What is the recommended dosing and monitoring for rifampin (Rifampin) in combination with vancomycin (Vancomycin) for treating complex infections such as prosthetic valve endocarditis or osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA)?

From the Guidelines

For complex MRSA infections like prosthetic valve endocarditis or osteomyelitis, rifampin should be used in combination with vancomycin, with rifampin dosed at 900-1200 mg i.v. or orally in 2 or 3 divided doses, alongside vancomycin 30-60 mg/kg/day i.v. in 2-3 doses, as recommended by the 2015 ESC guidelines for the management of infective endocarditis 1. The combination of rifampin and vancomycin is recommended for the treatment of prosthetic valve endocarditis caused by MRSA, with a duration of treatment of at least 6 weeks 1. Key considerations for this combination therapy include:

• Starting rifampin 3-5 days after initiating vancomycin therapy to ensure the primary infection is under control 1
• Monitoring vancomycin trough levels to maintain levels between 15-20 μg/mL 1
• Regular monitoring of liver function tests, complete blood counts, and vancomycin levels to minimize toxicity and ensure efficacy 1
• Being aware of potential drug interactions with rifampin, which induces cytochrome P450 enzymes and can reduce the effectiveness of various medications, including anticoagulants and oral contraceptives 1 The use of rifampin in combination with vancomycin is supported by its ability to eradicate bacteria attached to foreign material, such as prosthetic devices, and its synergistic effect with vancomycin in enhancing bacterial killing and penetration into biofilms 1.

From the Research

Recommended Dosing and Monitoring for Rifampin in Combination with Vancomycin

• The recommended dosing for rifampin in combination with vancomycin for treating complex infections such as prosthetic valve endocarditis or osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) is not well established, but studies suggest the following:
  • Rifampin 600 mg, i.v., o.d for 5 days 2
  • Rifampin 900-1,200 mg daily in combination with vancomycin for an average of 38 days 3
• Monitoring for rifampin and vancomycin combination therapy should include:
  • Serum vancomycin levels to ensure therapeutic range 2
  • Blood cultures to assess response to treatment 2, 3
  • Liver function tests to monitor for hepatotoxicity 4, 5
  • Renal function tests to monitor for nephrotoxicity 4, 5

Efficacy of Rifampin and Vancomycin Combination Therapy

• Studies have shown mixed results for the efficacy of rifampin and vancomycin combination therapy in treating MRSA infections:
  • A prospective study found that adding rifampin to vancomycin therapy resulted in a dramatic clinical response and survival of grafts in burn patients with MRSA septicaemia 2
  • A retrospective analysis found that switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin in patients with persistent MRSA bacteremia 4
  • A randomized open-label trial found that addition of rifampin to vancomycin did not affect cure rates in patients with MRSA endocarditis, but increased duration of bacteremia 4
  • A study found that rifampin treatment was associated with longer hospitalizations and hepatoxicity, nephrotoxicity, and drug-drug interactions leading to treatment discontinuation in 31% of patients 5

Limitations and Future Directions

• The existing clinical data do not suggest a benefit of either adjunctive gentamicin or rifampin in staphylococcal PVE, and recommendations for gentamicin and rifampin in PVE should be downgraded and primarily be used within the context of clinical trials 5
• Further studies, including randomized controlled trials, are needed to assess the efficacy and safety of rifampin and vancomycin combination therapy in treating complex MRSA infections 4, 6, 5