Support Care Cancer (1996) 4:291-293 © Springer-Verlag 1996

Miguel A. Sanz Francisca L6pez Maria L. Martlnez Guillermo F. Sanz Jesfis A. Martinez Guillermo Martin Miguel Gobernado

M.A. Sanz, M.D. (Y~) • F. L6pez, M.D. G.F. Sanz, M.D. • J.A. Martfnez, M.D. G. Martfn, M.D. Haematology Service, La Fe University Hospital, Avenida Campanar 19, E-46009 Valencia, Spain TeL/Fax: (34) 6-386 87 57 e-mail: [email protected] M.L. Martfnez, M.D. • M. Gobernado, M.D. Microbiology Service, La Fe University Hospital, Avenida Campanar 19, E-46009 Valencia, Spain

Disseminated Blastoschizomyces capitatus infection in acute myeloblastic leukaemia Report of three cases

Abstract T h r e e new cases of Blastoschizomyces capitatus infection occurring in neutropenic patients with acute myeloblastic leukaemia are reported. B. capitatus was isolated f r o m blood cultures in all patients. All three patients were treated with amphotericin B, but only one was cured f r o m the infection. O u r study confirms the emergence of B. capitatus as an opportunistic agent of disseminated fungal infection in leukaemic patients.

Introduction T h e emergence of previously considered harmless yeast fungi as significant h u m a n pathogens is increasing, particularly in i m m u n o c o m p r o m i s e d patients [3]. Fungi of the genus Trichosporon are one of these newly recognized agents that result in invasive fungal infections [12]. Trichosporon capitatum (now properly Blastoschizomyces capitatus) has b e e n recognized as a causal agent in a few cases of invasive fungal infection. Until recent years, 11 cases of B. capitatus infection had b e e n r e p o r t e d [1, 2, 4, 6, 7, 9-11, 13, 14], and only 4 of t h e m were in patients with acute leukaemia [2, 7, 11]. In 1990, Martino et al. [8] r e p o r t e d 12 additional cases observed over a period of 6 years in a single institution. In order to contribute to a better knowledge of the infection caused by B. capitatus in leukaemic patients, we here report 3 new cases that occurred in patients with acute myeloblastic leukaemia. Along with other known risk factors for invasive fungal infection, such as intensive chemotherapy, previous antibiotherapy and deep and persistent neutropenia, each of our patients had a H i c k m a n catheter.

Key words Fungal infection • A c u t e leukaemia • Immunocompromised •

Blastoschizornyces capitatus

Case reports All patients were admitted to the leukemia unit of La Fe University Hospital, Valencia (Spain) for the treatment of acute leukaemia. No oral antibiotic prophylaxis was employed except a non-absorbable antifungal solution of amphotericin B. Specimens for mycological examination were seeded on Sabouraud's glucose and Littman Oxgall media (Difco Laboratories, USA) and both were incubated at room temperature and 37 °C for 14 days. Yeast isolates were identified with the AutoMicrobic system (Vitek Systems Inc., Hazelwood, Mo.).

Case 1 A 63-year-old woman with acute myeloblastic leukaemia in complete remission was readmitted for intensification chemotherapy with daunorubicin and high-dose cytarabine. A Hickman catheter had been placed before remission induction and maintained for 6 months of postremission therapy. Four days after starting intensification chemotherapy, she became extremely neutropenic (< 100 polymorphonuclear neurophils/ixl) and febrile. Empirical therapy with ceftazidime plus amikacin was started. After 9 days, while fever remained, she developed lethargy and disorientation, and empirical amphotericin B (0.71 mg kg -~ day -1) was added to the regimen. B. capitatus was isolated from blood and cerebrospinal fluid cultures (one of each). NevertheIess, she died 2 days lat-

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er in septic shock when only a total dose of 120 mg amphotericin B had been administered. Permission for autopsy was denied.

Case 2 A 25-year-old woman was admitted for treatment of acute promyelocytic leukaemia with daunorubicin 2 mg kg 1 day 1 for 5 days. She had previously developed fever in the context of severe neutropenia, and a combination of imipenem plus amikacin was started. Streptococcus sp. and Staphylococcus aureus bacteraemia were documented. The patient remained without fever for 3 days, but with the appearance simultaneously of abdominal pain and water diarrhoea she became febrile again. Empirically, metronidazole was unsuccessfully tried over 3 days and then amphotericin B (1.3 mg kg ~ day 1) was begun. B. capitatus had been isolated from stool 3 days before the start of amphotericin B and also from one blood culture 1 day after. Finally, amphotericin B was stopped after achieving a total dose of 1660 mg and 16 days without fever. At present, the patient remains cured of the infection and the leukaemia is in remission.

Case 3 A 31-year-old woman with acute myeloblastic leukaemia in complete remission, with a Hickman catheter inserted before remission induction was started, was readmitted to receive consolidation with daunorubicin 60 mg m -2 day -~ for 3 days plus cytarabine 200 mg m -2 day 1 as a continuous intravenous infusion for 7 days. Neutropenic fever was successfully treated empirically with ceftazidime plus amikacin. Fever reappeared 10 days later and amphotericin B was added at a dose of 0.5 mg kg -1 day -1 on the first day, increasing to 1.16 mg kg -1 day -~ on the following days. B. capitatus was isolated from four blood cultures. A continuous febrile status led to removal of the Hickman catheter. B. capitatus was also isolated from the catheter's tip. Thereafter, the lack of improvement and the appearance of a generalized maculo-papular rash prompted us to exchange amphotericin B for ketoconazole (800 mg/day). Although the patient became afebrile, she developed cholestasis and bilateral pulmonary infiltrates. Sputum samples and urine cultures repeatedly showed growth of B. capitatus in spite of antifungal therapy. Nine days later, while remaining without fever, she developed a bacteraemic infection (Corynebacterium sp. and Enterococcus faecalis) and died. Unfortunately, postmortem examination was not authorized.

Discussion The current use of m o r e aggressive approaches in the t r e a t m e n t of cancer patients has resulted in an increasing n u m b e r of patients who develop invasive fungal infections. Although Aspergillus, Candida and Mucor are the most frequent isolates, others, previously considered as non-pathogenic fungi, are emerging as causative agents of potentially fatal invasive infections. This is the case with B. capitatus, a fungus normally considered

a minor c o m p o n e n t of normal skin flora. Since the first reported B. capitatus infection in 1977 [13], in a patient with aplastic anaemia who underwent bone m a r r o w transplantation, until recently only 5 other cases had occurred in severely i m m u n o c o m p r o m i s e d patients with haematological malignancies, 4 with acute leuk a e m i a [2, 7, 11], and 1 multiple m y e l o m a [6]. H o w e v er, in 1990 Martino et al. [8] reported 12 additional cases that had been observed over a period of 6 years in a single institution. This would seem to confirm B. capitatus as an emerging cause of invasive fungal infection in leukaemia patients. W e hereby report 3 new cases of infection caused by B. capitatus that occurred in adult patients with acute myeloblastic leukaemia. Like most reported cases of systemic B. capitatus infection, our patients had several known risk factors for developing invasive fungal infection: heavy t r e a t m e n t with chemotherapy, previous administration of broad-spectrum antibiotics, a central venous catheter ( H i c k m a n catheter), and long and severe neutropenia. Soil is the normal habitat of B. capitatus and it is rarely isolated from the environment in hospitals. Nevertheless, it is occasionally isolated f r o m the skin and mouths of patients in w h o m it is merely a commensal. T h e lungs, alimentary tract, and central venous catheters are known potential ports of entry for these fungi. Once the fungus is in the circulatory system, it rapidly leads to systemic infection, as has been d e m o n s t r a t e d experimentally in normal rabbits [5]. The entry of fungi into colonized patients is easier when there is disruption of the mechanical barriers, and it is very c o m m o n in patients receiving cytotoxic treatment (mucositis, intravenous catheters, etc.). Obviously the immunosuppression of these patients, particularly neutropenia, contributes enormously to the severity and mortality of these fungal infections. It is r e m a r k a b l e that Martino et al. [8] reported no data referring to the n u m b e r of patients who had intravenous catheters, particularly when it is a well-known risk factor of fungal infection. Before the three survivors of the series reported by Martino et al. [8], only the patient reported by Oelz et al. [11] had a favourable clinical o u t c o m e a m o n g leukaemic patients with B. capitatus infection. All 4 of these patients were successfully treated with a m p h o t e r icin B plus 5-flucytosine, while the one survivor in our series (case 2) was treated with amphotericin B alone. Our study confirms the emergence of B. capitatus as an opportunistic agent of disseminated fungal infection in leukaemic patients.

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