Candida parapsilosis Endocarditis: Medical and Surgical Cure EVA MARTIN, M.D.; STEPHEN J. PANCOAST, M.D.; and HAROLD C. NEU, M.D. Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University; New York, New York C A N D I D A ENDOCARDITIS has been associated with open
heart surgery (1), prolonged intravenous therapy (such as hyperalimentation, antibiotics), and heroin addiction (2). The commonest species has been Candida parapsilosis, in approximately 50% of cases (3-5). Treatment with either antifungal agents or surgery alone has resulted in a poor survival rate (7% to 14.5%), whereas combined medical and surgical therapy has had a more promising outlook (55% to 80% survival rate) (6). Adequate medical follow-up of treated survivors of Candida endocarditis has been poor (7, 8). We report a surviving patient who had proven Candida parapsilosis aortic valve endocarditis with surgically confirmed cure at 5l/2 years after medical and surgical intervention. A 30-year-old male former heroin addict was admitted to Columbia-Presbyterian Medical Center in March 1973 complaining of fatigue, muscle pains, dyspnea on exertion, orthopnea, and a 20.4-kg weight loss. The physical examination showed a temperature of 38.8 °C; blood pressure, 120/30 mm Hg; and pulse, 130/min. Palmar petechiae, bilateral basilar 3 7 0
December 1979 • Annals of Internal Medicine • Volume 91 • Number 6
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
rales, and splenomegaly were noted. Cardiovascular examination revealed a grade III/VI systolic ejection murmur and a diastolic, decrescendo murmur along the left sternal border with radiation to the apex. Laboratory studies showed a hematocrit of 28.5%, and leukocyte count of 3000 cells/mm3. The erythrocyte sedimentation rate was 26 mm/h (Westergren). Seven blood cultures grew Candida parapsilosis. Therapy with amphotericin B and flucytosine was begun, and the patient underwent surgery 4 d after admission. At surgery the aortic valve had large vegetations loosely adherent to the noncoronary and left coronary cusps, which projected into the ventricle and separated spontaneously on manipulation. The vegetations consisted of masses of fibrin containing large numbers of Candida with giant pseudomycelia characteristic of this Candida species (Figure 1). The patient had a complicated 2-month postoperative course, receiving 70 mg of amphotericin every other day and 12 g of flucytosine each day. He received a total of 1340 mg of amphotericin B and 396 g of flucytosine. During the next several months 20 postoperative blood cultures were negative for fungi and bacteria. Five and a half years after successful valve replacement the patient developed complaints identical to those of thefirstadmission. He had not taken any narcotics in the intervening 5year period. Physical examination revealed a grade V/VI systolic ejection murmur over the entire precordium. The hematocrit value was 26.8%; lactic dehydrogenase, 3000 U; bilirubin, 3.1 mg/dL; and hapatoglobin, absent. Blood cultures were sterile, and Candida serology studies were negative. The patient underwent valve replacement for ball variance. No vegetations were observed on the valve, but degeneration of fabric covering the struts and a large pannus arising from the valve seat and partially occluding one of the coronary ostia was noted. Cultures and microscopic examination of the prosthetic valve and pannus were negative. The patient recovered without complications. Previously reported cures of Candida endocarditis have been based on the absence of clinical findings and negative blood cultures. In many instances the original diagnosis would be in dispute because it was based solely on isolation of Candida from several blood cultures. In reports of medical cures, positive blood cultures alone may not mean endocarditis, and thus even if surgery after medical therapy shows no evidence of fungal endocarditis, this cannot be assumed to represent a cure (5). In previously reported cases of fungal endocarditis treated medically and surgically where the diagnosis is not in doubt, limited and short follow-ups mean that how many patients of those who survived are cured long-term is unclear (7, 8). Although cases in which fungal endocarditis was medically treated have been reported, mortality has remained high without surgery because fungal endocarditis is characterized by the complications produced by bulky, friable valvular vegetations (that is, heart failure and major arterial embolization). Early surgical removal of these potentially lethal fungal aggregates is essential. Antifungal therapy alone may actually facilitate further embolization by destroying adherent viable mycotic colonies, making them less capable of withstanding turbulent flow patterns. Therefore, surgery is usually needed to remove large collections of valvular vegetations, using antifungal agents to eradicate any remaining microscopic foci of Candida. Because of the limited experience with Candida endocarditis of most groups and variation in host factors, establishing the effectiveness of any particular chemotherapeutic regimen is difficult. That this patient's vegetations were so loosely adherent as to spontaneously separate at surgery only underscores the need for surgery.
Figure 1 . Microscopic findings of the aortic valve vegetations. Overlying fibrin (A), yeast and pseudomycelia characteristic of Candida parapsilosis (B), and valvular tissue (C).
Until cases with proven disease and established longterm cures with medical therapy alone are reported, the combined medical and surgical approach to therapy of Candida endocarditis would be optimal. The present case demonstrates the effectiveness of the combined amphotericin-flucytosine and surgical approach (3, 4). This is in contrast to previously reported experience with Candida parapsilosis endocarditis, where, even with optimal combined medical and surgical treatment, the mortality approached 99% (7, 8). REFERENCES 1. S E E L I G MS, S P E T H CP, K O Z I N I N PJ, T S A C H D J I A N CL, T O N I
3. U T L E Y JR, M I L L S J, H U T C H I N S O N JC, E D M U N D S LH J R , SANDERSON
RG, R O E BB. Valve replacement for bacterial and fungal endocarditis: a comparative study. Circulation. 1973;48 (suppl III):III 42-9. 4. T U R N I E R E, K A Y J H , B E R N S T E I N S, M E N D E Z AM, Z U B I A T E P. Surgi-
cal treatment of Candida endocarditis. Chest. 1975;67:262-8. 5. M A Y R E R AR, B R O W N A, W E I N T R A U B R A , R A G N I M, POSTIC B. Suc-
cessful medical therapy for endocarditis due to Candida parapsilosis: a clinical and epidemiologic study. Chest. 1978;73:546-9. 6. G O E N E N M, R E G N A E R T M, J A U M I N P, C H A L A N T C, T R E M O U R O U X J.
A case of Candida albicans endocarditis 3 years after an aortic valve replacement. / Cardiovasc Surg. 1977;18:391-6. 7. P R E M S I N G H N, K A P I L A R, T E C S O N F, S M I T H LG, L O U R I A DB. Candi-
da endocarditis in two patients. Arch Intern Med. 1976;136:208-12. 8. R U B I N S T E I N E, N O R I E G A ER, SIMBERKOFF MS, H O L Z M A N R, R A H A L
JJ. Fungal endocarditis: analysis of 24 cases and review of the literature. Medicine (Baltimore). 1975;54:331-4. ©1979 American College of Physicians Brief Reports
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
EF,
GOLDBERG P. Patterns of Candida endocarditis following cardiac surgery: importance of early diagnosis and therapy. Prog Cardiovasc Dis. 1974;17:125-60. 2. STIMMEL B, DONOSO E, D A C K S. Comparison of infective endocarditis in drug addicts and non-drug users. Am J Cardiol. 1973;32:924-32.
871
heart surgery (1), prolonged intravenous therapy (such as hyperalimentation, antibiotics), and heroin addiction (2). The commonest species has been Candida parapsilosis, in approximately 50% of cases (3-5). Treatment with either antifungal agents or surgery alone has resulted in a poor survival rate (7% to 14.5%), whereas combined medical and surgical therapy has had a more promising outlook (55% to 80% survival rate) (6). Adequate medical follow-up of treated survivors of Candida endocarditis has been poor (7, 8). We report a surviving patient who had proven Candida parapsilosis aortic valve endocarditis with surgically confirmed cure at 5l/2 years after medical and surgical intervention. A 30-year-old male former heroin addict was admitted to Columbia-Presbyterian Medical Center in March 1973 complaining of fatigue, muscle pains, dyspnea on exertion, orthopnea, and a 20.4-kg weight loss. The physical examination showed a temperature of 38.8 °C; blood pressure, 120/30 mm Hg; and pulse, 130/min. Palmar petechiae, bilateral basilar 3 7 0
December 1979 • Annals of Internal Medicine • Volume 91 • Number 6
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
rales, and splenomegaly were noted. Cardiovascular examination revealed a grade III/VI systolic ejection murmur and a diastolic, decrescendo murmur along the left sternal border with radiation to the apex. Laboratory studies showed a hematocrit of 28.5%, and leukocyte count of 3000 cells/mm3. The erythrocyte sedimentation rate was 26 mm/h (Westergren). Seven blood cultures grew Candida parapsilosis. Therapy with amphotericin B and flucytosine was begun, and the patient underwent surgery 4 d after admission. At surgery the aortic valve had large vegetations loosely adherent to the noncoronary and left coronary cusps, which projected into the ventricle and separated spontaneously on manipulation. The vegetations consisted of masses of fibrin containing large numbers of Candida with giant pseudomycelia characteristic of this Candida species (Figure 1). The patient had a complicated 2-month postoperative course, receiving 70 mg of amphotericin every other day and 12 g of flucytosine each day. He received a total of 1340 mg of amphotericin B and 396 g of flucytosine. During the next several months 20 postoperative blood cultures were negative for fungi and bacteria. Five and a half years after successful valve replacement the patient developed complaints identical to those of thefirstadmission. He had not taken any narcotics in the intervening 5year period. Physical examination revealed a grade V/VI systolic ejection murmur over the entire precordium. The hematocrit value was 26.8%; lactic dehydrogenase, 3000 U; bilirubin, 3.1 mg/dL; and hapatoglobin, absent. Blood cultures were sterile, and Candida serology studies were negative. The patient underwent valve replacement for ball variance. No vegetations were observed on the valve, but degeneration of fabric covering the struts and a large pannus arising from the valve seat and partially occluding one of the coronary ostia was noted. Cultures and microscopic examination of the prosthetic valve and pannus were negative. The patient recovered without complications. Previously reported cures of Candida endocarditis have been based on the absence of clinical findings and negative blood cultures. In many instances the original diagnosis would be in dispute because it was based solely on isolation of Candida from several blood cultures. In reports of medical cures, positive blood cultures alone may not mean endocarditis, and thus even if surgery after medical therapy shows no evidence of fungal endocarditis, this cannot be assumed to represent a cure (5). In previously reported cases of fungal endocarditis treated medically and surgically where the diagnosis is not in doubt, limited and short follow-ups mean that how many patients of those who survived are cured long-term is unclear (7, 8). Although cases in which fungal endocarditis was medically treated have been reported, mortality has remained high without surgery because fungal endocarditis is characterized by the complications produced by bulky, friable valvular vegetations (that is, heart failure and major arterial embolization). Early surgical removal of these potentially lethal fungal aggregates is essential. Antifungal therapy alone may actually facilitate further embolization by destroying adherent viable mycotic colonies, making them less capable of withstanding turbulent flow patterns. Therefore, surgery is usually needed to remove large collections of valvular vegetations, using antifungal agents to eradicate any remaining microscopic foci of Candida. Because of the limited experience with Candida endocarditis of most groups and variation in host factors, establishing the effectiveness of any particular chemotherapeutic regimen is difficult. That this patient's vegetations were so loosely adherent as to spontaneously separate at surgery only underscores the need for surgery.
Figure 1 . Microscopic findings of the aortic valve vegetations. Overlying fibrin (A), yeast and pseudomycelia characteristic of Candida parapsilosis (B), and valvular tissue (C).
Until cases with proven disease and established longterm cures with medical therapy alone are reported, the combined medical and surgical approach to therapy of Candida endocarditis would be optimal. The present case demonstrates the effectiveness of the combined amphotericin-flucytosine and surgical approach (3, 4). This is in contrast to previously reported experience with Candida parapsilosis endocarditis, where, even with optimal combined medical and surgical treatment, the mortality approached 99% (7, 8). REFERENCES 1. S E E L I G MS, S P E T H CP, K O Z I N I N PJ, T S A C H D J I A N CL, T O N I
3. U T L E Y JR, M I L L S J, H U T C H I N S O N JC, E D M U N D S LH J R , SANDERSON
RG, R O E BB. Valve replacement for bacterial and fungal endocarditis: a comparative study. Circulation. 1973;48 (suppl III):III 42-9. 4. T U R N I E R E, K A Y J H , B E R N S T E I N S, M E N D E Z AM, Z U B I A T E P. Surgi-
cal treatment of Candida endocarditis. Chest. 1975;67:262-8. 5. M A Y R E R AR, B R O W N A, W E I N T R A U B R A , R A G N I M, POSTIC B. Suc-
cessful medical therapy for endocarditis due to Candida parapsilosis: a clinical and epidemiologic study. Chest. 1978;73:546-9. 6. G O E N E N M, R E G N A E R T M, J A U M I N P, C H A L A N T C, T R E M O U R O U X J.
A case of Candida albicans endocarditis 3 years after an aortic valve replacement. / Cardiovasc Surg. 1977;18:391-6. 7. P R E M S I N G H N, K A P I L A R, T E C S O N F, S M I T H LG, L O U R I A DB. Candi-
da endocarditis in two patients. Arch Intern Med. 1976;136:208-12. 8. R U B I N S T E I N E, N O R I E G A ER, SIMBERKOFF MS, H O L Z M A N R, R A H A L
JJ. Fungal endocarditis: analysis of 24 cases and review of the literature. Medicine (Baltimore). 1975;54:331-4. ©1979 American College of Physicians Brief Reports
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
EF,
GOLDBERG P. Patterns of Candida endocarditis following cardiac surgery: importance of early diagnosis and therapy. Prog Cardiovasc Dis. 1974;17:125-60. 2. STIMMEL B, DONOSO E, D A C K S. Comparison of infective endocarditis in drug addicts and non-drug users. Am J Cardiol. 1973;32:924-32.
871
