What is the recommended treatment for strep (streptococcal) endocarditis?

Treatment of Streptococcal Endocarditis

For penicillin-susceptible streptococcal endocarditis (MIC ≤0.12 μg/mL), treat with intravenous penicillin G or ceftriaxone for 4 weeks, which achieves cure rates exceeding 95%. 1

Native Valve Endocarditis: Penicillin-Susceptible Strains

Standard 4-Week Regimen (First-Line)

• Penicillin G 24 million units/24h IV continuously or in 4-6 divided doses for 4 weeks 1
• Alternative: Ceftriaxone 2 g IV/IM once daily for 4 weeks 1, 2
• Alternative: Ampicillin 12 g/24h IV in 4-6 divided doses for 4 weeks 1
• These monotherapy regimens are preferred for patients >65 years or with renal impairment to avoid aminoglycoside toxicity 1

Shortened 2-Week Regimen (For Uncomplicated Cases)

• Penicillin G 24 million units/24h IV (or ceftriaxone 2 g once daily) PLUS gentamicin 3 mg/kg/24h IV/IM once daily for 2 weeks 1
• This regimen achieves 98% cure rates in adults but is NOT recommended for children due to lack of pediatric data 1
• Contraindications to 2-week regimen: symptoms >3 months, extracardiac infection focus, intracardiac abscess, mycotic aneurysm, renal impairment, or concurrent nephrotoxic drugs 1
• Ceftriaxone plus gentamicin once-daily is particularly convenient for outpatient parenteral therapy 1, 2

Penicillin-Allergic Patients

• Vancomycin 30 mg/kg/24h IV in 2 divided doses for 4 weeks (target trough 10-15 μg/mL) 1
• Vancomycin should be infused over 1 hour to prevent "red man syndrome" 1
• When using vancomycin, gentamicin addition is not necessary 1

Native Valve Endocarditis: Relatively Resistant Strains (MIC 0.12-0.5 μg/mL)

Combination therapy is mandatory for relatively resistant strains to ensure bactericidal activity. 1

• Penicillin G 24 million units/24h IV (or ceftriaxone 2 g once daily or ampicillin 12 g/24h) for 4 weeks 1
• PLUS gentamicin 3 mg/kg/24h IV/IM once daily for the first 2 weeks only 1, 2
• This 4-week regimen with 2 weeks of gentamicin is the standard approach for moderately resistant organisms 1

Highly Resistant Strains (MIC >0.5 μg/mL) and Nutritionally Variant Streptococci

Treat these organisms with the same regimen used for enterococcal endocarditis due to higher failure rates. 1

• This includes Abiotrophia defectiva, Granulicatella species, and Gemella species 1, 3
• Ampicillin or penicillin G PLUS gentamicin for 4-6 weeks with infectious disease consultation 1
• These organisms have cure rates as low as 60% compared to 95%+ for susceptible strains, necessitating prolonged combination therapy 1, 3

Prosthetic Valve Endocarditis

Extend all treatment durations to 6 weeks for prosthetic valve or other prosthetic material infections. 1

Penicillin-Susceptible Strains (MIC ≤0.12 μg/mL)

• Penicillin G or ceftriaxone for 6 weeks with or without gentamicin for first 2 weeks 1, 3
• The addition of gentamicin has not demonstrated superior cure rates in highly susceptible strains but may be considered 1

Relatively/Highly Resistant Strains (MIC >0.12 μg/mL)

• Penicillin G or ceftriaxone for 6 weeks PLUS gentamicin for the entire 6 weeks 1
• For strains with MIC >0.5 μg/mL, use enterococcal regimen for full 6 weeks 1

Special Streptococcal Species

Streptococcus pneumoniae

• Penicillin G, cefazolin, or ceftriaxone for 4 weeks (6 weeks for prosthetic valves) 1
• For penicillin-resistant strains (MIC 0.1-4 μg/mL) without meningitis: high-dose penicillin or third-generation cephalosporin 1
• If meningitis present with resistant strain: high-dose cefotaxime or ceftriaxone; if MIC ≥2 μg/mL to cefotaxime, add vancomycin plus rifampin 1
• Infectious disease consultation is mandatory for pneumococcal endocarditis 1

Streptococcus pyogenes (Group A)

• Penicillin G IV for 4-6 weeks 1
• Ceftriaxone is a reasonable alternative 1

Groups B, C, F, and G β-Hemolytic Streptococci

• Penicillin or ceftriaxone for 4-6 weeks PLUS gentamicin for at least the first 2 weeks 1
• These organisms are slightly more resistant to penicillin than Group A streptococci, justifying combination therapy 1
• Early surgical intervention may improve survival in these aggressive infections 1

Monitoring and Safety

Aminoglycoside Monitoring

• Monitor gentamicin levels and renal function weekly 1, 3
• For once-daily dosing: trough <1 μg/mL, peak 10-12 μg/mL (1 hour post-infusion) 1
• For divided dosing: similar targets apply 1
• Vestibular toxicity occurs in approximately 3% of patients receiving streptomycin 4

Vancomycin Monitoring

• Target trough levels 10-15 μg/mL, peak 30-45 μg/mL 1, 3
• Monitor weekly along with renal function 1

Critical Pitfalls to Avoid

Do Not Use 2-Week Regimen If:

• Symptoms present >3 months 1
• Prosthetic valve or material present 1
• Intracardiac abscess or mycotic aneurysm 1
• Extracardiac infection focus 1
• Renal impairment or concurrent nephrotoxic drugs 1
• Pediatric patient (insufficient data) 1

Resistance Considerations

• Over 30% of viridans streptococci now show intermediate or full penicillin resistance, making susceptibility testing essential 1, 3
• Streptococcus mitis has particularly high resistance rates 3
• Some S. bovis strains are tolerant to penicillin (not killed despite low MIC), requiring combination therapy 5

Dosing Errors

• Gentamicin doses >3 mg/kg/day are associated with 100% nephrotoxicity rates versus 20% at ≤3 mg/kg/day 4
• Despite guidelines recommending divided gentamicin dosing for staphylococci/enterococci, once-daily dosing (3 mg/kg) is increasingly used based on literature evidence 6

Home Therapy Considerations

Outpatient parenteral antibiotic therapy is reasonable for carefully selected patients after initial stabilization. 1

• Requires stable clinical status, reliable family support, and access to home healthcare 1
• Ceftriaxone once-daily is ideal for outpatient therapy 1, 2
• Not appropriate for complicated cases requiring close monitoring 1