic prophylaxis and prevention
2. Diagnostic criteria (updated Duke criteria + multimodality imaging)
3. Antibiotic therapy (including oral step-down)
4. Surgical indications and timing
5. Endocarditis Team and patient-centred care

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1. The Endocarditis Team - Upgraded to Class I

What Changed

Team Composition

• Cardiologist (with IE expertise)
• Cardiac surgeon
• Infectious disease specialist
• Neurologist (newly formalized)
• Clinical microbiologist (newly formalized)
• Imaging specialists (echocardiographer, nuclear medicine physician, radiologist)
• Additional specialists as needed: neurosurgeon, rheumatologist, nephrologist

Heart Valve Centres vs. Referring Centres

• Heart Valve Centre: Manages complicated IE, has on-site cardiac surgery, full multidisciplinary team
• Referring Centre: Can manage uncomplicated IE, but MUST maintain early and regular contact with a Heart Valve Centre

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2. Prevention - Most Novel Section vs. 2015

2A. Antibiotic Prophylaxis for Dental Procedures

General prevention measures (oral hygiene, skin hygiene) are recommended for all individuals at high and intermediate risk of IE. (Class I, Level C)

1. Patients with any prosthetic cardiac valve (surgical or transcatheter, including TAVI)
2. Patients with previous infective endocarditis
3. Patients with unrepaired cyanotic CHD
4. Patients with surgically corrected CHD with residual defects (palliative shunts, conduits, or other prostheses)
5. Patients with CHD repaired with prosthetic material within first 6 months after procedure
6. Patients with cardiac transplant and valvulopathy

• Dental extractions
• Oral surgery
• Procedures requiring manipulation of the gingival or periapical region of teeth

Systemic antibiotic prophylaxis may be considered for highest-risk patients undergoing invasive diagnostic or therapeutic procedures of the respiratory, GI, GU tract, skin, or musculoskeletal systems. (Class IIb, Level C)

2B. Prevention in Cardiac Procedures (New Emphasis)

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3. Diagnosis - Updated ESC Criteria (Major Change)

3A. Updated 2023 ESC Diagnostic Criteria (Modification of Duke Criteria)

MAJOR CRITERIA

(a) Typical microorganisms from 2 separate blood cultures:

• Oral streptococci
• Streptococcus gallolyticus (formerly S. bovis)
• HACEK group
• Staphylococcus aureus
• Enterococcus faecalis (NEW - regardless of acquisition source)

(b) Persistently positive blood cultures:

• ≥2 positive cultures drawn >12 h apart, OR
• All 3 or majority of ≥4 separate cultures (first and last ≥1 h apart)

(c) Single positive blood culture or serology for:

• Coxiella burnetii (phase I IgG >1:800)
• Bartonella species (IgG >1:800 by enzyme immunoassay - EIA now specifically included)

• Echocardiography: vegetation, abscess, pseudoaneurysm, intracardiac fistula, valvular perforation/aneurysm, new partial dehiscence of prosthetic valve
• NEW: Abnormal activity around prosthetic valve implanted >3 months ago detected by ¹⁸F-FDG PET/CT or radiolabelled leukocyte SPECT/CT
• NEW: Definite paravalvular lesions by cardiac CT

• Direct intraoperative identification of endocarditis by the cardiac surgeon (Class IIa, Level C)
• This is a brand-new major criterion not present in 2015 or 2000 criteria

MINOR CRITERIA (refined, not fundamentally changed)

1. Predisposing condition (heart disease, IVDU, prosthetic material)
2. Fever ≥38°C
3. Vascular phenomena: arterial emboli, septic pulmonary infarcts, Janeway lesions, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages
4. Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
5. Microbiological evidence not meeting major criterion
6. NEW minor criterion: Imaging findings consistent with IE by echocardiography (not meeting major criterion)

• Definite IE: 2 major OR 1 major + 3 minor OR 5 minor
• Possible IE: 1 major + 1 minor OR 3 minor
• Rejected: Firm alternate diagnosis, resolution within ≤4 days of antibiotics, no pathological evidence

3B. Echocardiography - TEE Upgraded to Class I Across the Board

• S. aureus bacteraemia: echo always indicated (maintained)
• NEW (Class IIa): Consider echo in patients with E. faecalis bacteraemia and some Streptococcus spp. bacteraemia

3C. Cardiac CT (Computed Tomography Angiography)

3D. Nuclear Imaging (¹⁸F-FDG PET/CT and WBC SPECT/CT)

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4. Antibiotic Therapy

4A. General Principles

• All antibiotic regimens for IE require bactericidal activity to penetrate avascular vegetations
• Parenteral (IV) therapy remains the default route for IE
• Minimum blood cultures (3 sets from separate venepunctures) before starting antibiotics
• Therapy duration: 4-6 weeks (depending on organism and native vs. prosthetic valve)

4B. NEW: Oral Step-Down (Switch) Therapy - POET Trial-Based

Transition from IV to oral antibiotic therapy may be considered in clinically stable patients with left-sided NVE (native valve endocarditis) caused by susceptible streptococci, E. faecalis, S. aureus, or coagulase-negative staphylococci, after at least 10 days of IV therapy (or 7 days post-surgery), once clinical and biochemical criteria are met. (Class IIa)

• Clinical stability (afebrile ≥48 h, no signs of heart failure, no embolic events)
• Sterile blood cultures on IV therapy
• No cardiac complications requiring surgery
• No concern about GI absorption (no nausea, vomiting, GI disease)
• Patient adherence is assured
• TEE performed before switch to confirm stable/resolving lesions (new Class I, Level B)

• Prosthetic valve endocarditis (PVE)
• CIED-related IE
• Fungal IE
• Hemodynamic instability
• Dialysis-dependent renal failure
• Ongoing embolic events

• Streptococcal/E. faecalis: Amoxicillin 1g q6-8h + Clavulanate, or Moxifloxacin-based regimen
• Staphylococci (MSSA): Amoxicillin-clavulanate + ciprofloxacin (POET regimen)
• MRSA: No established oral regimen; IV vancomycin/daptomycin continued

4C. Standard Antibiotic Regimens

• Penicillin G 12-18 MU/day IV q4h × 4 weeks, OR
• Ceftriaxone 2 g IV/IM once daily × 4 weeks
• Short course (2 weeks): Penicillin G + Gentamicin 3 mg/kg/day (uncomplicated NVE only)
• PVE: 6-week regimen

• MSSA: Nafcillin/Oxacillin 12 g/day IV in 6 divided doses × 4-6 weeks OR Cefazolin 6 g/day IV
• MRSA: Vancomycin 15-20 mg/kg IV q8-12h (target AUC/MIC >400) × 6 weeks
• Daptomycin 8-10 mg/kg/day IV is an alternative for right-sided and MSSA NVE
• Gentamicin and rifampin: NOT recommended routinely for NVE (toxicity, no survival benefit)

• Ampicillin 2g IV q4h + Ceftriaxone 2g IV q12h × 6 weeks (preferred - avoids aminoglycoside nephrotoxicity)
• Alternative: Ampicillin + Gentamicin × 4-6 weeks (monitor renal function closely)
• Vancomycin-resistant Enterococcus (VRE): early surgery referral; linezolid or daptomycin-based

• Vancomycin (or oxacillin for MSSA) + Rifampin 300 mg PO/IV q8h + Gentamicin × 6 weeks minimum
• Add rifampin only after 2 weeks of effective therapy (after bacteraemia cleared)

• Native valve, community-acquired: Ampicillin + Flucloxacillin/Oxacillin + Gentamicin
• Nosocomial/Healthcare-associated: Vancomycin + Gentamicin
• PVE: Vancomycin + Rifampin + Gentamicin

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5. Surgical Indications and Timing - Redefined

5A. New Surgical Timing Definitions (Major Change)

The shortening of "urgent" from <7 days to 3-5 days emphasises that delays should be avoided once surgical indication is established - particularly critical in non-referral centres.

5B. Three Main Surgical Indications

I. Heart Failure

II. Uncontrolled Infection

III. Prevention of Embolic Events

5C. Surgery After Neurological Complications (Key Upgrade)

5D. Right-Sided IE Surgery

5E. Early PVE Surgery (New Recommendation)

NEW: Surgery is recommended for early PVE (<6 months) caused by Staphylococcus spp. or gram-negative organisms (Class I - the Dutch Working Group modified this to Class IIa given limited evidence, but the ESC recommends Class I)

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6. CIED (Cardiac Implantable Electronic Device) IE

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7. Transcatheter Valve IE (TAVI-Associated IE)

• TAVI-IE incidence: 0.5-3% per patient-year
• Most common organisms: S. aureus, Enterococcus, CoNS
• Modified Duke criteria have lower sensitivity for TAVI-IE (echo appearance differs from surgical prostheses)
• Multimodality imaging (CT, PET) is particularly important for TAVI-IE diagnosis
• Redo-TAVI or valve-in-valve procedures may be considered in inoperable patients
• Pre-TAVI: Antibiotic prophylaxis covering skin flora + Enterococcus + S. aureus (IIa, Level C)
• Pre-TAVI: S. aureus nasal screening and decolonisation recommended (I, Level B)

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8. Neurological Complications - Comprehensive Algorithm

• Stroke must prompt immediate CT/MRI of brain to exclude haemorrhage before surgery decisions
• Cerebral MRI (especially DWI sequences) recommended in all IE to detect silent cerebral emboli, microabscesses
• Whole-body CT or PET/CT to detect extracranial emboli (splenic, renal, vertebral)
• In cerebral aneurysms (mycotic): if intervention needed, endovascular approach preferred over open surgery
• Epicardial pacemaker should be considered in patients requiring surgery for IE who develop complete AV block with any of: pre-existing conduction abnormality, S. aureus infection, aortic root abscess, tricuspid valve involvement, or prior valve surgery

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9. Outpatient/OPAT and Patient-Centred Care (New Emphasis)

• Patient is clinically stable, afebrile, with sterile blood cultures on IV therapy
• No cardiac or non-cardiac complications requiring hospitalisation
• Appropriate IV access (PICC line)
• Reliable patient with good follow-up infrastructure

• Shared decision-making involving patient and family
• Palliative/supportive approach discussed explicitly for patients not candidates for surgery
• Psychosocial support for patients with substance use disorder (PWID) - harm reduction, addiction medicine
• Quality of life and patient preferences incorporated into surgical decisions

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10. Follow-Up After IE - Two Phases

• Blood cultures at completion of antibiotic treatment
• Clinical examination and CRP/ESR at 1, 3, 6, and 12 months
• Echocardiography at 1, 3, 6, and 12 months
• Risk of recurrence: 2-9% (includes relapse and reinfection)

• Annual clinical and echocardiographic follow-up
• Dental hygiene reinforced at every visit
• Patient education regarding IE risk, prophylaxis, and when to seek medical attention

• Relapse: Same organism recurring <6 months - treatment failure; search for persistent focus; evaluate for surgery
• Reinfection: Different organism, usually >6 months after initial episode

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Summary Table: 2023 ESC Key New and Upgraded Recommendations

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References

1. Delgado V, et al. 2023 ESC Guidelines for the management of endocarditis. European Heart Journal 2023;44(39):3948-4042. DOI: 10.1093/eurheartj/ehad193 (Primary Guideline Document)
2. Imazio M. The 2023 new European guidelines on infective endocarditis: main novelties and implications for clinical practice. J Cardiovasc Med 2024. PMID: 38916201 - PMC11365601
3. de Waha S, Desch S, Tilz R. ESC guidelines 2023 on the management of endocarditis: What is new? Herz 2024 Feb. PMID: 38092975
4. Peijster AJL, et al. 2023 ESC guidelines for IE: Statement of endorsement by the NVVC. Neth Heart J 2026 Jan. PMID: 41410976 / PMID: 41410977
5. Borger MA, et al. Key priorities for implementation of the 2023 ESC IE Guidelines in low-resource settings. Eur Heart J Qual Care Clin Outcomes 2025. PMID: 40152919
6. Fowler VG, et al. The 2023 Duke-ISCVID Criteria for Infective Endocarditis. Clin Infect Dis 2023;77(4):518-526 (parallel update to diagnostic criteria)
7. Iversen K, Ihlemann N, et al. Partial oral versus intravenous antibiotic treatment of endocarditis (POET Trial). N Engl J Med 2019;380:415-424 (basis for oral step-down recommendation)
8. Braunwald's Heart Disease, 12th ed. (2022), Chapter 80G - cited in Braunwald's Heart Disease, ISBN 9780323722193
9. Fuster and Hurst's The Heart, 15th ed. (2022), Chapter 33 - cited in Fuster/Hurst ISBN 9781264257560
10. Harrison's Principles of Internal Medicine, 22nd ed. (2025), Chapter 133 - cited in Harrison's ISBN 9781265977061