Prosthetic Valve Endocarditis Due to Candida Tropicalis Complicated by Multiple Pseudoaneurysms

Infection

Case Report

Prosthetic Valve Endocarditis Due to Candida Tropicalis Complicated by Multiple Pseudoaneurysms K. Zedtwitz-Liebenstein, H. Gabriel, B. Willinger, H. Ehringer, P. Polterauer, W. Graninger

Abstract Candida endocarditis is an unusual but severe complication caused by Candida albicans or other fungal species. We describe a case of prosthetic valve endocarditis due to Candida tropicalis, complicated by multiple pseudoaneurysms.

Key Words Heart valve replacement · Endocarditis · Candida tropicalis · Multiple pseudoaneurysms Infection 2001; 29: 177-179 DOI 10.1007/s15010-001-9170-9

Introduction Candida endocarditis may be a serious complication of cardiac surgery. We report a case of Candida tropicalis endocarditis in a patient after prosthetic aortic valve replacement.

Case Report In a 46-year-old man suffering from aortic valve stenosis, valve replacement was performed with an aortic homograft. Postoperatively the patient improved rapidly (discharge 9 days later). One month later the patient developed signs of infection with fever and night sweats. Laboratory parameters revealed a C-reactive protein value of 14.5 mg/dl and leukocytosis with 13.5 G/l. A transesophageal echocardiography showed vegetations on the homograft and a suspect pseudoaneurysm of the ascending aorta. Because of this life-threatening situation it was necessary to replace the homograft in the aortic valve position immediately and to implant a vascular prosthesis in the ascending aorta. Meanwhile, blood cultures taken 2 days before the operation and cultures of the operated valve revealed growth of C. tropicalis. Therapy with flucytosine (2.5 g three time a day) and fluconazole (800 mg once a day) was started. No response with regard to fever and C-reactive protein was observed within 7 days and therefore, antifungal therapy was changed to conventional amphotericin B (1 mg/kg). The serum was positive for Candida antibodies (LD-Diagnostics, Heiden, Germany) and Candida antigen (Candtec®, Ramco, USA) at titers of 1 : 2,560 and 1 : 4, respectively. Subsequent controls showed increasing levels of antibodies (1 : 5,120 after 20 days; 1 : 10,240 after 37 days) while the antigen

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test was negative. Meanwhile, susceptibility testing showed the isolate to be susceptible to amphotericin B, fluconazole (MIC 1 µg/ml, evaluated by the microdilution method with casidone medium) and flucytosine.While receiving amphotericin B (1 mg/kg/day), the patient recovered slowly during the following 45 days. Eight weeks later thrombosis of the right brachial vein and mycotic pseudoaneurysms were detected in the right brachial artery and right axillary artery. The resection of the pseudoaneurysm necessitated a venous axillo-brachial bypass using a saphenous vein. Because of compression of the brachial plexus, neurolysis of the nervus medianus, musculocutaneus and ulnaris was necessary. While searching for aneurysms at other locations, occlusion of both upper femoral arteries was found by digital subtraction angiography. The pseudoaneurysms in the left and right upper femoral arteries were no longer detectable after 3 and 4 months, respectively. Echocardiography and blood cultures, initially carried out at monthly intervals, did not reveal relapses within 4 years.

Discussion Candida endocarditis was first described by Friedman in 1939 and is a serious complication of cardiac surgery. Around 0.1% of all heart valve replacements were complicated by fungal endocarditis. Candida spp. were responsible in 33–44% of patients [1]. Predisposing conditions, apart from cardiac surgery, are long-term therapy with antibiotics and corticosteroids, prolonged intravenous catheter and

K. Zedtwitz-Liebenstein (corresponding author), W. Graninger Dept. of Internal Medicine I, Division of Infectious Diseases, University Hospital of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria¸ Phone: (+43/14) 04004-440, Fax: -418, e-mail: [email protected] H. Gabriel Division of of Cardiology Internal Medicine II, University Hospital of Vienna, Vienna, Austria B. Willinger Division of Clinical Microbiology, Dept. of Hygiene, University Hospital of Vienna, Vienna, Austria H. Ehringer Division of Angiology, Dept. of Internal Medicine II, University Hospital of Vienna, Vienna, Austria P. Polterauer Dept. of Surgery, University Hospital of Vienna, Vienna, Austria Received: November 25, 1999 • Revision accepted: March 2, 2001

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heroin addiction [1–4]. Even with early diagnosis the prognosis is poor. A mortality rate of 80% has been reported in patients with fungal infections who are not treated surgically [5, 6]. Preexisting valvular abnormalities are crucial for the development of human fungal endocarditis, such as previous bacterial endocarditis, rheumatic heart disease or valve repair. The case described here illustrates many characteristic clinical features of candidal endocarditis. Without surgery, massive and fatal embolization occurs in 68–85% of cases [1, 5, 6]. In bacterial endocarditis the rate is lower, 17–43% [5, 8–10]. In 1885, Osler first described mycotic aneurysms resulting from septic emboli in bacterial endocarditis [11]. Mycotic aneurysms of the aorta represent rare but lifethreatening lesions. The first report of peripheral mycotic embolization was published by Zimmermann in 1950. Between 1950 and 1981, 44 cases of peripheral mycotic embolization were reported in the English literature, 21 with Candida spp. and 23 with Aspergillus spp. Only four patients had C. tropicalis. Mycotic aneurysms, probably caused by embolization of arteries to the vasa vasorum, may appear after both fungal and bacterial endocarditis [8, 12]. The Mayo Clinic, USA, has reported mycotic aneurysms at a frequency of 2% in bacterial endocarditis, while the incidence in fungal endocarditis is higher [13]. The high frequency of fatal embolization is partly explained by the fact that most publications on fungal endocarditis are based on diagnosis postmortem [14–16]. In the review by McLeod and Remington from 1978 [5], 19% of fungal infection episodes were preceded by bacterial endocarditis. The detection of antibodies in patients with Candida infection is of limited use. The antibody test does not usually distinguish between active and past infections and in immunocompromised patients, particularly those with opportunistic mycoses, antibodies may not be detectable. The Cand-Tec antigen assay has some limitations. Many investigators suggest that the test should be considered positive only when the titer is 1 : 4 or greater. The reported specificity and sensitivity of the Cand-Tec assay vary from 47.5–98% and from 19–91%, respectively [7, 17–19]. Regarding recommenations for treatment, historical reviews are of limited use because of low numbers of patients, patient group heterogeneity and lack of long-term followup information.Amphotericin B is still considered to be the most effective drug for most types of systemic fungal infection. The optimal length of treatment and the total dose necessary to cure patients with Candida endocarditis are unknown, but treatment periods of at least 8 weeks have been recommended [20, 21]. A total dose of between 2–3 g (50 mg/kg) is advocated, based upon the fact that survivors had usually received this amount. Combined therapy with amphotericin B and flucytosine has been shown to be superior to monotherapy in Can-

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dida endocarditis [22]. Newer azole drugs like fluconazole have been used for many types of fungal infection, but the experience in fungal endocarditis is limited at present [23]. A combination of surgery with debridement, valve replacement and antifungal therapy offers the best outcome, with an immediate mortality of 50% [24].

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