What are the 2025 ESC (European Society of Cardiology) guidelines for treating infective endocarditis?

ESC Guidelines for Infective Endocarditis (2023 Update)

The most recent ESC guidelines for infective endocarditis were published in 2023, representing a significant update from the 2015 version, with major paradigm shifts in antibiotic prophylaxis, diagnostic criteria, oral antibiotic therapy, surgical timing, and the central role of the multidisciplinary Endocarditis Team 1, 2, 3, 4, 5.

Key Updates and Management Principles

1. The Endocarditis Team Approach

All patients with suspected or confirmed IE must be managed by a specialized multidisciplinary Endocarditis Team 1, 3, 4. This team-based approach has been shown to improve diagnosis, optimize treatment decisions, and enhance survival outcomes. The team should include cardiologists, cardiac surgeons, infectious disease specialists, microbiologists, and imaging specialists 3, 4.

2. Antibiotic Prophylaxis - Refined Recommendations

The 2023 guidelines provide more detailed specifications for high-risk patients requiring antibiotic prophylaxis before dental procedures 1, 4, 5, 6:

High-risk patients requiring prophylaxis:

• Prosthetic heart valves or valve repair with prosthetic material
• Previous infective endocarditis
• Congenital heart disease (cyanotic lesions, repaired defects with residual shunts, or repairs with prosthetic material within 6 months)

Major change in antibiotic selection:

• Clindamycin has been removed from recommendations
• New alternatives include azithromycin and clarithromycin for penicillin-allergic patients 6

3. Diagnostic Criteria - Enhanced Imaging

Multimodality imaging has been significantly emphasized, with PET-CT now incorporated into diagnostic criteria for prosthetic valve endocarditis 3, 4, 5. TOE remains mandatory for adequate assessment before transitioning to outpatient therapy 1.

Critical diagnostic principle: Three sets of blood cultures must be drawn at 30-minute intervals before initiating antibiotics 7.

4. Antibiotic Therapy - Paradigm Shift to Oral Treatment

The 2023 guidelines introduce a major paradigm shift allowing partial oral antibiotic therapy (OAT) in select, clinically stable patients 2, 3, 4, 8.

Criteria for Oral Step-Down Therapy:

Eligible patients:

• Native valve endocarditis caused by viridans streptococci, Enterococcus faecalis, methicillin-susceptible S. aureus, or coagulase-negative staphylococci
• Clinically stable after ≥7 days of adequate IV antibiotic therapy
• No complications (heart failure, abscess, persistent bacteremia, embolic events)
• Ability to take and absorb oral medications
• Close outpatient monitoring capability 2, 3, 8

Oral regimens based on POET trial:

• High bioavailability antibiotics: amoxicillin, fluoroquinolones, linezolid, rifampicin
• Specific combinations depend on causative organism 8

Important caveat: This represents a significant departure from traditional 4-6 weeks of IV therapy, but is supported by the landmark POET randomized controlled trial demonstrating noninferiority 8.

5. Pathogen-Specific Treatment Regimens

Streptococcal IE (Penicillin-Susceptible):

• Penicillin G or ceftriaxone for 4 weeks (NVE) or 6 weeks (PVE)
• Short-course 2-week therapy: penicillin/ceftriaxone + gentamicin for uncomplicated NVE
• Ceftriaxone once daily is convenient for outpatient therapy 9

Staphylococcal IE:

Native valves (methicillin-susceptible):

• (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks
• Gentamicin addition for 3-5 days is optional (clinical benefit not formally demonstrated, increases toxicity) 9, 7, 9

Prosthetic valves (methicillin-susceptible):

• (Flu)cloxacillin 12 g/day IV for ≥6 weeks
• Plus rifampin 900-1200 mg/day for ≥6 weeks (started 3-5 days after initial therapy)
• Plus gentamicin 3 mg/kg/day for 2 weeks 9, 7, 9

Methicillin-resistant staphylococci:

• Vancomycin 30-60 mg/kg/day IV in 2-3 doses for 4-6 weeks (NVE) or ≥6 weeks (PVE)
• Target trough levels: 10-15 mg/L (NVE) or 25-30 mg/L (PVE)
• Alternative: Daptomycin 10 mg/kg/day IV (superior for MRSA with vancomycin MIC >1 mg/L) 9, 7, 9

Critical point: S. aureus PVE carries >45% mortality and often requires early valve replacement 9.

Enterococcal IE:

• Ampicillin (or amoxicillin) 12 g/day IV + gentamicin 3 mg/kg/day for 4-6 weeks
• If high-level aminoglycoside resistance (MIC >500 mg/L), do not use gentamicin - consider streptomycin or prolonged dual beta-lactam therapy 7

HACEK Organisms:

• Ceftriaxone 2 g/day IV for 4 weeks (NVE) or 6 weeks (PVE) - first-line due to beta-lactamase production
• Alternative: ciprofloxacin 400 mg IV q8-12h or 750 mg PO q12h 7

Non-HACEK Gram-Negative Bacteria:

• Early surgery plus ≥6 weeks of bactericidal beta-lactam + aminoglycoside combinations
• Mortality >50%
• Mandatory consultation with Endocarditis Team/ID specialist 7

Blood Culture-Negative IE:

Specific pathogens and regimens 7:

• Bartonella: Doxycycline 100 mg PO q12h × 4 weeks + gentamicin 3 mg/kg IV × 2 weeks
• Coxiella burnetii (Q fever): Doxycycline 200 mg/day + hydroxychloroquine 200-600 mg/day PO for >18 months (monitor hydroxychloroquine levels)
• Brucella: Doxycycline 200 mg/day + cotrimoxazole 960 mg q12h + rifampin 300-600 mg/day PO for ≥3-6 months
• Tropheryma whipplei: Doxycycline 200 mg/day + hydroxychloroquine 200-600 mg/day PO for ≥18 months

Fungal IE:

• Mortality >50%
• Requires combined antifungal therapy PLUS surgical valve replacement
• Most common in PVE, IV drug users, and immunocompromised patients 7

6. Empirical Therapy

Treatment must be started promptly after drawing three blood culture sets 7.

Community-acquired NVE or late PVE (≥12 months):

• Ampicillin 12 g/day IV + (flu)cloxacillin/oxacillin 12 g/day IV + gentamicin 3 mg/kg/day
• For penicillin allergy: Vancomycin 30-60 mg/kg/day IV + gentamicin 7

Early PVE (<12 months) or healthcare-associated IE:

• Vancomycin 30 mg/kg/day IV + gentamicin 3 mg/kg/day + rifampin 900-1200 mg/day
• Rifampin started 3-5 days after vancomycin/gentamicin 7

7. Surgical Indications and Timing

Surgery is required in approximately 50% of IE patients and is one of the most important protective factors against mortality 7, 1, 3. Failure to operate when indicated markedly worsens survival 1, 3.

Surgical Timing Definitions:

• Emergency: Within 24 hours
• Urgent: Within 3-5 days
• Non-urgent/Elective: Within same hospitalization but >5 days 7, 1, 3

Class I Indications (Must Operate):

Heart Failure:

• Emergency surgery: Severe acute regurgitation/obstruction/fistula causing refractory pulmonary edema or cardiogenic shock 7
• Urgent surgery: Severe regurgitation/obstruction with HF symptoms or poor hemodynamic tolerance on echo 7

Uncontrolled Infection:

• Urgent surgery: Locally uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) 7
• Urgent/elective surgery: Fungal IE or multiresistant organisms 7

Prevention of Embolism:

• Urgent surgery: Persistent vegetations >10 mm after ≥1 embolic episode despite appropriate antibiotics 7

Stroke and Surgical Timing - Critical Update:

Major 2023 guideline change:

• Embolic (ischemic) stroke should NOT delay surgery once indication identified 3
• Hemorrhagic stroke: Surgery may be delayed up to 4 weeks based on clinical condition 3

This represents a significant shift from previous conservative approaches to post-stroke surgery.

Prosthetic Valve Endocarditis:

• Early PVE (<6 months post-surgery) requires urgent surgical intervention 3
• PVE caused by S. aureus or non-HACEK Gram-negative bacteria is a surgical indication 7, 3

Important controversy: The Dutch guidelines recommend disregarding the new ESC Class I recommendation for surgery in all early PVE, suggesting more individualized assessment 2.

CIED-Associated IE:

• Complete device extraction is the gold standard - significantly improves survival
• Conservative treatment associated with increased mortality 1, 3

8. Outpatient Parenteral Antibiotic Therapy (OPAT)

OPAT is feasible for consolidation therapy once critical complications are controlled 7.

Critical phase (weeks 0-2):

• Preferred inpatient treatment
• Consider OPAT only for: oral streptococci/S. bovis, native valve, stable patient, no complications 7

Continuation phase (beyond week 2):

• Consider OPAT if medically stable
• Do NOT use OPAT if: HF, concerning echo features, neurological signs, renal impairment 7

Essential requirements:

• Patient/staff education
• Regular post-discharge evaluation (nurses daily, physician 1-2×/week)
• Physician-directed program 7

9. Prevention of Recurrence

Patients with previous IE require long-term surveillance and education 1:

• Good oral health maintenance mandatory
• Skin hygiene advice
• Immediate medical evaluation for fever/chills
• Timely, curative antibiotic therapy for all bacterial infections
• Antibiotic prophylaxis for high-risk procedures 1

Common Pitfalls to Avoid

1. Delaying surgery in patients with surgical indications - this is associated with markedly worse outcomes 1, 3

2. Adding gentamicin to staphylococcal NVE beyond 3-5 days - clinical benefit not demonstrated, increases nephrotoxicity 9, 7

3. Using aminoglycosides in enterococcal IE with high-level resistance (MIC >500 mg/L) - synergy is lost 7

4. Starting rifampin too early in staphylococcal PVE - wait 3-5 days to clear bacteremia first due to antagonistic effects 7, 9

5. Attempting conservative management of CIED-associated IE - complete extraction is mandatory 1, 3

6. Unnecessarily delaying surgery after ischemic stroke - new guidelines support proceeding with surgery 3

7. Transitioning to oral therapy in unstable patients or those with complications - strict criteria must be met 2, 3, 8

Important Notes on Evidence Quality

The 2015 ESC guidelines 7 remain the most detailed published ESC guidelines with specific antibiotic regimens and dosing tables. The 2023 guidelines represent an update with new concepts (oral therapy, refined prophylaxis, enhanced imaging, surgical timing) but the foundational antibiotic regimens from 2015 largely remain valid 2, 3, 4, 5.

Most evidence comes from observational studies and expert opinion rather than randomized trials 4. The POET trial for oral therapy is a notable exception providing Level B evidence 8.

The 2009 ESC guidelines 9 are outdated and superseded by 2015 and 2023 versions, though core antibiotic principles remain consistent across iterations.