A case of recurrent Candida parapsilosis prosthetic valve endocarditis: Cure by medical treatment alone

Case Reports 8 Decker CF, Tarver JH, Murray DF, Martin GJ. Prolonged concurrent use of ganciclovir and foscarnet in the treatment of polyradiculopathy due to cytomegalovirus in a patient with AIDS. Clin Infect Dfs 1994; 19: 548-549. 9 Peters M, Timm U. Schtirmann D, Pohle HD, Ruf B. Combined and alternating ganciclovir and foscarnet in acute and maintenance therapy of human immunodeficiency virus-related cytomegalovirus encephalitis refractory to ganciciovir alone. Clin Invest 1992; 70: 456-458.

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10 Centers for Disease Control. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992; 41: 1-19. 11 Holland NR, Prover C, Mathews VP, Glass JD, Forman M, McArthur JC. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS). Neurology 1994; 44: 507-514.

A Case of Recurrent Candida parapsilosis Prosthetic Valve Endocarditis: Cure by Medical Treatment Alone T. L e j k o - Z u p a n c 1 a n d M. Ko~elj 2 XDepartment of Infectious Diseases and 2Department of Cardiovascular Diseases, Medical Centre Ljubl]ana, Japljeva 2, 1000 Ljubljana, Slovenia A patient with recurrent fungal endocarditis on prosthetic mitral valve is presented. Candida parapsilosis was the causative agent. The patient was treated medically with conventional amphotericin during the first episode. W h e n the disease recurred conventional amphotericin B was used again, but had to be stopped because of severe side effects. Treatment was continued with amphotericin B colloidal dispersion, followed by fluconazole for 8 months. The patient is healthy 16 months after discontinuation of fluconazole. Medical treatment of fungal endocarditis on prosthetic valves can be successful in selected cases.

Introduction Infective endocarditis due to Candida parapsilosis accounts for a significant proportion of cases of fungal endocarditis. Of the cases reported, 30% involved prosthetic valves. With the combined medical/surgical treatment, the survival rate of C. parapsilosis endocarditis is 50-64%. 1 Medical treatment of fungal endocarditis is rarely successful', it is particularly ineffective if infection involves prosthetic valves. Fungal endocarditis is therefore considered an absolute indication for valve replacement surgery, which, however, is sometimes not possible. 2 We report on a patient with recurrent prosthetic valve endocarditis due to C. parapsilosis who was cured by medical treatment alone.

• Case Report The patient was a 62-year-old w o m a n with rheumatic stenosis of the mitral valve. She had undergone a closed commissurotomy 25 years previously, and 5 years later valvuloplasty of the mitral valve. In January 1992 a Starr Edwards mitral valve prosthesis was inserted. The postoperative course was complicated by prolonged febrile illness and congestive heart failure. A series of blood cultures were negative. Transthoracic echocardiography (TTE) revealed a new paravalvular mitral regurgitation, but transoesophageal echocardiography (TEE) disclosed a small vegetation at the atrial side of the sewing

*Address correspondence to: T. Lejko-Zupanc. Accepted for publication 15 October 1996.

ring of the Starr Edwards mitral prosthesis. Mitral regurgitation of moderate severity originated at the site of the vegetation. The patient received a course of empirical antibiotic therapy for suspected early postoperative endocarditis. She responded well to the therapy and was discharged in a fairly good condition. No embolic or other complications were seen at that time. A monoclonal spike in the g a m m a globulin region was demonstrated on protein electrophoresis. OthEr tests, including a bone marrow examination, did not confirm the diagnosis of plasmocytoma. A control TEE performed during the course of medical therapy showed diminution of the vegetation and lesser intensity of the mitral regurgitation. In October 1992 the patient was hospitalized again with a high-grade fever and signs of congestive heart failure. Candida parapsflosis was yielded by six blood cultures. A new paravalvular leak was discovered but no vegetations were seen on TEE and TTE. Because the patient was considered a poor surgical risk, replacement of the valve was not considered. She was treated with amphotericin B, the cumulative dosage being 1990 mg. The only complication of the therapy was a moderate rise in serum urea and creatinine. A monoclonal spike on serum protein electrophoresis persisted, but no other signs of plasmocytoma were noted. At discharge from the hospital the patient was afebrile and free of signs of active infection or cadiac failure. After a period of good health she was hospitalized again in October 1993 with more pronounced signs of congestive heart failure than before. Candida parapsilosis was isolated from the blood cultures. The therapy with amphotericin B was reinstituted, but because of its severe side effects the patient was switched to amphotericin B colloidal dispersion (ABCD). On TTE a I cm long, mobile vegetation at the ventricular side of

Case Reports

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Table I. Clinical characteristics of medically treated patients with recurrent C. parapsilosis endocarditis. Reference Age, sex Type of prosthesis Time after operation Echocardiogram (first episode) Treatment Time before relapse Treatment Treatment with fluconazole

Isalska et al. 4 37, female Star Edwards mitral 16 weeks inconclusive Amphotericin B (2.050 mg) 6 months Amphotericin B plus Flcytosin 100 mg (continued)

Zahid et aI. s 48, male Bjork Shiley mitral 11 months no vegetations Amphotericin B (1.980 mg) 28 months Amphotericin B (3.010 rag) 400 mg, 30 months (continued)

the mitral valve ring was seen. Paravalvular regurgitation was mild and originated at the same site as a year before. No vegetations were seen on the atrial side of the mitral valve ring. The course of the disease was complicated by a septic infarct of the spleen and a small embolic infarct iri the right eye. The patient refused the operation. She received a total of 2 0 0 0 r a g of amphotericin B and 1 5 0 0 r a g of amphotericin B colloidal dispersion. The therapy was switched to oral fluconazole in a close of 400 mg per day for 2 weeks. She continued on a dose of l O 0 m g per day for 8 months without any side effects. The monoclonal spike on protein electrophoresis disappeared at the time of discharge from the hospital. She remains healthy 16 months after discontinuation of therapy.

Discussion Fungal endocarditis represents one of the absolute indications for surgery; however, removal of the infected valve is not always possible. In our patient, the course of the disease was prolonged with a relapse 8 months after the first episode. Late recurrences of fungal endocarditis are described even several months after the apparently successful t r e a t m e n t ] In our patient another episode occurred 10 months after cessation of therapy, and in the interim she had no symptoms indicating ongoing infection. Because the patient suffered only a few clinically unimportant embolic complications, and as she had only a small vegetation, we did not insist on removing the valve. To our knowledge, this is the third case of medically cured recurrent C. parapsilosis endocarditis of the prosthetic valve reported to date. The data on patients are presented in Table I. It should be pointed out that vegetations were found only in our patient, and that none of the patients had bulky vegetations considered to be typical of fungal endocarditis. 6 In all three cases the disease ran a mild course. Our patient had unusual echocardiographic findings. On relapse, the vegetation appeared only at the ventricular side of the valve ring, which is a most u n c o m m o n location. In contrast to the other two patients who were continued on fiuconazole, our patient has been without therapy for 16 months now. The dosage of fluconazole was

Our patient 62, female Starr Edwards mitral 9 months new paravalvular leak Amphotericin B (1.990 mg) 10 months Amphotericin B (2.000 rag), followed by ABeD (1.500 mg) 100 mg, 8 months

lower than in other two cases, and we presume that the disease was probably cured by the second course of amphotericin B, followed by ABCD. We decided to use ABCD because of the rise in serum blood urea nitrogen and creatinine and persistent hypokalaemia. The patient had severe rigors after receiving the first dosage of ABCD, but afterwards she tolerated the treatment very well. At discharge all laboratory parameters were normal. The efficacy of ABCD in treating fungal endocarditis has not yet been confirmed, but the drug should be investigated because of its lesser toxicity and its potential of achieving higher cumulative dosage. 7'8 Prolonged therapy with fluconazole caused no untoward side effects, and was well tolerated by the patient. It should probably be recommended as suppressive treatment after cessation of amphotericin B. Despite the limited virulence of C. parapsilosis compared to other candida species, the treatment of C. parapsilosis endocarditis remains surgical. Yet we believe that in selected cases, particularly in patients with few complications and small vegetations, medical treatment should be tried first.

References 1 Weems J]. Candida parapsilosis: epidemiology, pathology, clinical manifestations and antimicrobial susceptibility. Clin lnfect Dis 1992; 14: 756-766. 2 Alsip SG, Blackstone EH, KirldinJW, Cobbs CG. Indications for cardiac surgery in patients with active infective endocarditis. Am f Med 1985; 78(Suppl. 6B): 138-148. 3 Johnston PG, Lee J, Domanski M e t al. Late recurrent Candida endocarditis. Chest 1991; 99: 1531-1533. 4 Isalska BJ, Stanbridge TN. Fluconazole in the treatment of candidal prosthetic valve. BMJ 1988; 297: 178-179. 5 Zahid MA, Klotz SA, Hinton DR. Medical treatment of recurrent candidemia in a patient with probable Candida parapsflosis prosthetic valve endocarditis. Chest 1994; 105: 1596-1598. 60beid AI, eds. Echocardiograph9 in clinical practice. Philadelphia: Lippincott, 1992: 170-207. 70ppenheim BA, Herbrecht RI Kusne S. The safety and efficacy of amphotericin B colloidal dispersion in the treatment of invasive mycoses. Clin Infect Dis 1995; 21: 1145-1153. 8 Fromtling RA. Amphotericin B cholesterol sulfate complex (Colloidal dispersion). Drugs of the Future 1993; 18: 303-306.