Fungal endocarditis with heart valve replacement and atrial fibrillation posing a treatment challenge

Abstract

Rationale: Fungal endocarditis (FE) is a rare disease, in which antifungal treatment is necessary. When FE is complicated with prosthetic heart valve and/or atrial fibrillation, the coadministration of antifungal agents and warfarin is inevitable. We report a case of rheumatic heart disease with atrial fibrillation who developed FE following prosthetic heart valve replacement. The international normalized ratio (INR) increased significantly during the antifungal treatment with fluconazole. A discussion of the antifungal strategy in FE patients with prosthetic heart valves and/or atrial fibrillation and the interaction between antifungal agents and warfarin was performed. Patient concerns: A 54-year-old Chinese woman experienced intermittent fevers, aphemia, and weakness in her right extremities. Her temperature was 38.7°C, and there was atrial fibrillation with heart rate 110 times/min. Neurological examination revealed that she had drowsiness, Broca aphasia, right central facial paralysis, and hemiplegia (Medical Research Council scale, upper limb grade 0, lower limb grade II). Diagnoses: Multiple infarction on magnetic resonance imaging and the occlusion of left middle cerebral artery suggested the occurrence of cerebral embolism. The presence of Candida parapsilosis in the results of 4 blood cultures and the existence of valve vegetation in the reexamination of echocardiogram supported the diagnosis of FE. Interventions: The patient was given antifungal therapy with fluconazol. The INR increased dramatically on the 9th day of antifungal treatment, and subcutaneous bruising occurred at the intravenous infusion site. The antagonist of vitamin K1 was used and warfarin was reduced to a smaller dosage. The antifungal agent was replaced with caspofungin. Outcomes: Her speech improved significantly, and the muscle strength of her paralyzed side reached the Medical Research Council scale of grade IV + . She continued to receive caspofungin for antifungal treatment with relatively stable INR and waited for heart valve surgery. Lessons: The choice of antifungal agents is often a big challenge for FE patients, especially when they need warfarin for anticoagulation. It is better to administer a low dose of warfarin while carefully monitoring the INR or choose the antifungal drugs with little or no effect on warfarin.

“Not much room for mushrooms” in the heart: knowns and unknowns of fungal infective endocarditis

“…As a result, many complications may be underreported and there might be a publication bias concerning the uniqueness of a case or an unexpected outcome. This could be the reason for the surprisingly low mortality rate of the current case series, particularly those with prosthetic valve endocarditis (PVE) [1,53,58,80,89,103,107] . However, in line with prior observations, Candida species, with a reported 40%-60% rate [44,52,57,60,69,62,94,96,123,126] , is the most frequently reported infectious agent in the current case series.…”

“…Candida parapsilosis is the most frequent non-albicans fungus causing IE ] and exhibits an escalating trend [11,53] . Corresponding with prior reports, the outcomes associated with Candida-related IE in the current case series are more favorable and cardiac surgery protects against early death.…”

“…In 86 reports, 91 cases of definitive fungal IE were described. These reports involved fifteen cases with Candida parapsilosis [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] , seven cases with C. albicans [55][56][57][58][59][60][61] , three cases with C. tropicalis [62][63][64] , eight other species with Candida [65][66][67][68][69][70][71][72] , eight cases with Candida with a bacterium [73][74][75][76][77][78][79][80] , ten cases with Aspergillus fumigatus [81][82][83][84][85][86][87][88][89]…”

Antifungal Drugs TDM: Trends and Update

“…AF TDM cases in real-life settings (pathogens, underlying diseases, 69,71–73,75,81 trends per year, 84,234,235,236,238,239,241,244,245,344–348 CNS 532–539 localization 541–566 ) 364,370,499,522,527–530 Trends are concerning a majority of mucomycosis and aspergillosis, in oncohematology and transplantation. VRZ, more recently PSZ tablets and ISZ are the most represented.…”

A physiologically‐based pharmacokinetic/pharmacodynamic modeling approach for drug–drug‐gene interaction evaluation of S‐warfarin with fluconazole

“…Fluconazole is a commonly used antifungal drug in clinical practice, which is a moderate inhibitor of CYP2C9 and CYP3A4. 17 , 18 The concomitant use of fluconazole is required in some patients taking warfarin, 19 , 20 , 21 but the interaction between the two drugs makes it difficult to manage the dose. Several studies have described the effect of fluconazole on the anticoagulant effect of warfarin, 22 , 23 proposing pharmacokinetic (PK)‐based methods of dose adjustment.…”