Fatal Fungemia with Scedosporium Prolificans in a Patient with Acute Myeloid Leukemia
Total Page：16
File Type：pdf, Size：1020Kb
Med. Mycol. J. Med. Mycol. J. Vol. 55（No. 4）, 2014 E 63 Vol. 55E, E 63 − E 70, 2014 ISSN 2185 − 6486 Case Report Fatal Fungemia with Scedosporium prolificans in a Patient with Acute Myeloid Leukemia Makoto Nishimoriઃ, Toshio Takahashi, Eiko Suzuki, Taiichi Kodakaઃ, Nobuhiro Hiramotoઃ, Kiminari Itohઃ, Hiroko Tsunemineઃ, Kyoko Yaritaઅ, Katsuhiko Kameiઅ, Hiroshi Takegawaઆ, Takayuki Takahashiઃ ઃDepartments of Hematology Shinko Hospital, Kobe Laboratory Medicine, Shinko Hospital, Kobe અMedical Mycology Research Center, Chiba University, Chiba આLaboratory Medicine, Kobe City Medical Center General Hospital, Kobe ABSTRACT Scedosporium prolificans（S. prolificans）is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia（AML-M5a）with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected. Key words：Scedosporium prolificans, acute myeloid leukemia, β-D-glucan, mold sinuses, or through direct inoculation, such as in Introduction skin puncture 4）. S. prolificans-affected body regions include the blood, lungs, bones, and soft Scedosporium species（spp.）are ubiquitous tissue, and S. prolificans disseminates to multiple fungi, distributed in living environments such as organs in many cases. Although rare, S. prolifi- polluted water and soil, and classified as ascomy- cans infection often causes fatal disease; dissemi- cota in a group of molds 1）. Scedosporium spp. nated disease is particularly associated with a consist of 2 species: Scedosporium prolificans（S. high mortality rate of 87.5% 5）, because active proloficans）and S. apiospermum. S. prolificans antifungal agents against S. prolificans are cur- was first revealed to be pathogenic in 1984, rently not available. Here, we report a patient with although the incidence of infection is very low, acute myeloid leukemia（AML）who developed with 1.33 affected cases per 100,000 people in the fatal fungemia with S. prolificans during induction United States 1,2）. S. prolificans mostly affects chemotherapy for AML. immunocompromised people, such as patients with hematologic diseases 3）. Human infection Case report often results from the inhalation of spores present in the environment into the lungs or paranasal A 71-year-old woman with leukopenia was Address for correspondence : Takayuki Takahashi Department of Hematology, Shinko Hospital Received : 30, December 2013, Accepted : 19, August 2014 [email protected] E 64 Medical Mycology Journal Volume 55, Number 4, 2014 Table 1．Laboratory findings on admission Hematology Chemistry WBC 1.8×109/L TP 7.1 g/dL Neu 46.8% Alb 4.2 g/dL Eos 0.0% LDH 232 IU/L Bas 0.8% AST 26 IU/L Mon 1.6% ALT 43 IU/L Lym 47.0% ALP 191 IU/L Blast 2.8% T-bil 0.9 mg/dL RBC 3,250×109/L BUN 10.5mg/dL Hb 11.3 g/dL Cre 0.6 mg/dL Ht 32.6% UA 4.5mg/dL Plt 153×109/L Na 143 mEq/L Reti 1.0% K 4.2 mEq/L Coagulation Cl 109 mEq/L Fib 304 mg/dL PT 106% Bone marrow aPTT 32.3 sec Ncc 2.2×104/mL D-dimer 0.4μg/mL Megakaryocytes Decreased Serology M/E ratio 4.55 CRP 0.3 mg/dL Blasts 31.3% MMP-3 63.5ng/mL POX （＋） IgA 293 mg/dL ASD （−） IgG 1,141 mg/dL α-NB （+） IgM 66 mg/dL Karyotype 46, XX MMP-3: matrix metalloproteinase-3（normally 17.3 to 59.7 ng/dL）; POX: peroxidase staining; ASD: naphthol AS-D chloroacetate esterase staining; α-NB: α-naphthyl butyrate esterase staining. admitted to our hospital because of suspected （normally 870 to 1,700 mg）, and IgM of 66 mg/dL AML. Three years before admission, she had been （normally 46 to 260 mg）, suggesting well-control- diagnosed with rheumatoid arthritis（RA）and led RA and intact humoral immunity. A bone Sjögren>s syndrome. Two years before admission, marrow aspirate showed hypocellularity with a she had been treated with tocilizumab（8 mg/kg, nucleated cell count of 21.1×109/L, in which blast weekly）for the acute exacerbation of RA, with cells comprised 31.1%. Some of these blast cells improvement of the disease. Two months before showed differentiation toward immature mono- admission, she had developed leukopenia（white cytes（Fig. 1A）and were positive for peroxidase cell count: 1.8×109/L）. Therefore, tocilizumab was and α-naphthyl butyrate esterase staining（Fig. discontinued with persistent leukopenia, and a 1B, 1C）. A diagnosis of AML-M5a according to the bone marrow aspirate led to suspected AML. FAB classification was made. Thus, she was referred to our hospital. She had a history of tocilizumab therapy, and Physical and physiological examinations on was thereby suggested to be in an immunocom- admission were unremarkable. Laboratory find- promised state. We, therefore, employed CAG ings on admission are shown in Table 1. The white chemotherapy（low-dose cytarabine, acralubicin, blood cell（WBC）count was 1.8×109/L, with 2.8% and filgrastim）as remission induction therapy for blast cells, 46.8% neutrophils, 1.6% monocytes, AML. The clinical course of the patient is shown in and 47.0% lymphocytes, a hemoglobin concentra- Fig. 2. On day 7 after the initiation of CAG therapy, tion of 11.3 g/dL, and platelet count of 153×109/L. she developed anal pain due to an exacerbated Serological tests revealed C-reactive protein hemorrhoid with fever above 38℃. The hemor- （CRP）of 0.3 mg/dL（normally below 0.3 mg）, rhoid was swollen, reddish, and partially erosive matrix metalloproteinase-3（MMP-3）of63.5ng/dL and hemorrhagic. The WBC count was 0.5×109/L （normally 17.3 to 59.7 ng/dL）, IgA of 293 mg/dL wih 0% neutrophils. We administered tazobac- （normally 110 to 410 mg）, IgG of 1,141 mg/dL tam/piperacillin for the infectious hemorrhoid, Med. Mycol. J. Vol. 55（No. 4）, 2014 E 65 Fig. 1．Smear preparation of a bone marrow aspirate on admission to our hospital. A: Many immature monocytes can be seen. A small number of these abnormal cells show monocytic matura- tion（arrow）（Wright-Giemsa staining, ×1,000）. These leukemic cells are positive for peroxidase staining（B） and α-naphthyl butyrate esterase staining（C）. which brought about transient resolution of the susceptible to vancomycin, while the culture of fever. On day 8, we discontinued the CAG viscous fluid taken by swabbing from the erosive because of agranulocytosis and a clearly infec- portion of the painful hemorrhoid yielded a tious portion of the painful hemorrhoid. On day 11, negative result. On day 13, however, she became she again became febrile with a body temperature more febrile and developed frequent diarrhea of 38℃ or higher; therefore, we added vancomycin with abdominal tenderness in addition to the anal for possible infection caused by methicillin-resis- pain. We, therefore, added micafungin for possible tant Staphylococcus aureus. On day 12, blood intestinal candidiasis presumably derived from culture yielded Enterococcus faecium which was the infectious hemorrhoid. On day 14, she had a E 66 Medical Mycology Journal Volume 55, Number 4, 2014 Anal pain Fever Peritoneal irritaon CAG WBC Neut (/μL) 5,000 －80 (%) －70 4,000 －60 －50 3,000 －40 2,000 WBC －30 －20 1,000 Neut 䘩 －10 CRP 40 (mg/dL) 30 20 10 5 10 15 17 TAZ/PIPC VCM MCFG MEPM L-AMB Fig. 2． Clinical course of the present patient. CAG: cytarabine, acralubicin, and filgrastim; Neut: neutrophils; TAZ/PIPC: tazobactam/piperacillin; VCM: vancomycin; MCFG: micafungin; MEPM: meropenem; L-AMB: liposomal-amphotericin B. persistently high fever with peritoneal irritation ing of the pathogens from the blood culture is sign, and a laboratory test showed that the serum shown in Fig 3A. Morphologically, the fungus had concentration of β-D-glucan had elevated to 525 mold-like features, although we could not identify pg/mL（normally below 11 pg/mL）. From this the exact fungal species at that time. The growth time-point, she became drowsy, with a progres- pattern of the fungus in BD difco Potato Dextrose sive deterioration of consciousness. Although we Agar（Nippon Becton Dickinson Co., Ltd., Tokyo, subsequently obtained negative results from Japan）isshown in Fig. 3B. The color of the fungus repeated blood cultures, we changed micafungin colony was blackish to light brown, and it was to liposomal amphotericin B and tazobactam/ covered with whitish filamentous organisms. On piperacillin to meropenem for possible infections cellophane tape preparation, Scedosporium spp. by micafungin-resistant fungi or multiple-drug-re- was suspected because of the characteristic sistant bacteria, without improvement of her feature of the hyphae（Fig. 3C）. A few weeks later, condition. She developed multiple organ failure this fungus was identified as S. prolificans by and died on day 17. Autopsy was not performed. rRNA sequence analysis 6）, performed at the The day after her death, we received a report that Medical Mycology Research Center, Chiba Uni- a fungus had been grown from blood culture with versity, Chiba, Japan. An in vitro susceptibility a culture bottle（BACTEC Aerobic Plus, but not test 7） of the isolated S. prolificans, performed at BACTEC Anaerobic Plus; Nippon Becton Dickin- the Department of Laboratory Medicine, Kobe son Co., Ltd., Tokyo, Japan）, which was per- City Medical Center General Hospital, Kobe, formed on day 13.