What are the latest treatment guidelines for infective endocarditis?

Infective Endocarditis Treatment Guidelines

The 2015 European Society of Cardiology guidelines provide the most comprehensive framework for treating infective endocarditis, emphasizing immediate empirical therapy after blood cultures, pathogen-directed definitive treatment, and a multidisciplinary team approach involving infectious disease specialists and cardiac surgeons. 1, 2

Initial Diagnostic Steps

• Obtain three sets of blood cultures at 30-minute intervals before starting antibiotics 2
• Begin empirical antibiotic therapy immediately after blood cultures are drawn in acutely ill patients 2
• Consultation with an infectious disease specialist is mandatory for all cases 1, 2

Empirical Therapy (Before Pathogen Identification)

Community-Acquired Native Valve or Late Prosthetic Valve Endocarditis (≥12 months post-surgery)

• Ampicillin 12 g/day IV in 4-6 doses PLUS (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose (Class IIa, Level C) 1, 2
• For penicillin-allergic patients: Vancomycin 30-60 mg/kg/day IV in 2-3 doses PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose (Class IIb, Level C) 1

Early Prosthetic Valve Endocarditis (<12 months post-surgery) or Healthcare-Associated Endocarditis

• Vancomycin 30 mg/kg/day IV in 2 doses PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose PLUS Rifampin 900-1200 mg/day IV or oral in 2-3 divided doses 1, 2
• Critical caveat: Start rifampin 3-5 days after vancomycin and gentamicin to avoid antagonism against planktonic bacteria 1
• This regimen covers methicillin-resistant staphylococci, enterococci, and non-HACEK Gram-negative pathogens 1

Definitive Pathogen-Directed Therapy

Methicillin-Susceptible Staphylococcus aureus (MSSA)

Native Valve:

• (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks (Class I, Level B) 1, 2
• Do NOT add gentamicin—no clinical benefit demonstrated and increases renal toxicity 1, 2

Prosthetic Valve:

• (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for ≥6 weeks PLUS Rifampin 900-1200 mg IV or oral in 2-3 divided doses for ≥6 weeks PLUS Gentamicin 3 mg/kg/day IV or IM for 2 weeks (Class I, Level B) 1
• Gentamicin can be given once daily to reduce renal toxicity 1
• Staphylococcus aureus prosthetic valve endocarditis carries >45% mortality and often requires early valve replacement 1

Methicillin-Resistant Staphylococcus aureus (MRSA)

Native Valve:

• Vancomycin 30-60 mg/kg/day IV in 2-3 doses for 4-6 weeks (Class I, Level B) 1
• Maintain serum trough vancomycin levels ≥20 mg/L; target AUC/MIC >400 1
• Alternative: Daptomycin 10 mg/kg/day IV once daily for 4-6 weeks (Class IIa, Level C) 1, 2
• Daptomycin is superior to vancomycin for MSSA and MRSA bacteremia when vancomycin MIC >1 mg/L 1

Prosthetic Valve:

• Vancomycin 30 mg/kg/day IV in 2 doses for ≥6 weeks PLUS Rifampin 900-1200 mg for ≥6 weeks PLUS Gentamicin 3 mg/kg/day for 2 weeks 1

Enterococcal Endocarditis

Beta-lactam and Gentamicin-Susceptible Strains:

• Ampicillin (or amoxicillin) 200 mg/kg/day IV in 4-6 doses PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose for 4-6 weeks (Class I, Level B) 1, 2
• 6-week therapy recommended for prosthetic valve endocarditis or symptoms >3 months 1
• Ampicillin/amoxicillin preferred over penicillin G due to 2-4 times lower MICs 1

High-Level Aminoglycoside Resistance (HLAR, MIC >500 mg/L):

• Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS Ceftriaxone 4 g/day IV or IM in 2 doses for 6 weeks (Class I, Level B) 1
• This combination is active against Enterococcus faecalis with HLAR but NOT against E. faecium 1
• If streptomycin-susceptible, replace gentamicin with streptomycin 15 mg/kg/day in 2 divided doses 1

Vancomycin-Resistant Enterococci:

• Daptomycin 10 mg/kg/day PLUS Ampicillin 200 mg/kg/day IV in 4-6 doses 1
• Alternative: Linezolid 600 mg IV or oral twice daily for ≥8 weeks (Class IIa, Level C) with hematological toxicity monitoring 1

Streptococcal Endocarditis (Viridans Group, Streptococcus bovis)

Penicillin-Susceptible (MIC ≤0.125 mg/L):

• Penicillin G or ceftriaxone for 4 weeks 2, 3
• Short-course option: Penicillin G or ceftriaxone PLUS Gentamicin for 2 weeks for uncomplicated native valve cases 3

Blood Culture-Negative Infective Endocarditis

• Ampicillin-sulbactam 3 g IV every 6 hours PLUS Gentamicin 1 mg/kg IV or IM every 8 hours 2
• If no clinical response, extend antibiotic spectrum to cover atypical pathogens (doxycycline, quinolones) 1
• Consider surgery for molecular diagnosis and treatment 1
• Mandatory infectious disease specialist consultation 1, 2

Duration of Therapy

• Native valve endocarditis: 4-6 weeks for most pathogens 1, 2
• Prosthetic valve endocarditis: Minimum 6 weeks for all cases 1, 2
• Extend duration if complications develop or slow clinical response 2

Critical Monitoring Requirements

• Therapeutic drug monitoring: Vancomycin trough levels ≥20 mg/L; gentamicin levels monitored weekly (twice weekly in renal failure) 1
• Monitor creatine phosphokinase (CPK) weekly when using daptomycin 1
• Limit aminoglycoside use to maximum 2 weeks to reduce nephrotoxicity 2
• Follow-up blood cultures to document clearance of bacteremia 2

Outpatient Parenteral Antibiotic Therapy (OPAT)

Critical Phase (Weeks 0-2):

• Inpatient treatment strongly preferred 1
• Consider OPAT only for oral streptococci or S. bovis native valve endocarditis in stable patients without complications 1

Continuation Phase (Beyond Week 2):

• Consider OPAT if medically stable without heart failure, concerning echocardiographic features, neurological signs, or renal impairment 1
• Requires daily nurse evaluation and physician assessment 1-2 times weekly 1

Surgical Indications

• Approximately 50% of patients require surgical intervention 1
• Early surgery indicated for: severe heart failure, uncontrolled infection, perivalvular abscess, prosthetic valve dehiscence, large mobile vegetations with embolic risk 2
• Staphylococcus aureus prosthetic valve endocarditis often requires early valve replacement due to >45% mortality 1

Common Pitfalls to Avoid

• Never add gentamicin to MSSA native valve endocarditis—no benefit, only toxicity 1, 2
• Do not use aminoglycosides in enterococcal endocarditis with high-level resistance (MIC >500 mg/L)—synergy is lost 1
• Avoid starting rifampin simultaneously with other antibiotics in staphylococcal prosthetic valve endocarditis—wait 3-5 days to prevent antagonism 1
• Rifampin increases hepatic metabolism of warfarin and other drugs—adjust doses accordingly 1