Challenges in Diagnosing and Treating Fungal Endocarditis: A Case Report of Recurrent Candida Endocarditis in a Hemodialysis Patient

Abstract

Fungal endocarditis (FE) is a rare yet life-threatening condition, especially in hemodialysis (HD) patients with indwelling long-term catheters. Symptoms often overlap with non-fungal infective endocarditis, making diagnosis difficult. As FE incidence increases, healthcare providers face challenges in diagnosing and managing this severe condition. Early suspicion of FE is crucial for patients with long-term catheters. We reported a 23-year-old male with end-stage renal disease (ESRD) on HD that developed FE affecting the tricuspid valve, requiring valve replacement and anti-fungal medication. Despite these interventions, he had recurrent Candida prosthetic endocarditis (CPE). Currently, he is receiving anti-fungal medication, with plans for a third surgery.

1. Introduction

FE is a rare and life-threatening infection, accounting for approximately 1–2 % of infective endocarditis (IE) cases with mortality rates of 46.6%–59% [1]. In HD patients, FE incidence is 50–180 times higher, particularly in those with indwelling long-term catheters [2,3]. Consequently, the rise of FE is anticipated to escalate among HD patients, posing new challenges for healthcare providers. FE patients may present with nonspecific symptoms such as fatigue, weight loss, diaphoresis, and that develop over weeks to months and be indistinguishable from IE [4]. Echocardiography and microbiological assays, including blood cultures and PCR techniques, play a diagnostic role [4,5]. In addition, radionuclide imaging, particularly 18F-fluorodeoxyglucose positron emission tomography/computed tomography, is used in the assessment [6]. Combined anti-fungal and surgical therapy improve survival [5,7]. Congestive heart failure and septic embolism are the primary causes of death in FE cases.

2. Case presentation

A 23-year-old male with hypertension, type 1 diabetes, rheumatic heart disease, and ESRD, underwent hemodialysis biweekly via a right jugular permacath inserted 4 years ago. In 2021, he presented with a high fever (39.5 °C) without other symptoms. Examination revealed a systolic murmur over the tricuspid valve, suggesting IE. Initial blood cultures were negative, and empirical treatment with moxifloxacin and vancomycin began. Later, blood cultures were positive for Candida. Transthoracic echocardiography (TTE) showed a mass on the septal leaflet of the tricuspid valve (Fig. 1), with normal LV dimension, EF 60%, no wall motion abnormalities, moderate to severe tricuspid regurgitation (TR), and pulmonary artery systolic pressure (PASP) of 50 mmHg. Follow-up echocardiography showed the mass was increased in size, highly mobile with another mass within RA, and Increased TR. He received a 6-week course of fluconazole and underwent tricuspid valve replacement with a tissue valve. Two months later, during dialysis via left femoral permacath, he developed a low-grade fever. Blood cultures and echocardiography were negative, he was discharged on fluconazole for eight weeks and had weekly blood cultures. The patient was admitted four times for evaluation of possible FE due to persistent high fever; however, blood cultures and echocardiography were negative. He received another course of fluconazole for two weeks and continued dialysis via right femoral permacath.

Fig 1.

Echocardiogram images show a 2.3 × 0.8 cm mass attached to the native tricuspid leaflets.

After six months, he returned with a two-month fever (39.6 °C) and no other symptoms. Examination revealed a pan-systolic murmur and hepatosplenomegaly. Lab results indicated hemolytic anemia consistent with microangiopathic hemolytic anemia (MAHA) due to the prosthetic valve. Blood cultures were positive for Candida parapsilosis, and TTE showed severe TR with a mass on the bioprosthetic valve (Fig. 2). He received a three-week course of fluconazole, then the blood C/S was sensitive to caspofungin and resistant to fluconazole so they stopped fluconazole and started caspofungin, had a second prosthetic tricuspid valve replacement, followed by a three-week course of caspofungin.

Fig 2.

RV focus image shows a 1.8 × 0.9 cm mass attached to the bioprosthetic tricuspid leaflets.

Eight months later, he presented again with a month-long fever (39 °C). Blood cultures identified Candida parapsilosis, and TTE showed a 2.3 cm mass in the prosthetic tricuspid valve (Fig. 3), moderate mitral regurgitation, and trace aortic regurgitation. He received fluconazole and caspofungin, with plans for anti-fungal lifelong alongside tricuspid valve replacement.

Fig 3.

The apical view shows vegetation attached to the bioprosthetic tricuspid leaflets.

3. Discussion

FE, a rare and often fatal complication of fungemia, poses diagnostic and therapeutic challenges [5]. Candida species cause about 50% of cases, affecting native valves, prosthetic valves, the endocardial surface, and cardiac devices. Diagnosis is often delayed due to negative blood cultures, especially in Aspergillus infections [6]. This delay and routine antibacterial treatments contribute to 10–75% mortality rates [8]. In our case, negative blood cultures led to empirical antibacterial therapy with vancomycin and moxifloxacin. A subsequent diagnosis of candidiasis led to a tailored treatment approach with anti-fungal drugs and valve replacement, improving their clinical status.

FE pathogenesis involves fungi entering the bloodstream and adhering to the endocardium through fungal surface proteins and int1p proteins in Candida species. This attachment leads to growth, tissue invasion, and damage from initial colonization [6]. The FE risk increases in ESRD patients undergoing hemodialysis due to factors like indwelling catheters, valve calcification, dialysis-related bacteremia, antibiotic usage, compromised immunity due to uremia, prior cardiac procedures, and associated co-morbidities [9]. Echocardiography is crucial in diagnosing infective endocarditis, identifying large, predominantly left-sided lesions (with bilateral lesions often in immunocompromised individuals) and non-valvular lesions or abscesses at the valve ring [6]. Radionuclide imaging methods like 18F-fluorodeoxyglucose PET/CT can provide valuable additional information about fungal infection extent and location [10].

Microbiological tests, such as API 20C and Chromogenic media, are essential in identifying Candida species for anti-fungal therapy [8]. Non-culture-based approaches, including mannan antigen and antibody testing, polymerase chain reaction (PCR), real-time PCR, and metagenomic next-generation sequencing (mNGS), offer potential for earlier FE diagnosis. More research is needed to establish their reliability [8]. Meta-analyses show combination anti-fungal therapy is superior to monotherapy for prosthetic and non-prosthetic candida endocarditis, prompting guidelines to recommend valve replacement with anti-fungal treatment for better outcomes [8].

FE and CPE mortality is higher with anti-fungal therapy compared to surgery plus anti-fungal medications. Consequently, guidelines from the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommend valve replacement along with anti-fungal treatment using amphotericin B with or without 5-flucytosine, followed by long-term fluconazole therapy. For those unsuitable for surgery, lifelong fluconazole is advised to maintain fungal suppression and prevent recurrences [8]. Echinocandins, especially caspo-fungin, show efficacy against Candida biofilms, with evidence suggesting improved outcomes when administered early [8]. Switching from hemodialysis to peritoneal dialysis (PD) has shown significant benefits for hospitalized ESRD patients with FE, reducing in-hospital mortality from 55.5% to 8.3% [8] by minimizing vascular access manipulation, thus lowering the risk of fungal dissemination.

4. Conclusion

Early detection of FE is difficult due to its subtle, nonspecific symptoms that often overlap with other infections. A heightened awareness among clinicians, particularly in patients undergoing hemodialysis, is crucial for early detection due to the increased risk in this population. The recommended treatment for FE combines anti-fungal medications with valve replacement. PD should be considered in hemodialysis patients to reduce recurrence risk. Further studies are needed to develop novel methods for early detection and minimizing recurrence, ultimately improving the management of FE.

Abbreviation list

FE

Fungal endocarditis

IE

Infective endocarditis

CPE

Candida prosthetic endocarditis

HD

Hemodialysis

ESRD

End-stage renal disease

TTE

Thoracic echocardiography

MAHA

Microangiopathic hemolytic anemia

PCR

Polymerase chain reaction

mNGS

Metagenomic next-generation sequencing

IDSA

Infectious Diseases Society of America

ESCMID

The European Society of Clinical Microbiology and Infectious Diseases

PD

Peritoneal dialysis