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2023 ESC Guidelines for the Management of Endocarditis

Clinical Quick Reference — Diagnosis, Antimicrobial Therapy, Surgical Indications & Management

Published: European Heart Journal (2023), 44:3948–4042
Societies: ESC (European Society of Cardiology), endorsed by EACTS & EANM
DOI: 10.1093/eurheartj/ehad193
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What's New in 2023

This update reflects major advances in the diagnosis and management of infective endocarditis since the 2015 ESC Guidelines:

Diagnostic Innovations

Management Emphasis

Modified Duke Criteria (2023 ESC)

The revised criteria incorporate imaging advances and expanded pathogen recognition. Diagnosis requires definite, possible, or rejected classification based on major and minor criteria.

Major Criteria

1. Blood Cultures Positive for IE
  • Typical pathogens: oral streptococci, S. gallolyticus, S. aureus, HACEK group, E. faecalis
  • ≥2 positive blood cultures from separate draws OR ≥3 out of 4 separate cultures
  • Single positive blood culture for C. burnetii (phase I IgG antibody titre >1:800)
2. Imaging Positive for IE
  • Echocardiography (TTE or TOE): vegetations, perivalvular/prosthetic lesions
  • Cardiac CT, [18F]FDG-PET/CT, WBC SPECT/CT

Minor Criteria & Classification

Definite IE: 2 major criteria OR 1 major + ≥3 minor OR ≥5 minor

Possible IE: 1 major + 1–2 minor OR 3–4 minor

Rejected: Does not meet definite or possible IE criteria

Diagnosis Algorithm

Clinical Approach: Diagnosis rests on clinical suspicion supported by consistent microbiological data and imaging findings.

Diagnostic Steps

  1. Clinical Suspicion: Fever + predisposing factors (PWID, prosthetic valve, previous IE, CHD)
  2. Blood Cultures: ≥3 separate cultures BEFORE antibiotics; each 10 mL into aerobic/anaerobic bottles
  3. Echocardiography: TTE first-line; TOE if TTE quality poor or clinical suspicion remains
  4. Advanced Imaging: Cardiac CT, PET/CT for inconclusive cases or prosthetic valves
  5. Apply Duke Criteria: Classify as Definite, Possible, or Rejected

Key Timing Points

Microbiology & Causative Organisms

Most Common Pathogens (EURO-ENDO Registry)

Blood Culture-Negative IE (BCNIE)

Causes: Prior antibiotics, fastidious organisms (HACEK, Coxiella, Brucella, Legionella, Bartonella, Mycoplasma), fungi (Candida, Aspergillus).

Diagnostic Approach: Serology for Coxiella burnetii, Bartonella, Brucella; blood/tissue culture on specialized media; 16S rRNA/ITS sequencing; [18F]FDG-PET/CT.

Empiric Antibiotic Therapy

Recommended until culture results: Ceftriaxone 2g IV BD + Gentamicin 3 mg/kg IV daily + Ampicillin 2g IV QID (covers enterococci). Adjust within 24–48 hours based on organism identification and susceptibilities.

Antibiotic Regimens

Native Valve Endocarditis (NVE): Streptococci

Penicillin-Susceptible: Penicillin G 12–18 MU IV daily in 4–6 doses for 4 weeks OR Ceftriaxone 2g IV daily for 4 weeks ± gentamicin 3 mg/kg IV daily for 2 weeks.
Penicillin-Resistant: Penicillin G 24 MU IV daily for 4 weeks + gentamicin 3 mg/kg IV daily for 2 weeks OR Ceftriaxone 2g IV daily for 4 weeks + gentamicin.

Native Valve Endocarditis: Staphylococcus aureus

MSSA (Standard): Flucloxacillin 12g/day IV in 4–6 doses for 4–6 weeks OR Cefazolin 6g/day IV in 3 doses for 4–6 weeks ± gentamicin 3 mg/kg IV daily for first 3–5 days.
MRSA: Vancomycin 30–60 mg/kg IV daily (target trough 15–20 µg/mL) for 4–6 weeks + gentamicin 3 mg/kg IV daily for 2 weeks + rifampicin 900 mg/day in 3 divided doses.

Native Valve Endocarditis: Enterococcus

Beta-Lactam Susceptible: Ampicillin 12g/day IV in 4–6 doses for 6 weeks + gentamicin 3 mg/kg IV daily for 2 weeks.
Beta-Lactam Resistant: Vancomycin 30–60 mg/kg IV daily + gentamicin 3 mg/kg IV daily for 6 weeks.

Prosthetic Valve Endocarditis (PVE)

Key Point: Antibiotic durations are longer (≥6 weeks) due to increased relapse risk and local complications.

Outpatient Parenteral Antibiotic Therapy (OPAT)

Criteria for Switch: Clinical stability, infection control, completion of inpatient phase ≥10 days, no major complications.

Facilitates early discharge and improves quality of life while maintaining therapeutic efficacy. Continue same IV antibiotics or switch to oral step-down if susceptibility allows.

Surgical Indications & Timing

Surgery in IE aims to remove infected material and address hemodynamic consequences. Up to 20% of IE patients require surgery in the acute phase.

Three Main Indications

1. Heart Failure (40%)

  • Acute severe regurgitation causing pulmonary edema/cardiogenic shock
  • Septal perforation, prosthetic valve dehiscence
  • Timing: Emergency within 24h if cardiogenic shock; Urgent 3–5 days if controlled HF

2. Uncontrolled Infection (40%)

  • Persistent positive blood cultures >7 days despite antibiotics
  • Local complications: perivalvular abscess, pseudoaneurysm, fistulae
  • Resistant organisms: fungi, MRSA, Gram-negatives
  • Timing: Urgent 3–5 days; Non-urgent within same admission if controlled

3. Prevention of Systemic Embolism (20%)

  • Large mobile vegetations ≥10 mm
  • Documented systemic/pulmonary embolism
  • Anterior mitral valve vegetations (highest risk)
  • Timing: Urgent 3–5 days if recurrent emboli despite antibiotics
TimingTime FrameClinical Scenario
EmergencyWithin 24hCardiogenic shock, pulmonary edema refractory to medical therapy
Urgent3–5 daysUncontrolled infection, large vegetations, severe HF
Non-urgentSame admissionIE controlled, hemodynamics stable

Imaging: Echocardiography, CT, PET/CT, MRI

Transthoracic & Transesophageal Echocardiography

First-line diagnostic modality. TTE should be performed urgently in all suspected IE; TOE recommended if TTE inconclusive.

TTE Findings: Vegetations, paravalvular abscess, prosthetic valve dehiscence, severe acute regurgitation, conduction abnormalities.
TOE Advantages: Superior sensitivity (85–95% vs 60%), better visualization of posterior structures and prosthetic valves, 3D reconstruction for surgical planning.

Cardiac Computed Tomography (CT)

Recommended in: Suspected NVE, PVE, paravalvular complications, aortic root pathology, inconclusive echo. Highly sensitive for small vegetations and abscesses.

[18F]FDG-PET/CT & WBC SPECT/CT

Recommended for: IE and cardiac complications diagnosis, detection of distant septic emboli, CIED-related IE, inconclusive echocardiography. Sensitivity 65–90%, Specificity 85–90%.

Brain Imaging (MRI & CT)

Mandatory when neurological complications suspected (stroke, TIA, mycotic aneurysm). MRI more sensitive for small lesions; CT useful for acute hemorrhage.

Complications of Infective Endocarditis

Embolic Events (20–50%)

Large, mobile vegetations carry highest embolic risk. Risk highest during early antibiotic therapy due to inflammation and bacterial biofilm breakdown.

Heart Failure (40–60%)

Leading indication for urgent/emergency surgery. Caused by acute valvular regurgitation, septal perforation, or myocarditis.

Uncontrolled Infection

Persistent positive blood cultures >7 days despite appropriate antibiotics. Indicates insufficient antimicrobial efficacy or inaccessible infection source.

Neurological Complications (30–80%)

Most common: ischemic stroke from septic emboli. Also mycotic aneurysms, intracerebral hemorrhage, meningitis. S. aureus more frequently associated with neurological complications.

Pearl: Early cardiac surgery in high-risk neurological IE patients improves outcomes. Timing must balance hemorrhagic risk against embolic risk.

Perivalvular Abscess & Mycotic Aneurysms

Prosthetic Valve Endocarditis

PVE is the most severe form of IE with higher mortality and morbidity than NVE. Surgical management often necessary.

Epidemiology

Diagnosis of PVE

More challenging than NVE due to prosthetic material artifact. TOE essential; Cardiac CT helpful for perivalvular abscesses; [18F]FDG-PET/CT improves accuracy.

Management

Antibiotic Duration: ≥6 weeks minimum (longer than NVE).

Surgical Indications: Early valve replacement more frequently needed in PVE due to prosthetic valve dehiscence, paravalvular abscess, uncontrolled infection, systemic emboli.

Prognosis: In-hospital mortality 20–40% (higher than NVE). Early surgical intervention improves outcomes.

Cardiac Device-Related Infective Endocarditis

Definition

CIED-related IE involves the device, leads, or cardiac valves. Two categories: pocket infection (superficial) and lead-related/valvular IE (systemic).

Diagnosis

Presentation: Fever, device pocket infection signs, positive blood cultures, embolic phenomena.

Workup: Blood cultures, TTE & TOE, Cardiac CT, [18F]FDG-PET/CT or WBC SPECT/CT, Chest X-ray.

Management

Device Extraction

  • Complete system extraction recommended for all confirmed CIED-related IE
  • Perform at distant site once signs/symptoms resolve and blood cultures negative ≥72h
  • Percutaneous extraction preferred; surgical if percutaneous unsuccessful

Antibiotic & Device Replacement

  • Duration: 2–6 weeks post-extraction depending on organism and extent
  • MRSA coverage initially (vancomycin ± gentamicin/rifampicin)
  • Reimplantation timing: After infection signs resolved, blood cultures negative ≥72h

Right-Sided Infective Endocarditis

Accounts for 5–10% of IE; typically associated with IVDU. Often more amenable to medical management than left-sided IE.

Epidemiology & Clinical Features

Management

Medical Management (Preferred if Feasible)

  • Antibiotic therapy for S. aureus: flucloxacillin/cefazolin 4 weeks OR vancomycin 4–6 weeks if MRSA
  • Gentamicin first 2 weeks optional but recommended
  • Success rates 70–90% with appropriate antibiotics and close follow-up

Surgical Indications

  • Severe tricuspid regurgitation with HF refractory to diuretics
  • Large vegetations (>20 mm) with recurrent septic pulmonary emboli
  • Prosthetic valve IE with dysfunction
  • Uncontrolled infection with Gram-negative or fungal organisms

Surgical Options & Prognosis

Infective Endocarditis Prophylaxis

Antibiotic prophylaxis reduces bacteremia after dental and certain medical procedures. Indicated in high-risk patients undergoing procedures with significant bacteremia risk.

High-Risk Patients

Procedures Requiring Prophylaxis

ScenarioAntibioticDose & Timing
No penicillin allergyAmoxicillin2g orally 30–60 min before procedure
Allergy to penicillinCephalexin or Cephalosporin1g IV before procedure
Severe beta-lactam allergyClindamycin600 mg orally 30–60 min before
Unable to take oralAmpicillin IV2g IV 30–60 min before procedure

Key Points: Single pre-procedure dose adequate; no additional doses after procedure. Prophylaxis duration minimal.

Special Populations

Prosthetic Valve Endocarditis (PVE)

Extended antibiotic duration (≥6 weeks), higher surgical rate, worse prognosis than NVE. See Section: Prosthetic Valve Endocarditis.

Chronic Kidney Disease (CKD)

People Who Inject Drugs (PWID)

Elderly (>60–65 years)

Congenital Heart Disease (CHD)

Do's and Don'ts

DO:

  • Obtain ≥3 separate blood cultures BEFORE starting antibiotics
  • Consult Endocarditis Team early (within 24–48 hours)
  • Perform both TTE and TOE for cardiac assessment
  • Start empiric antibiotics immediately after blood cultures
  • Consider advanced imaging (CT, PET/CT) if diagnosis uncertain
  • Refer urgently to cardiac surgery if indications develop
  • Monitor antibiotic levels (vancomycin, gentamicin)
  • Plan endocarditis team follow-up during antibiotic therapy

DON'T:

  • Start antibiotics before blood cultures (reduces sensitivity)
  • Delay antibiotics excessively if IE clinically suspected
  • Rely on TTE alone if quality poor
  • Use short antibiotic courses (<4 weeks for NVE) without justification
  • Ignore persistently positive blood cultures
  • Delay neuroimaging if neurological symptoms develop
  • Use oral antibiotics alone for initial acute IE treatment
  • Minimize addictive disorder treatment in IVDU with IE

Useful Calculators for IE Management

These calculators help stratify risk, guide treatment decisions, and assess prognosis in endocarditis and related cardiovascular conditions.

Key References & Information

Official Guideline Citation

2023 ESC Guidelines for the management of infective endocarditis. Developed by the Task Force on Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by EACTS and EANM.

DOI: https://doi.org/10.1093/eurheartj/ehad193

Published: European Heart Journal (2023), 44(48):3948–4042

Recommendation Classes

Levels of Evidence

Disclaimer: This quick reference is a condensed educational summary of the 2023 ESC Guidelines. For complete details, recommendations, and evidence tables, consult the full guideline published in the European Heart Journal. Clinical decisions should always be individualized based on patient factors, local epidemiology, and expert consensus within the Endocarditis Team.