Discussion
Aortic valve fungal infections, although rare, represent a critical and life-threatening complication in patients with predisposing risk factors such as intravenous drug use, prosthetic heart valve implantation, and immunosuppression [7,8]. Candida species have emerged as significant etiological agents of these infections, with Candida parapsilosis being increasingly reported in recent years [9,10]. For instance, a multicenter study conducted by Lefort et al. found that C. parapsilosis accounted for 16% of all Candida species isolated from patients with fungal endocarditis [11]. Furthermore, a review by Pasha et al. reported a rise in the incidence of C. parapsilosisendocarditis, particularly in settings with high rates of prosthetic valve implantation [12]
C. parapsilosis is an opportunistic organism which is a normal commensal of the human gastrointestinal tract and the human skin, commonly found underneath the nails of the hands [13, 14]. Unlike other fungal causes of invasive disease such as C. tropicalis and C. albicans , invasive infections with C. parapsilosis can occur in the absence of prior colonization with the organisms. Notable risk factors in these cases are patients with preceding surgeries, usually of the gastrointestinal tract, immunocompromised patients such as those with Human Immunodeficiency Virus/Acquired-Immunodeficiency Disease Syndrome, critically-ill patients requiring long-term placement of invasive vascular lines; and neonates with very low birth weights [13]. Intravenous drug use is a known risk factor for invasive fungal infections with Candida species, particularly infections caused by C. parapsilosis [13].
C. parapsilosis has been recognized as an important pathogen in various invasive fungal infections, such as candidemia, meningitis, peritonitis, ocular infections, and endocarditis [9]. In cases ofC. parapsilosis endocarditis, the aortic valve is most commonly affected, with a demonstrated predilection for prosthetic aortic valves [15,16]. In the rare cases of C. parapsilosis endocarditis of a native valve, a history of intravenous drug use is usually present [17]. In both scenarios, endocarditis secondary to C. parapsilosis is usually preceded by fungemia [16, 17].
Distinguishing between candida and bacterial endocarditis during the initial assessment can pose significant challenges, as both can present with non-specific symptoms [18, 19]. Candida endocarditis typically presents as subacute endocarditis, and C. parapsilopasendocarditis is frequently associated with septic emboli, which may involve many organs due to its predilection for the aortic valve [19].
Definitive therapy for both native valve and prosthetic valve Candida endocarditis involves medical management, generally with long-term antifungal therapy and surgical management. The 2016 Infectious Diseases Society of America (IDSA) guidelines recommend amphotericin B with or without the addition of flucytosine or high-dose echinocandins (micafungin, caspofungin) as the initial therapy for Candida native valve and prosthetic valve endocarditis. Following this initial therapy, long-term therapy with fluconazole (400–800 mg per day) is recommended to ensure clearance of fungemia [20]. In addition to medical therapy, valvular replacement is also recommended, with continued antifungal therapy with fluconazole for at least six weeks following surgery or even longer in those patients with perivalvular abscesses for native valve endocarditis. Chronic suppressive therapy with daily high-dose fluconazole is recommended for patients with prosthetic valve endocarditis [20]. For those patients who are high-risk surgical candidates, long-term daily suppressive therapy with fluconazole in doses of 400–800 mg is recommended [20].
One of the challenges to definitive treatment in cases of Candida endocarditis, particularly with C. parapsilosis, is the increased risk of recurrence, which is most often due to inadequate clearance of fungemia (resulting in persistent fungemia) and the use of inappropriate antifungal therapy [21]. C. parapsilosis fungemia has been identified as a specific risk factor for the recurrence of endocarditis, as demonstrated in a retrospective case-control study by Munoz et al, mainly attributed to its ability to form biofilms [22]. Biofilms impede the therapeutic actions of antifungal agents, rendering organisms relatively resistant to antimicrobial agents [23]. Antimicrobial sensitivities obtained in our case revealed that the C. parapsilosis was sensitive to the first-line antifungal therapies used in her treatment. Therefore, the persistent fungemia and relapsing endocarditis encountered in our case is likely the result of inadequate clearance of the organism due to its biofilm production, as supported in the literature.
One of the challenges experienced in this case is the limited evidence-based guidance on managing persistent Candidemia despite appropriate antifungal therapy and recurrent C. parapsilosis endocarditis, as seen in our case. Notably, recurrent aortic valve infections caused by C. parapsilosis are associated with high morbidity and mortality rates. The mortality rate of C. parapsilosis endocarditis approaches 40%, necessitating a comprehensive understanding of this pathogen and its propensity for recurrence [18, 24].