What antibiotics should be used to treat a patient with infective endocarditis, considering the causative organism and potential complications such as impaired renal function?

Antibiotic Selection for Infective Endocarditis

The choice of antibiotics for infective endocarditis depends primarily on the causative organism identified through blood cultures, the type of valve involved (native vs. prosthetic), and the patient's renal function. 1

Empirical Therapy (Before Organism Identification)

When treating acutely ill patients before pathogen identification, empirical coverage must target the most likely organisms:

Native Valve Endocarditis

• Vancomycin 30-60 mg/kg/day IV in 2-3 doses PLUS gentamicin 3 mg/kg/day IV/IM in 1 dose provides coverage for staphylococci, streptococci, and enterococci 1
• Draw three sets of blood cultures at 30-minute intervals before initiating antibiotics 1

Prosthetic Valve Endocarditis

• Vancomycin 30-60 mg/kg/day IV PLUS gentamicin 3 mg/kg/day IV PLUS rifampin 900-1200 mg/day for at least 6 weeks 1
• Start rifampin 3-5 days after vancomycin and gentamicin to reduce initial bacterial load 1

Organism-Specific Therapy

Streptococcal Endocarditis (Penicillin-Susceptible, MIC ≤0.12 μg/mL)

For native valve endocarditis, penicillin G 24 million units/day IV continuously or in 4-6 divided doses for 4 weeks achieves >98% cure rates 1, 2

Alternative regimens:

• Ceftriaxone 2 g/day IV once daily for 4 weeks (simplifies outpatient therapy) 1
• Penicillin G 24 million units/day IV PLUS gentamicin 3 mg/kg/day for 2 weeks (shorter duration option for uncomplicated cases) 1, 2

For prosthetic valve endocarditis:

• Extend therapy to 6 weeks with penicillin or ceftriaxone PLUS gentamicin for the first 2 weeks 1

Streptococcal Endocarditis (Relatively Resistant, MIC 0.12-0.5 μg/mL)

• Penicillin G 24 million units/day IV or ceftriaxone 2 g/day IV for 4 weeks PLUS gentamicin 3 mg/kg/day for the first 2 weeks 1

Enterococcal Endocarditis

For beta-lactam and gentamicin-susceptible strains, ampicillin 200 mg/kg/day IV in 4-6 doses PLUS gentamicin 3 mg/kg/day IV for 2-6 weeks is the standard regimen 1

For aminoglycoside-resistant enterococci:

• Ampicillin 2 g IV every 4 hours PLUS ceftriaxone 2 g IV every 12 hours for 6 weeks (double beta-lactam therapy) 1, 3
• This combination is active against E. faecalis with high-level aminoglycoside resistance and avoids nephrotoxicity 3
• This regimen is NOT active against E. faecium 1

For penicillin-allergic patients or penicillin-resistant strains:

• Vancomycin 30 mg/kg/day IV in 2 doses PLUS gentamicin 3 mg/kg/day for 6 weeks 1
• Vancomycin-gentamicin combinations carry higher nephrotoxicity and ototoxicity risks than penicillin-gentamicin 1

Duration considerations:

• Native valve with symptoms <3 months: 4 weeks minimum 1
• Native valve with symptoms >3 months or prosthetic valve: 6 weeks minimum 1, 2

Staphylococcal Endocarditis

Methicillin-Susceptible Staphylococcus aureus (MSSA)

For native valve endocarditis, (flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks PLUS gentamicin 3 mg/kg/day for the first week 1, 4

For prosthetic valve endocarditis:

• (Flu)cloxacillin or oxacillin 12 g/day IV PLUS rifampin 900-1200 mg/day PLUS gentamicin 3 mg/kg/day for 2 weeks, continue oxacillin and rifampin for ≥6 weeks total 1

Methicillin-Resistant Staphylococcus aureus (MRSA)

Vancomycin 30-60 mg/kg/day IV in 2-3 doses for 4-6 weeks (native valve) or ≥6 weeks (prosthetic valve) 1

• Target vancomycin trough levels ≥20 mg/L and AUC/MIC >400 1

Alternative for MRSA:

• Daptomycin 10 mg/kg/day IV once daily for 4-6 weeks 1, 5
• Daptomycin is superior to vancomycin for MSSA and MRSA bacteremia when vancomycin MIC >1 mg/L 1
• Monitor CPK levels weekly due to risk of myopathy 1, 5

For penicillin-allergic patients with non-anaphylactic reactions:

• Cefazolin 6 g/day or cefotaxime 6 g/day IV in 3 doses 1

HACEK Organisms

Ceftriaxone 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 1

• HACEK organisms include Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella species 1
• Ampicillin is no longer first-line due to beta-lactamase production 1

Blood Culture-Negative Endocarditis

For suspected Bartonella:

• Doxycycline 100 mg every 12 hours orally for 4 weeks PLUS gentamicin 3 mg/kg/day IV for 2 weeks 1

For suspected Coxiella burnetii (Q fever):

• Doxycycline 200 mg/24 hours PLUS hydroxychloroquine 200-600 mg/24 hours orally for ≥18 months 1

Critical Considerations for Renal Impairment

Gentamicin should be avoided or dose-adjusted in patients with creatinine clearance <50 mL/min 1

• Monitor serum gentamicin levels and renal function twice weekly in renal failure 1
• Single daily dosing of gentamicin reduces nephrotoxicity compared to divided doses 1

Vancomycin requires significant dose adjustment and therapeutic drug monitoring in renal impairment 1, 6

For patients with severe renal impairment and staphylococcal infection, consider:

• Trimethoprim-sulfamethoxazole 160-320 mg TMP/800-1600 mg SMX orally every 12 hours (minimal dose adjustment needed) 6
• Doxycycline 100 mg orally every 12 hours (no dose adjustment required) 6

Daptomycin dosing should be adjusted to 6 mg/kg every 48 hours in severe renal impairment (CrCl <30 mL/min) 6

Common Pitfalls to Avoid

• Do not use double beta-lactam therapy for E. faecium—it is only effective against E. faecalis 1, 3
• Avoid streptomycin in patients with creatinine clearance <50 mL/min 1
• Do not use daptomycin for pneumonia—it is inactivated by pulmonary surfactant 5
• Monitor for daptomycin resistance in persistent S. aureus bacteremia—increasing MIC indicates treatment failure 5
• Patients with baseline creatinine clearance <50 mL/min have significantly lower cure rates with standard dosing 5
• Rifampin should never be used as monotherapy due to rapid resistance development 1
• For prosthetic valve endocarditis with root abscess, extend therapy to 6 weeks IV followed by 3-6 months oral antibiotics based on inflammatory markers 7