From the Guidelines
For refractory Candida parapsilosis endocarditis, a salvage regimen typically consists of combination antifungal therapy with an echinocandin (such as caspofungin 150 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg daily) plus high-dose liposomal amphotericin B (3-5 mg/kg/day), as recommended by the Infectious Diseases Society of America 1.
Key Considerations
- The choice of echinocandin and the dose of liposomal amphotericin B should be based on the patient's renal function and other comorbidities.
- Surgical intervention is crucial for removing infected valves and vegetations, and treatment duration should be at least 6 weeks after valve replacement, with blood cultures monitored weekly to confirm clearance of infection 1.
- Some cases may benefit from adding flucytosine (25 mg/kg 4 times daily) as a third agent, although this should be done with caution due to the potential for toxicity.
- Therapeutic drug monitoring is essential to ensure adequate drug levels while minimizing toxicity, particularly for amphotericin B.
Treatment Approach
- The aggressive combination approach is necessary because C. parapsilosis can form biofilms that reduce antifungal penetration and effectiveness.
- The echinocandins target the fungal cell wall while amphotericin B disrupts the cell membrane, providing synergistic activity against resistant organisms.
- Regular monitoring of renal function, electrolytes, and liver enzymes is critical due to the potential toxicity of these medications, particularly amphotericin B.
Additional Recommendations
- For patients who cannot undergo valve replacement, long-term suppression with fluconazole (400-800 mg daily) may be considered if the isolate is susceptible 1.
- Chronic suppressive antifungal therapy with fluconazole (400-800 mg daily) is recommended to prevent recurrence in patients with prosthetic valve endocarditis 1.
From the FDA Drug Label
In clinical trials, patients with candidemia received 3 mg/kg intravenous infusion every 12 hours as primary therapy, while patients with other deep tissue Candida infections received 4 mg/kg every 12 hours as salvage therapy.
The recommended salvage regimen for refractory Candida parapsilosis endocarditis is not directly addressed in the provided drug label. However, based on the information provided for other deep tissue Candida infections, a possible salvage regimen could be 4 mg/kg of voriconazole every 12 hours. It is essential to note that the provided label does not explicitly mention Candida parapsilosis or endocarditis, and the treatment should be guided by clinical judgment and expertise. 2
From the Research
Salvage Regimen for Refractory Candida parapsilosis Endocarditis
The treatment of refractory Candida parapsilosis endocarditis often requires a combination of antifungal therapies. Some studies suggest the following options:
- Combination antifungal therapy with micafungin and fluconazole, or micafungin, flucytosine, and fluconazole, without surgical intervention 3
- Long-term suppressive therapy with oral fluconazole for patients who are nonsurgical candidates or unable to tolerate long-term administration of amphotericin B with or without flucytosine 4
- Treatment with anidulafungin and fluconazole, which has been reported to cure a case of Candida parapsilosis bileaflet mitral valve endocarditis 5
- Use of liposomal amphotericin B and flucytosine, followed by surgical replacement of the infected valve and maintenance therapy with oral fluconazole 6
- Combination of caspofungin and voriconazole, which has been successfully used to treat a case of Candida parapsilosis mural endocarditis 7
Key Considerations
When selecting a salvage regimen, it is essential to consider the patient's overall health, the severity of the infection, and the potential risks and benefits of each treatment option. The use of combination antifungal therapy and long-term suppressive therapy may be necessary to effectively manage refractory Candida parapsilosis endocarditis.