A Case of Polymycotic Septicemia Caused by Trichosporon Beigelii
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Jpn. J. Med. Mycol. Vol. 29, 120-126, 1988 ISSN 0583-0516 A Case of Polymycotic Septicemia Caused by Trichosporon beigelii, Candida albi cans and Candida krusei Takeshi Mori, Tomoo Kohara, Makiko Matsumura, Takao Hirano, Yoshihisa Wakabayashi, Hideo Ikemoto, Akiko Watanabe*, Wako Yumura**, Yoshiro Sakamoto**, Toshikazu Shirai** and Hikaru Kume*** Department of Internal Medicine *Central Laboratory for Medical Sciences, Division of Pathology **Department of Pathology, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113, Japan ***Department of Pathology, Kitasato University, 1-15-1, Kitasato, Sagamihara, Kanagawa, 228, Japan [Received for Publication: December 15, 1987] This report describes a patient with acute leukemia complicated with polymycotic septicemia caused by Candida albicans, C. krusei and Trichosporon beigelii (cutaneum). Oral flucytosine and intravenous miconazole were administered, but the patient died on the 59th hospital day. At autopsy, T. beigelii and C. albicans were isolated from the liver, and T. beigelii was isolated from the lung by cultural examination and pathological investigation by the peroxidase/anti-peroxidase solution method. The patient was intubated with an intravenous catheter for hyperalimentation for a long time. The indwelling intravenous catheter appeared to be the major factor leading to the f ungemia. T. beigelii (cutaneum), a so-called "nonpathogenic yeast," must be considered a potential cause of fungemia. Key words: polymycotic septicemia, Candida albicans, Candida krusei, Trichosporon beigelii (cutaneum), peroxidase/antiperoxidase solution method Introduction Case Report Advances in chemotherapy have contributed to An 18-year-old male the prolongation of life of patients with malignant He complained of lower abdominal pain in early diseases, but they have conversely led to an September, 1985, but this subsided after medica- increased incidence of opportunistic infections, tion administered by a local physician. However, especially fungal infections. in late September he again experienced lower We experienced a patient with acute leukemia abdominal pain with a cough, sputum, pharyngeal complicated with polymycotic septicemia caused pain and a fever of 37--38C and revisited the by Candida albicans, Candida krusei and same doctor. He was diagnosed as having acute Trichosporon beigelii (cutaneum). These fungi are myeloblastic leukemia, because the WBC count members of Cryptococcaceae. These fungal el- was 11,000/mm3 (Myeloblast 80.5, Band. 1, Seg.1, ements had a similar appearance in histological Eosino. 0.5, and Lymph. 17%) (Auer body was sections, but were differentiated from each other positive). He was admitted to our hospital on by the peroxidase/anti-peroxidase solution October 10, 1985. method. Cases of polymycotic septicemia seem to At admission, the body temperature was 37.4C, be rare. and there was slight anemia but no apparent lymphadenopathy, hepatosplenomegaly, edema or Jpn. J. Med. Mycol. Vol. 29 (No. 2), 1988 121 Table 1. Fungi and bacteria isolated from the patient *: detected in the tip of the indwelling catheter B: cultured from blood +: slight growth S: cultured from sputum 2+: moderate growth F: cultured from feces 3+: strong growth purpura. From the time of admission, cefotaxime, aclarubicin, 6-mercaptopurine and prednisolone, tobramycin, polymyxin B and flucytosine (2400 the myeloblasts were not diminished. The patient mg/day) were administered for prophylaxis, and was thus treated with high-dose cytosine ara- he was treated with combination chemotherapy binosite, because the leukemia was resistant to consisting of vindesine, prednisolone, 1-aspar- the therapy. aginase and daunorubicin. The number of leuko- Blood, sputum, feces and urine were frequently cytes decreased to 100/mm3, but the myeloblasts examined, and C. albicans, C. krusei and T. beigelii increased to 94% on the 5th day after the end of were detected from the blood, as shown in Table 1. the combination chemotherapy. Therefore, he was Urine culture was always negative. On December treated again with combination chemotherapy of 12, chest X-rays showed infiltration of the enocitabine, aclarubicin, 6-mercaptopurine and bilateral total lung fields, especially the bilateral prednisolone from November 10. However, at the middle lung fields, and the dose of miconazole was same time, a high fever of 39-40C persisted. increased from 1200mg to 1800mg/day; still a Pseudomonas cepacia was transiently detected in high fever persisted. On December 18, miconazole the venous blood. Cefotaxime was replaced, in was changed to intravenous amphotericin B. turn, with cefmenoxime, ceftizoxime and ce- However, the patient's condition deteriorated, and fotiam, but the fever did not abate. On December he died on December 19, 1985 (59th hospital day). 2, chest X-rays showed a little infiltration in the Intravenous hyperalimentation had been con- right middle lung field. Because the various anti- tinued from the patient's admission through biotics had been ineffective and infiltration ap- death, except for November 11 to December 6. peared on the chest X-ray, a fungal infection was Laboratory tests showed disturbances of the suspected; flucytosine was therefore changed to liver and renal functions; GOT increased from 66 intravenous miconazole (1200mg/day). Even after IU/l on December 9 to 365IU/l on December 16, the combination chemotherapy of enocitabine, GPT increased from 62IU/l on December 9 to 252 122 真菌 誌 第29巻 第2号 昭和63年 IU/1 on December 16, BUN increased from 21 mg/dl on December 12 to 74mg/ml on December 19 and serum creatinine increased from 0.8mg/ml on December 12 to 2.7mg/ml on December 19. Microscopic hematuria was detected on December 18. A Candida hemagglutination test on the patient's serum was negative (1:80-160; positive titer is 1:>320). The minimal inhibitory concentrations (MICs) of amphotericin B, miconazole and flucytosine for the isolate C. albicans, C. krusei and T. beigelii were determined by the agar dilution technique1). The MICs of amphotericin B, miconazole and flucytosine for C. albicans were 1.56, 6.25 and 0.78 ag/ml, while they were 3.13, 3.13 and 12.5ug/ml for C. krusei, and 6.25, 3.13 and over 100ug/ml for Fig. 1. Fungal elements in the liver by scanning T. beigelii. electron microscopy. Autopsy Findings The bone marrow was found to be filled with myeloblastic leukemic cells, but there was no evidence of infiltration of leukemic cells into the other organs. The characteristic findings were extensive mycoses in the liver, lungs, kidneys, spleen, and also microscopic fungal lesions in the adrenal glands, pancreas and myocardium. T. beigelii was cultured from the liver and the lung, while C. albicans was cultured only from lung tissues obtained at autopsy. Scanning electron microscopy showed the mor- phologic fungal elements to be of various sizes (Fig. 1) and developed from cracks in the tissue and through Kohn's pores in the lung (Fig. 2). However, the fungal elements of Candida spp. Fig. 2. Electron microscopic fungal elements in could not be distinguished from those of T. the lung, developing through Kohn's pores or beigelii. cracks in the tissue. For the purpose of differentiation of the fungal elements, the same specimens of the liver and 3). The same specimens in Fig. 3 was stained by lung used for culture studies were also investi- the PAP method using anti-C. albicans rabbit gated by the peroxidase/anti-peroxidase solution serum (Fig. 4) and also stained by the PAP method method (PAP method) using anti-T. beigelii and using anti-T. beigelii rabbit serum (Fig. 5). Thus, anti-C. albicans rabbit sera. In the liver, the fungal the fungal elements of C. albicans and T. beigelii elements were stained violet by PAS staining (Fig. were differentiated from each other by the PAP Jpn. J. Med. Mycol. Vol. 29 (No. 2), 1988 123 method and found to be in very close proximity. But, in the lung tissue, only fungal elements of T. beigelii were detected. Discusion In severely immunocompromised patients, systemic fungal infections may often occur, and they can be fatal. The most frequent causative fungi are Candida and Aspergillus species. Sys- temic candidiasis occurs in about 10 percent of patients with acute leukemia, 1 percent of pa- tients with malignant lymphoma and 0.5 percent Fig. 3. Fungal elements in the liver by PAS staining. (original magnification X100). of patients with solid tumors2). The incidence of fungemia caused by Candida species has increased each year3). Predisposing factors to systemic fungal infec- tions are neutropenia caused by administered anticancer drugs, gastrointestinal ulceration due to increased use of broad-spectrum antibacterial agents (which has been associated with increases in both the frequency and degree of colonization of the gastrointestinal tract by fungi), and indwelling catheters which are used in cancer patients to facilitate the administration of medication4). Candida species are a part of the normal flora of the human body. Trichosporon is a normal in- Fig. 4. Same microscopic field as in Fig. 3. Candidal pseudohyphae stained with peroxidase/ habitant of the soil and is considered to be a anti-peroxidase solution method using anti-C. noninvasive fungus, but it occasionally appears in albicans rabbit serum. (original magnification the normal flora of the human body. Therefore, X100). when Trichsporon is detected in clinical speci- mens, an infection by Trichosporon is often over- looked or belatedly diagnosed, and its major clinical presentation is a superficial infection of the hair shaft known as white piedra. Only rarely has T. beigelii been reported as the cause of deep- tissue infections or disseminated diseases. Candidal pneumonia due to aspiration of in- fected secretion is an infrequent infection, and it is usually secondary to hematogenous dis- semination. T. beigelii, similar to Candida species, rarely causes primary pulmonary infections. In this Fig. 5. Same microscopic field as in Figs. 3 and 4. Fungal elements of T. beigelii stained by PAP patient, we couldnot conclude that the infection method using anti-T.