From:  Fungal endocarditis: microbial insights, diagnostic and therapeutic challenges in the modern era

 Treatment approaches for FE

ApproachAgent/InterventionRegimen/IndicationsKey considerationsReferences
First-line antifungalsLiposomal amphotericin B (LAmB)3–5 mg/kg/day IV; ± flucytosine (25 mg/kg Q6h) for synergyNephrotoxic; monitor creatinine/electrolytes[48, 49]
Echinocandins (caspofungin, micafungin)Preferred for Candida; alternative to LAmB in renal impairmentLess effective against C. parapsilosis; biofilm penetration is limited[49, 79]
Azoles (voriconazole, posaconazole)Consolidation: voriconazole (Aspergillus); fluconazole (Candida, susceptible strains)TDM required; hepatotoxic/QT prolongation; drug interactions (CYP450)[51, 55]
Surgical interventionValve replacement/device removalIndications: heart failure, abscess, vegetations > 10 mm, persistent fungemia, embolic riskReduces mortality by 80% vs. medical therapy alone; perform early (within 1–2 weeks)[5, 23, 63, 64]
Pathogen-specificC. aurisRezafungin (once-weekly echinocandin); combination therapy (LAmB + echinocandin)Intrinsic multidrug resistance[69, 77]
AspergillusVoriconazole (primary); LAmB if contraindicatedGalactomannan/PCR guides diagnosis[15, 55]
Trichosporon/LomentosporaLAmB + voriconazole (echinocandin-resistant)Salvage therapy[57, 59]
Novel therapiesRezafunginLong-acting echinocandin; weekly IV dosingLimited FE data; active against resistant Candida[69, 70]
IbrexafungerpOral triterpenoid; biofilm penetration; broad activityPending IE trials[71]
NDV-3A vaccine (Als3p target)Preclinical; enhances host immunity against C. aurisNot yet human-tested[72]

FE: fungal endocarditis; IE: infective endocarditis; PCR: polymerase chain reaction; TDM: therapeutic drug monitoring; C. auris: Candida auris; C. parapsilosis: Candida parapsilosis