What is the recommended treatment for fungal endocarditis in an adult, including the antifungal regimen and surgical valve removal?

Treatment of Fungal Endocarditis

Fungal endocarditis requires aggressive combined therapy consisting of surgical valve replacement plus prolonged antifungal therapy with amphotericin B-based regimens (or echinocandins for Candida), followed by lifelong oral azole suppression. 1

Initial Induction Phase (Control of Infection)

Surgical Intervention

• Valve surgery should be performed in most cases of fungal endocarditis and is considered a "stand-alone indication" for surgical replacement of the infected valve. 1
• For Candida endocarditis specifically, meta-analysis of 879 cases demonstrated marked reduction in mortality (prevalence odds ratio 0.56) among patients who underwent adjunctive valve surgery. 1
• Surgery is particularly crucial for prosthetic valve fungal endocarditis, where it is considered mandatory regardless of the fungal species. 1
• Timing is critical: early surgical intervention maximizes outcomes, though survivor bias must be considered when interpreting surgical benefit data. 1

Antifungal Regimen

For Candida endocarditis:

• Combination therapy with amphotericin B plus flucytosine reduces mortality compared to antifungal monotherapy. 1
• Alternative approach: High-dose echinocandins (caspofungin 70 mg loading, then 50 mg daily; micafungin 100 mg daily; or anidulafungin 200 mg loading, then 100 mg daily) are increasingly used given their fungicidal activity. 2, 3
• Duration: Parenteral antifungal therapy for >6 weeks during the induction phase. 1

For Aspergillus endocarditis:

• Voriconazole is the preferred agent for Aspergillus species. 3
• Mortality remains extremely high (survival rate <20% for mold-related endocarditis). 1
• Blood cultures are rarely positive with Aspergillus, making this a cause of culture-negative endocarditis. 1

Long-Term Suppressive Phase

Lifelong Oral Azole Therapy

• After completing initial 6-week induction therapy, lifelong suppressive therapy with an oral azole (typically fluconazole) is reasonable and recommended. 1
• This applies to two populations:
  • Patients who completed combined medical-surgical induction therapy (to prevent relapse, which can occur years later). 1
  • Patients who responded to induction medical therapy but are not surgical candidates. 1
• Meta-analysis of 64 Candida endocarditis patients who were not surgical candidates showed 95% (20 of 21) survived with long-term fluconazole suppression during ≥6 months follow-up. 1

Special Considerations and Pitfalls

Diagnostic Challenges

• Blood cultures are positive in most Candida cases but rarely positive in Aspergillus endocarditis. 1
• Consider adjunctive diagnostics: β-D-glucan, galactomannan testing, and 18F-FDG PET/CT imaging. 4, 3
• Aspergillus represents culture-negative endocarditis, typically occurring in prosthetic valve patients. 1

Metastatic Complications

• Noncardiac sites of metastatic infection frequently complicate fungal endocarditis. 1
• Candida endocarditis can cause endophthalmitis requiring both systemic and intraocular antifungal therapy. 1
• Perform dilated eye examination within the first week of therapy in non-neutropenic patients. 2

High-Risk Populations

• Prosthetic valve recipients have particularly high risk, with 43% of cases occurring >1 year after valve placement. 1
• Cardiovascular devices (central venous catheters, pacemakers, defibrillators) are now more prevalent risk factors than traditional risks like injection drug use. 1

Critical Pitfalls to Avoid

• Do not attempt medical therapy alone without surgery in most cases—this dramatically reduces survival. 1
• Do not discontinue suppressive azole therapy after initial treatment completion—relapse rates are high and can occur years later. 1
• For Candida parapsilosis specifically, biofilm production on prosthetic valves makes treatment particularly challenging and requires aggressive combined approach. 5, 6
• Mortality remains unacceptably high (>70% overall) despite aggressive therapy, emphasizing the need for early recognition and intervention. 4, 3

Evolving Considerations

• While amphotericin B has historically been the initial drug of choice, newer fungicidal agents like echinocandins warrant consideration for Candida endocarditis given comparable efficacy and potentially better tolerability. 1
• The traditional doctrine that fungal endocarditis is an absolute surgical indication is being re-evaluated, though surgery remains recommended in most cases. 1