756
3. Venditti M, Posteraro B, Morace G, Marlino P: In vitro comparative activity of flueonazole and other antifungal agents against Blastoschizomyces capitatus. Journal of Chemotherapy 1991, 3: 13-15. 4. Surmont I, Vergauwen B, Marcelis L, Verbist L, Ver. hoef G, Boogaerls M"First report of chronic meningitis caused by Trichosporon beigelii. European Journal of Clinical Microbiology and Infectious Diseases 1990, 9: 226-229. 5. Arndt CAS, Walsh TJ, McCully CL, Balis FM, Pizzo PA, Poplack DG: Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. Journal of Infectious Diseases 1988, 157: 178-180. 6. Sugar AM, Saunders C: Oral fluconazole suppressive therapy of disseminated cryptococcosisin patients with acquired immunodeficiency syndrome. American Journal of Medicine 1988, 85: 481--489. 7. Maksymiuk AW, Thongprasert S, Hopfer R, Luna M, Fainstein V, Bodey GP-"Systemic eandidiasis in cancer patients. American Journal of Medicine 1984, 77, Supplement 4D: 20-27.
Long-Term Survival of a Patient with Prosthetic Valve Endocarditis due to Trichosporon beigelii J. M a r t i n e z - L a c a s a 1, J. Mafia 1., R. Niub61, G. R u f i 2, A. Saez 3, E Fern~indez-Nogu6s I
A case is described of a 49-year-old man with rheumatic aortic valve disease who developed endocarditis seven years after valvular replacement. Trichosporon beigelii was isolated from the blood, a peripheral thrombus, and the removed prothesis. After two valve prosthesis replacements and prolonged antifungal therapy, the patient survived for four years, but eventually died as a consequence of multiple septic complications due to the same organism. To the authors' knowledge, this is the longest survival time of any reported case of Trichosporon prosthetic valve endocarditis.
Trichosporon beigelii is a yeast that is known as the causative agent of white piedra, a fungal infection of the hair shaft (1).It was traditionally con1Department of Internal Medicine, 2Infectious Diseases Unit, and 3Department of Pathology, Hospital de Bellvitge "Prfnceps D'Espanya", Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
Eur. J. Clin. Microbiol. Infect. Dis.
sidered to be a non-invasive fungus, but in recent years several cases of fungemia and systemic infection in immunocompromised patients have been described (2). As far as we know, only six well documented and two possible cases of Trichosporon beigelii and Trichosporon capitaturn endocarditis have been previously reported in the literature (3-10). We describe a case of Trichosporon beigelii endocarditis in a patient who survived several years and developed multiple septic complications. Case Report. In January 1985, a 49-year-old man was admitted to our hospital because of fever. Seven years earlier a Carpentier-Edwards valve prothesis had been inserted due to double aortic lesion of rheumatic origin. Three weeks before admission he had had fever and pain in the left upper abdominal quadrant. On physical examination the patient appeared acutely ill and febrile, with an aortic regurgitation murmur and hepatosplenomegaly. The erythrocyte sedimentation rate was 52 mm, hemoglobin 11.4 g/100 ml, white blood cell count 12500/mm 3 with 2 1 % eosinophils, alkaline phosphatase 163 1U, and gamma globulin 22 g/l. An echocardiogram disclosed aortic prosthetic valve vegetations and a 99mTc sulfur colloid liver-spleen scan was normal. Blood samples were obtained for culture and empiric treatment with penicillin and streptomycin was started. However, the fever persisted and ten days after admission the patient complained of leg pain and his right leg was cold, with absence of popliteal and pedal pulses. A popliteal thrombus showing the presence of hyphae was removed surgically. Trichosporon beigelii grew in three blood cultures and the thrombus. Amphotericin B was given and the prothesis was replaced. Trichosporon beigelii was also isolated from the prosthetic valve vegetations. In vitro susceptibility tests showed the organism to be sensitive to amphotericin B (MIC 0.3 mcg/ml), and ketoconazole (MIC 4 mcg/ml), and resistant to 5-fluorocytosine (MIC 20 mcg/ml). After the operation the patient developed severe hepatic cholestasis and a liver biopsy demonstrated granulomatous hepatitis. Repeat blood cultures were negative and a complete course of 2.5 g of amphotericin B was administered for eight weeks. The patient improved and was discharged. In October 1985 he was readmitted because of fever and peripheral embolisms in the fingers and toes. Blood cultures were again negative and an echocardiogram did not show vegetations. The patient improved without any additional treatment. In March 1986 fever and the
Vol. 10, 1991
peripheral vascular disturbances reappeared. Trichosporon beigelii was again isolated in two blood cultures and a new prothesis replacement was carried out. The prosthetic valve culture was sterile, and a pacemaker was inserted due to atrioventricular block. A course of 2.5 g of amphotericin B was again administered followed by 400 mg oral ketoconazole per day. In March 1987, while he was receiving ketoconazole, fever and peripheral embolisms recurred; blood cultures were negative and an echocardiogram disclosed no vegetations. The eosinophil count was 1,080/ ram3. Ketoconazole was discontinued after ten months and the patient improved spontaneously. In May 1988 he complained of lumbar pain for several weeks. An x-ray of the lumbar spine, a vertebral technetium scan, and a CT scan of the lumbar spine showed osteolysis of the 3rd and 4th lumbar vertebrae; a needle aspiration was sterile. Bed rest and analgesic therapy were prescribed. Two months later, fever and peripheral embolisms in the toes reappeared. Three days after admission the patient had headache and decreased consciousness. A CT scan of the brain showed parietal hemorrhage and an arteriography disclosed multiple cerebral aneurysms. Surgery was performed with drainage of the hematoma and resection of several mycotic aneurysms; cultures were sterile. A new replacement of the aortic prothesis was considered too hazardous, and treatment with 2.5 g of amPbotericin B was readministered for the third time with a good clinical result. In April 1989 the patient complained of abdominal pain, vomiting and new peripheral vascular disturbances. Arteriography showed the presence of an embolus in the upper mesenteric artery. Oral fluconazole therapy (400 mg per day) was administered with some improvement. No tests of susceptibility to fluconazole could be carried out. One month later, while he was receiving flUconazole, Tr&hosporon beigelii was isolated in two blood cultures. The patient died a few days later with shock and fever. Post mortem examination disclosed an aortic prothesis with large Vegetations, and mukiple embolisms ~nd infarcts m the kidneys and brain. Trichosporon beigelii was isolated from both the prothesis and the kidney. Discussion. Trichosporon beigelii, also referred to as Trichosporon cutaneum, belongs to the family CryPtococcaceae. It is the etiologic agent of white piedra, an infection of the hair shafts. It is ocCasionally encountered among the normal flora of
757
Figure 1: Large vegetationson the prosthetic aortic valve.
Figure 2: Mcthenamine-silver stain of prosthetic valve vegetation showing branching mycelia[ elements (magnit'ication x 500). the skin, and also has been isolated from respiratory secretions, urine and stool of healthy persons (1). It is traditionally considered a nonpathogenic fungus. However, in the past 25 years several cases of disseminated infection in immunocompromised patients have been described (2). So far, however, only six well documented cases (3-8) and two possible cases (9, 10) of Tricho~poron endocarditis have been reported in the literature. Although neutropenia probably predisposes to disseminated infection in immunocompromised patients (2), most cases of endocarditis have been reported in patients with prosthetic valves (3, 4, 6, 8) or native valve involvement associated with parenteral drug addiction or peritoneovenous shunt (5, 7). The portal of entry of the organism is uncertain. The gastrointestinal tract, upper respiratory tract and endovascular catheter contamination have
758
often been implicated (10-12). In prosthetic valve endocarditis, previous surgery may play an important role due to possible skin colonization by Trichosporon beigelii in immunocompetent patients. Trichosporinosis may be difficult to diagnose because blood cultures may be repeatedly negative. Cultures of the prothesis or the endovascular material most often reveal the presence of Trichosporon (3-8).
Trichosporon spp. causing endocarditis have usually been sensitive to amphotericin B (3, 5, 6, 8), miconazole and ketoconazole (6, 8), but not always to 5-fluorocytosine (4, 6, 8). Studies of susceptibility of the organisms to fluconazole have not been reported. As in other kinds of fungal endocarditis, the treatment of Trichosporon endocarditis requires valvular replacement because relapses are usual in spite of prolonged antifungal therapy (13). It should be emphasized that our patient survived for four years, probably because of the two prothesis replacements and the intensive antifungal therapy given. However, we could not eradicate the fungus and the patient suffered many complications. This case, as well as the other cases reported, suggest that Trichosporon endocarditis cannot be Completely cured with current therapy. Our patient received fluconazole for one month, but in a late stage of the disease. Recently, Isalska and Stanbridge (14) described a patient with prosthetic valve endocarditis due to Candida parapsilosis who had negative blood cultures for one year while on fluconazole therapy and did not undergo valve replacement. Although this experience is very limited and susceptibility tests were not carried out, long-term prophylactic therapy with this new triazole agent may be of some advantage in fungal infections.
References 1. Benne! JE: Miscellaneous fungi. In: Mandell GL, Douglas RG, Bennett JE (ed): Principles and practice of infectious diseases. John Wiley, New York, 1990, p. 2031-2034. 2. Waish T J, Newman KR, Marcia Moody MS, Wharlon RC, Wade JC: Trichosporinosis in patients with neoplastic disease. Medicine 1986, 65: 268-279.
Eur. J. Clin. Microbiol. Infect. Dis.
3. Marier R, Zakhireh B, Downs J, Wynne B, Hammond GL, Andriole VT: Trichosporon cutaneum endoearditis. ScandinavianJournal of Infectious Diseases 1978, 10: 255-256.
4. Arnold AG, Gribbin B, De Leval M, Mseartney F, Slack M: Trichosporon capitatum causing recurrent fungal endocarditis. Thorax 1981, 36: 478--480. 5. Brahn E, Leonard PA: Trichosporon cutaneum endocarditis: a sequela of intravenous drug abuse. American Journal of Clinical Pathology 1982, 78: 792794.
6. Thomas D, Mogahed A, Leclere JP, Grosgogeat Y: Prosthetic valve'endocarditis caused by Trichosporon cutaneum. International Journal of Cardiology 1984, 5: 83-87.
7. Reyes CV, Stanley MM, Rippon FW: Trichosporon beigelii endocarditis as a complication of peritoneovenous shunt. Human Pathology 1985, 16: 857-859. 8. Reinhart HH, Urbanski DM, Harrington SD, Sobel JD: Prosthetic valve cndocarditis caused by Tr&hosporon beigelii. American Journal of Medicine 1988, 84: 355-358. 9. Madhavan T, Eisses J, Quino EL: Infections due to Trichosporon cuta~reum, an uncommon systemic pathogen. Henry Ford Hospital Medical Journal 1976, 24: 27-30.
10. Winston D J, Balsley GE, Rhodes J, Linn6 SR: Disseminated Trichosporon capitanon infection in an im11. 12.
13.
14.
mmosuppressed host. Archives of Internal Medicine 1977, 137: 1192-1195. Manzella JP, Berman J, Kukrika MD: Trichosporon beigelii fungemia and cutaneous dissemination. Archives of Dermatology 1982, 118: 343-345. Haupt HM, Merz WC, Bemhorner WE, Vaughn WP, Saral R: Colonization and infection with Trichosporon species in the immunocompromised host. Journal of Infectious Diseases 1983, 147: 199-203. Scheld WM, Sande MA: Endocarditis and intravascular infections. In: Mandell GL, Douglas RG, Bennett JE (ed): Principles and practice of infectious diseases. John Wiley, New York, 1990, p. 670-706. Isalska B J, Stanbridge TN: Fluconazole in the treatment of Candidal prosthetic valve endocarditis. British Medical Journal 1988, 297: 178-179.
3. Venditti M, Posteraro B, Morace G, Marlino P: In vitro comparative activity of flueonazole and other antifungal agents against Blastoschizomyces capitatus. Journal of Chemotherapy 1991, 3: 13-15. 4. Surmont I, Vergauwen B, Marcelis L, Verbist L, Ver. hoef G, Boogaerls M"First report of chronic meningitis caused by Trichosporon beigelii. European Journal of Clinical Microbiology and Infectious Diseases 1990, 9: 226-229. 5. Arndt CAS, Walsh TJ, McCully CL, Balis FM, Pizzo PA, Poplack DG: Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. Journal of Infectious Diseases 1988, 157: 178-180. 6. Sugar AM, Saunders C: Oral fluconazole suppressive therapy of disseminated cryptococcosisin patients with acquired immunodeficiency syndrome. American Journal of Medicine 1988, 85: 481--489. 7. Maksymiuk AW, Thongprasert S, Hopfer R, Luna M, Fainstein V, Bodey GP-"Systemic eandidiasis in cancer patients. American Journal of Medicine 1984, 77, Supplement 4D: 20-27.
Long-Term Survival of a Patient with Prosthetic Valve Endocarditis due to Trichosporon beigelii J. M a r t i n e z - L a c a s a 1, J. Mafia 1., R. Niub61, G. R u f i 2, A. Saez 3, E Fern~indez-Nogu6s I
A case is described of a 49-year-old man with rheumatic aortic valve disease who developed endocarditis seven years after valvular replacement. Trichosporon beigelii was isolated from the blood, a peripheral thrombus, and the removed prothesis. After two valve prosthesis replacements and prolonged antifungal therapy, the patient survived for four years, but eventually died as a consequence of multiple septic complications due to the same organism. To the authors' knowledge, this is the longest survival time of any reported case of Trichosporon prosthetic valve endocarditis.
Trichosporon beigelii is a yeast that is known as the causative agent of white piedra, a fungal infection of the hair shaft (1).It was traditionally con1Department of Internal Medicine, 2Infectious Diseases Unit, and 3Department of Pathology, Hospital de Bellvitge "Prfnceps D'Espanya", Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
Eur. J. Clin. Microbiol. Infect. Dis.
sidered to be a non-invasive fungus, but in recent years several cases of fungemia and systemic infection in immunocompromised patients have been described (2). As far as we know, only six well documented and two possible cases of Trichosporon beigelii and Trichosporon capitaturn endocarditis have been previously reported in the literature (3-10). We describe a case of Trichosporon beigelii endocarditis in a patient who survived several years and developed multiple septic complications. Case Report. In January 1985, a 49-year-old man was admitted to our hospital because of fever. Seven years earlier a Carpentier-Edwards valve prothesis had been inserted due to double aortic lesion of rheumatic origin. Three weeks before admission he had had fever and pain in the left upper abdominal quadrant. On physical examination the patient appeared acutely ill and febrile, with an aortic regurgitation murmur and hepatosplenomegaly. The erythrocyte sedimentation rate was 52 mm, hemoglobin 11.4 g/100 ml, white blood cell count 12500/mm 3 with 2 1 % eosinophils, alkaline phosphatase 163 1U, and gamma globulin 22 g/l. An echocardiogram disclosed aortic prosthetic valve vegetations and a 99mTc sulfur colloid liver-spleen scan was normal. Blood samples were obtained for culture and empiric treatment with penicillin and streptomycin was started. However, the fever persisted and ten days after admission the patient complained of leg pain and his right leg was cold, with absence of popliteal and pedal pulses. A popliteal thrombus showing the presence of hyphae was removed surgically. Trichosporon beigelii grew in three blood cultures and the thrombus. Amphotericin B was given and the prothesis was replaced. Trichosporon beigelii was also isolated from the prosthetic valve vegetations. In vitro susceptibility tests showed the organism to be sensitive to amphotericin B (MIC 0.3 mcg/ml), and ketoconazole (MIC 4 mcg/ml), and resistant to 5-fluorocytosine (MIC 20 mcg/ml). After the operation the patient developed severe hepatic cholestasis and a liver biopsy demonstrated granulomatous hepatitis. Repeat blood cultures were negative and a complete course of 2.5 g of amphotericin B was administered for eight weeks. The patient improved and was discharged. In October 1985 he was readmitted because of fever and peripheral embolisms in the fingers and toes. Blood cultures were again negative and an echocardiogram did not show vegetations. The patient improved without any additional treatment. In March 1986 fever and the
Vol. 10, 1991
peripheral vascular disturbances reappeared. Trichosporon beigelii was again isolated in two blood cultures and a new prothesis replacement was carried out. The prosthetic valve culture was sterile, and a pacemaker was inserted due to atrioventricular block. A course of 2.5 g of amphotericin B was again administered followed by 400 mg oral ketoconazole per day. In March 1987, while he was receiving ketoconazole, fever and peripheral embolisms recurred; blood cultures were negative and an echocardiogram disclosed no vegetations. The eosinophil count was 1,080/ ram3. Ketoconazole was discontinued after ten months and the patient improved spontaneously. In May 1988 he complained of lumbar pain for several weeks. An x-ray of the lumbar spine, a vertebral technetium scan, and a CT scan of the lumbar spine showed osteolysis of the 3rd and 4th lumbar vertebrae; a needle aspiration was sterile. Bed rest and analgesic therapy were prescribed. Two months later, fever and peripheral embolisms in the toes reappeared. Three days after admission the patient had headache and decreased consciousness. A CT scan of the brain showed parietal hemorrhage and an arteriography disclosed multiple cerebral aneurysms. Surgery was performed with drainage of the hematoma and resection of several mycotic aneurysms; cultures were sterile. A new replacement of the aortic prothesis was considered too hazardous, and treatment with 2.5 g of amPbotericin B was readministered for the third time with a good clinical result. In April 1989 the patient complained of abdominal pain, vomiting and new peripheral vascular disturbances. Arteriography showed the presence of an embolus in the upper mesenteric artery. Oral fluconazole therapy (400 mg per day) was administered with some improvement. No tests of susceptibility to fluconazole could be carried out. One month later, while he was receiving flUconazole, Tr&hosporon beigelii was isolated in two blood cultures. The patient died a few days later with shock and fever. Post mortem examination disclosed an aortic prothesis with large Vegetations, and mukiple embolisms ~nd infarcts m the kidneys and brain. Trichosporon beigelii was isolated from both the prothesis and the kidney. Discussion. Trichosporon beigelii, also referred to as Trichosporon cutaneum, belongs to the family CryPtococcaceae. It is the etiologic agent of white piedra, an infection of the hair shafts. It is ocCasionally encountered among the normal flora of
757
Figure 1: Large vegetationson the prosthetic aortic valve.
Figure 2: Mcthenamine-silver stain of prosthetic valve vegetation showing branching mycelia[ elements (magnit'ication x 500). the skin, and also has been isolated from respiratory secretions, urine and stool of healthy persons (1). It is traditionally considered a nonpathogenic fungus. However, in the past 25 years several cases of disseminated infection in immunocompromised patients have been described (2). So far, however, only six well documented cases (3-8) and two possible cases (9, 10) of Tricho~poron endocarditis have been reported in the literature. Although neutropenia probably predisposes to disseminated infection in immunocompromised patients (2), most cases of endocarditis have been reported in patients with prosthetic valves (3, 4, 6, 8) or native valve involvement associated with parenteral drug addiction or peritoneovenous shunt (5, 7). The portal of entry of the organism is uncertain. The gastrointestinal tract, upper respiratory tract and endovascular catheter contamination have
758
often been implicated (10-12). In prosthetic valve endocarditis, previous surgery may play an important role due to possible skin colonization by Trichosporon beigelii in immunocompetent patients. Trichosporinosis may be difficult to diagnose because blood cultures may be repeatedly negative. Cultures of the prothesis or the endovascular material most often reveal the presence of Trichosporon (3-8).
Trichosporon spp. causing endocarditis have usually been sensitive to amphotericin B (3, 5, 6, 8), miconazole and ketoconazole (6, 8), but not always to 5-fluorocytosine (4, 6, 8). Studies of susceptibility of the organisms to fluconazole have not been reported. As in other kinds of fungal endocarditis, the treatment of Trichosporon endocarditis requires valvular replacement because relapses are usual in spite of prolonged antifungal therapy (13). It should be emphasized that our patient survived for four years, probably because of the two prothesis replacements and the intensive antifungal therapy given. However, we could not eradicate the fungus and the patient suffered many complications. This case, as well as the other cases reported, suggest that Trichosporon endocarditis cannot be Completely cured with current therapy. Our patient received fluconazole for one month, but in a late stage of the disease. Recently, Isalska and Stanbridge (14) described a patient with prosthetic valve endocarditis due to Candida parapsilosis who had negative blood cultures for one year while on fluconazole therapy and did not undergo valve replacement. Although this experience is very limited and susceptibility tests were not carried out, long-term prophylactic therapy with this new triazole agent may be of some advantage in fungal infections.
References 1. Benne! JE: Miscellaneous fungi. In: Mandell GL, Douglas RG, Bennett JE (ed): Principles and practice of infectious diseases. John Wiley, New York, 1990, p. 2031-2034. 2. Waish T J, Newman KR, Marcia Moody MS, Wharlon RC, Wade JC: Trichosporinosis in patients with neoplastic disease. Medicine 1986, 65: 268-279.
Eur. J. Clin. Microbiol. Infect. Dis.
3. Marier R, Zakhireh B, Downs J, Wynne B, Hammond GL, Andriole VT: Trichosporon cutaneum endoearditis. ScandinavianJournal of Infectious Diseases 1978, 10: 255-256.
4. Arnold AG, Gribbin B, De Leval M, Mseartney F, Slack M: Trichosporon capitatum causing recurrent fungal endocarditis. Thorax 1981, 36: 478--480. 5. Brahn E, Leonard PA: Trichosporon cutaneum endocarditis: a sequela of intravenous drug abuse. American Journal of Clinical Pathology 1982, 78: 792794.
6. Thomas D, Mogahed A, Leclere JP, Grosgogeat Y: Prosthetic valve'endocarditis caused by Trichosporon cutaneum. International Journal of Cardiology 1984, 5: 83-87.
7. Reyes CV, Stanley MM, Rippon FW: Trichosporon beigelii endocarditis as a complication of peritoneovenous shunt. Human Pathology 1985, 16: 857-859. 8. Reinhart HH, Urbanski DM, Harrington SD, Sobel JD: Prosthetic valve cndocarditis caused by Tr&hosporon beigelii. American Journal of Medicine 1988, 84: 355-358. 9. Madhavan T, Eisses J, Quino EL: Infections due to Trichosporon cuta~reum, an uncommon systemic pathogen. Henry Ford Hospital Medical Journal 1976, 24: 27-30.
10. Winston D J, Balsley GE, Rhodes J, Linn6 SR: Disseminated Trichosporon capitanon infection in an im11. 12.
13.
14.
mmosuppressed host. Archives of Internal Medicine 1977, 137: 1192-1195. Manzella JP, Berman J, Kukrika MD: Trichosporon beigelii fungemia and cutaneous dissemination. Archives of Dermatology 1982, 118: 343-345. Haupt HM, Merz WC, Bemhorner WE, Vaughn WP, Saral R: Colonization and infection with Trichosporon species in the immunocompromised host. Journal of Infectious Diseases 1983, 147: 199-203. Scheld WM, Sande MA: Endocarditis and intravascular infections. In: Mandell GL, Douglas RG, Bennett JE (ed): Principles and practice of infectious diseases. John Wiley, New York, 1990, p. 670-706. Isalska B J, Stanbridge TN: Fluconazole in the treatment of Candidal prosthetic valve endocarditis. British Medical Journal 1988, 297: 178-179.
