Candida parapsilosis endocarditis ın a patient with liver transplantation

INTRODUCTION

Infective endocarditis (IE) is caused by viral, bacterial or fungal pathogens, with high morbidity and mortality. While its incidence in the community is 6/100 000 person/year; its incidence in solid organ transplant (SOT) recipients rises to 1%–1.7%.¹ The incidence of IE does not change according to the transplanted organ.² Factors that increase the risk of IE are immunosuppression, prolonged hospitalization and intensive care unit stay, post-surgical complications, invasive procedures, nosocomial bloodstream infections, mediastinitis and poor nutritional status.³ It is suggested that SOT recipients undergo a detailed cardiac evaluation, especially for underlying heart valve pathologies, in the pre-transplant period due to the increased risk of IE. Fungal endocarditis is rare and is associated with severe complications with poor prognosis despite combined medical and surgical treatment.^3,4 Although Candida albicans is the most common fungal agent of this severe form of endocarditis, Candida parapsilosis is the most common non-albicans causative species. The diagnosis is made through echocardiography and multiple blood cultures.⁴ The incidence of this disease has increased in the past few decades, mainly due to advances in diagnostic approaches. We present a 17-year-old patient with C. parapsilosis endocarditis with vegetation on the prosthetic valve, who had been on immnoupressive drugs after liver transplantation.

THE CASE

A 17-year-old patient who had had a liver transplant was referred to our paediatric cardiovascular surgery ward with a diagnosis of right heart failure. He had had coronary artery bypass graft and aortic valve replacement operation in 2021. He came to the outpatient clinic with complaints of fever, weakness, nausea and vomiting. On physical examination, he had pallor, dyspnoea and tachycardia. His fever was 38 °C and a grade 2/6 systolic ejection murmur was detected on auscultation. Laboratory tests showed increased acute phase reactants, procalcitonin and troponin levels. Blood cultures were obtained and prosthetic valve endocarditis treatment was started empirically, considering the presence of vegetation and micro abscesses in the echocardiography (Fig. 1) and transoesophageal echocardiography (TEE) of the patient. Candida parapsilosis was isolated from the blood cultures. Echocardiography demonstrated a 0.5×0.5 cm mass in the mitral valve, multiple micro abscesses in the tricuspid valve, and on both sides of the aortic valve. In the post-stress Tc99m myocardial perfusion GATED SPECT study, wall movements were observed to be within normal limits. Ejection fraction was calculated as 68%. Amphotericin B in a dose of 4 mg/kg/day was started based on the antifungal sensitivity test.

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FIG I.

Transoesophageal echocardiographic image of the patient

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There was no evidence of candida infection in the ophthalmology examination or on abdominal ultrasonography. The medical treatment was completed successfully and the patient was discharged to be followed in the outpatient clinic.

DISCUSSION

Fungal endocarditis is rare, about 2% of all IE cases, but it is associated with high mortality rates of above 50%. Candida spp. has been reported to be the cause of 53%–68% of fungal endocarditis cases. Şimşek-Yavuz et al. reported that 2.4% of all fungal IE cases in Turkey were due to Candida spp.5 C. parapsilosis, a rare fungal IE agent, has been reported in patients with predisposing risk factors such as intravenous drug use, immunosuppression, total parenteral nutrition, abdominal surgery, treatment with broad-spectrum antibiotics and previous valve disease or cardiac surgery.⁴ In this patient, we suspected IE and isolated C. parapsilosis from the blood cultures of the patient who had been on immunosuppressive drugs after liver transplantation and also had a prosthetic heart valve.

The clinical presentation of IE is variable and non-specific such as fever, shortness of breath, chest pressure, asthenia, altered mental status, new cardiac murmur or signs of acute or chronic heart failure. Peripheral embolic and/or haemorrhagic events are also common and may be the first and only symptoms of this disease.^4,5 IE should also be considered during the evaluation of fever of unknown origin. The diagnosis should be made according to the Duke criteria.⁶ Our patient had complaints of fever, fatigue, loss of appetite, shortness of breath, palpitation, nausea and vomiting at the time of admission to hospital.

Blood cultures are negative in 2%–40% of endocarditis cases, with some studies reporting negative blood cultures in up to 71% of cases.⁷ Blood cultures are positive in <50% of Candida endocarditis cases.⁸ Echocardiography plays an important role in detecting fungal endocarditis and should be done within the first 24 hours. The sensitivity of echocardiography is limited, particularly in prosthetic valve endocarditis, and therefore, a high index of suspicion is required to make the diagnosis to enable early initiation of therapeutic measures that can improve the prognosis. The aortic valve appears to be the most commonly involved valve, with 42.5% of endocarditis cases reported to occur in native valves.⁹ C. parapsilosis growth was observed in the blood culture, obtained in the febrile period of our patient.

Although successful results have been reported with medical therapy alone, some publications suggest a therapeutic approach combining antifungal agents and valve replacement operation to improve clinical outcomes. Surgical intervention is needed in 25%–53% of IE cases.⁷ Despite recent advances in diagnosis and treatment strategies and combined therapies, this disease carries a high risk of morbidity and mortality (mortality rate approximately 42%).^8,9 Since our hospital is a tertiary referral centre for heart diseases and cardiac surgery, we suspected IE considering his clinic presentation and predisposing factors. We did echocardiography and TEE immediately, C. parapsilosis was isolated from the blood culture and we presume that early diagnosis enabled the successful outcome.

The first choice antifungal in IE due to Candida spp. is amphotericin B or echinocandins with fungicidal activity. Echinocandins should be used in higher than normal doses. In patients with artificial valve IE due to Candida spp., mortality rates were lower in the group using liposomal amphotericin B for induction therapy, and surgery did not decrease mortality in this group. However, the fact that 41% of the strains causing IE were C. parapsilosis and the minimum inhibitory concentration (MIC) values of echinocandin in these strains, determined as 8 times higher than the MIC values of C. albicans (0.25 μg/ml v. 0.03 μg/ ml), may have contributed to this outcome. In other words, regimens containing amphotericin B should be preferred due to the high echinocandin MIC values, especially in C. parapsilosis. In the long-term treatment of fungal artificial valve IE, suppression therapy is initiated following induction therapy.^8,9