Rifampin and Aminoglycosides in Prosthetic Valve Staphylococcal Endocarditis
Yes, rifampin and aminoglycosides should still be used for prosthetic valve staphylococcal endocarditis, with aminoglycosides limited to the first 2 weeks of therapy. This recommendation is supported by current guidelines from the American Heart Association and European Society of Cardiology 1.
Treatment Regimen for Staphylococcal Prosthetic Valve Endocarditis
For Methicillin-Susceptible Staphylococci:
- Primary antibiotic: Nafcillin or oxacillin (12g/24h IV in 6 equally divided doses) for ≥6 weeks 1
- Plus rifampin: 900 mg/24h IV or orally in 3 equally divided doses for ≥6 weeks 1
- Plus gentamicin: 3 mg/kg/24h IV or IM in 2-3 equally divided doses for the first 2 weeks only 1
For Methicillin-Resistant Staphylococci:
- Primary antibiotic: Vancomycin (30 mg/kg/24h IV in 2 equally divided doses) for ≥6 weeks 1
- Plus rifampin: 900 mg/24h IV or orally in 3 equally divided doses for ≥6 weeks 1
- Plus gentamicin: 3 mg/kg/24h IV or IM in 2-3 equally divided doses for the first 2 weeks only 1
Rationale and Evidence
The combination therapy recommendation is based on:
Rifampin's unique role: In animal studies, rifampin has demonstrated a crucial role in the complete sterilization of foreign bodies infected by Staphylococcus aureus 1. It helps eradicate bacteria attached to foreign material, making it particularly valuable for prosthetic valve infections 1.
Aminoglycoside duration: The 2-week regimen of aminoglycoside is recommended due to the high morbidity and mortality rates associated with staphylococcal prosthetic valve endocarditis 1. However, this recommendation is based on limited clinical data.
Clinical experience: Evidence from models of experimental endocarditis and limited clinical experience suggests that the optimal antibiotic therapy for prosthetic valve endocarditis caused by coagulase-negative staphylococci is vancomycin combined with rifampin and gentamicin 1.
Important Considerations and Modifications
Gentamicin resistance: If the organism is resistant to gentamicin, an alternative aminoglycoside to which it is susceptible should be substituted 1.
Resistance to all aminoglycosides: If the organism is resistant to all available aminoglycosides, aminoglycoside treatment should be omitted. In this situation, if the organism is susceptible to a fluoroquinolone, it may be used instead of gentamicin 1.
Monitoring for rifampin resistance: Coagulase-negative staphylococci may become resistant to rifampin during therapy. Because of potential changes in antibiotic susceptibility patterns, organisms recovered from surgical specimens or blood from patients who have relapsed should be retested for antibiotic susceptibility 1.
Surgical intervention: Prosthetic valve infections, particularly when onset is within 12 months of cardiac valve implantation or when an aortic valve prosthesis is involved, are frequently complicated by perivalvular and myocardial abscesses and valvular dysfunction. Surgery is often required and may be lifesaving 1.
Recent Challenges to Current Guidelines
A 2022 systematic review and meta-analysis has questioned the benefit of adjunctive gentamicin and rifampin in staphylococcal prosthetic valve endocarditis 2. This review found that:
- Adding gentamicin to rifampin-containing regimens did not reduce clinical failure
- Adding rifampin to gentamicin-containing regimens did not reduce clinical failure
- Rifampin was associated with hepatotoxicity, nephrotoxicity, and drug-drug interactions
However, current guidelines from major cardiology and infectious disease societies still recommend the combination therapy approach described above 1.
Conclusion
Despite emerging questions about this approach, the current standard of care based on established guidelines still supports the use of rifampin for the full course of therapy (≥6 weeks) and gentamicin for the first 2 weeks when treating staphylococcal prosthetic valve endocarditis. This approach aims to maximize outcomes in a condition with significant mortality risk.