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nonfatal trichoderma citrinoviride pneumonia in an acute myeloid leukemia patient


Ann Hematol (2008) 87:501–502 DOI 10.1007/s00277-007-0427-y

LETTER TO THE EDITOR

Nonfatal Trichoderma citrinoviride pneumonia in an acute myeloid leukemia patient
Rita Kviliute & Algimantas Paskevicius & Jolanta Gulbinovic & Rokas Stulpinas & Laimonas Griskevicius

Received: 23 November 2007 / Accepted: 3 December 2007 / Published online: 8 January 2008 # Springer-Verlag 2007

Dear Editor, We report a 49-year-old woman with acute myeloid leukemia (AML) with inv (16) (p13q22), who underwent a high-dose cytarabine consolidation. On day+17 after the end of chemotherapy, the patient developed neutropenic fever (absolute neutrophil count (ANC)—0.001×109/l). A chest X-ray showed bilateral pulmonary infiltrates. Meropenem and vancomycin were administered. On day+25 the patient became afebrile and the ANC recovered to 1.3× 109/l. A chest computed tomography (CT) scan performed on day+27 was consistent with fungal pulmonary infection
R. Kviliute (*) : R. Stulpinas : L. Griskevicius Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Santariskiu 2, Vilnius LT-08661, Lithuania e-mail: rita.kviliute@santa.lt A. Paskevicius Institute of Botany, Zaliuju ezeru 49, Vilnius LT-08406, Lithuania A. Paskevicius Centre of Laboratory Diagnostics, Vilnius University Hospital Santariskiu Clinics, Santariskiu 2, Vilnius LT-08661, Lithuania J. Gulbinovic Department of Drug Safety, Medical Product Agency, Dag Hammarskj?lds v?g 42, Uppsala SE-751 03, Sweden L. Griskevicius Clinics of Internal, Family Medicine and Oncology, Vilnius University Hospital Santariskiu Clinics, Santariskiu 2, Vilnius LT-08661, Lithuania

showing bilateral infiltration, cavitation in the S9 segment of the right lung with intracavitary nodule and ground-glass opacity surrounding the lesion (Fig. 1a). Fibrobronchoscopy (FBS) revealed tumor-like mass obstructing S3 bronchus of the right lung. Pathological examination of the mass showed fungal mycelium in necrotized bronchial tissues (Fig. 2). Microbiological examination of bronchoalveolar lavage identified filamentous fungus Trichoderma citrinoviride. The amphotericin B, ketoconazole and itraconazole minimal inhibitory concentrations (MICs) were all >32 μg/ml. Post hoc MICs for voriconazole and caspofungin were 4 μg/ml and 0.125 μg/ml respectively (as determined on archived T. citrinoviride isolate). Despite high MIC, amphotericin B treatment was started and continued for 21 days to the total dose of 1450 mg. The patient remained in good clinical condition with no clinical signs of pulmonary infection, low CRP (18 mg/l), normal ANC (4.08×109/l) and was discharged for outpatient follow-up without any antifungal therapy despite remaining pulmonary infiltration on chest X-ray. Two and a half months later, chest CT scan showed resolved fungal infection (Fig. 1b). Eventually, the patient underwent allogeneic matched unrelated donor stem cell transplantation and currently remains in complete hematological and molecular remission with no signs of pulmonary infection at 7 months of observation. No signs and symptoms of fungal infection were observed after stem cell transplantation. Trichoderma genus is known to take part in the decomposition of plant residues in the soil [1]. It is also listed among the causes of rare opportunistic fungal infections in human. Six species of the genus Trichoderma (T. harzianum, T. koningii, T. longibrachiatum, T. pseudokoningii, T. viride and T. citrinoviride) have been identified as etiologic agents of infection in immunocompromised

502 Fig. 1 a Chest CT scan showing cavitation in the S9 segment of the right lung with intracavitary nodule and groundglass opacity surrounding the lesion. b Repeated chest CT scan 2.5 months later showing resolved fungal infection

Ann Hematol (2008) 87:501–502

patients [1]. Trichoderma has been associated with 22 cases of reported human infections. Five documented cases have been observed in oncohaematological patients: pulmonary infection in an AML patient, which was successfully treated with amphotericin B, voriconazole and caspofungin [2]; disseminated infection in an AML patient after bone marrow transplantation (BMT), who died despite treatment with amphotericin B and 5-flourocytosine [3]; disseminated infection in an acute lymphoblastic leukemia patient after BMT, who died despite treatment with amphotericin B and itraconazole [4]; brain and ethmoidal abscess in an acute leukemia patient successfully treated by surgery, amphotericin B and itraconazole [5] and disseminated infection in a lymphoma patient who died despite treatment with amphotericin B and itraconazole [6]. Other reports of Trichoderma infections include eight cases of peritonitis in patients with continued ambulatory peritoneal dialysis, four cases in solid organ transplant recipients, one case in a patient after aorta surgery, one case of keratitis (not specified) and skin infection in a pediatric patient with aplastic anemia [2]. Trichoderma was also detected in cerebrospinal fluid of an AIDS patient [7]. In total, ten patients out of 22 with Trichoderma infection have died in spite of various antifungal treatments.

The major problem with Trichoderma genus is its poor susceptibility to antifungal drugs. Most isolates proved to be resistant to fluconazole and 5-fluorocytosine. Some were reported to be susceptible or intermediately susceptible to amphotericin B, itraconazole, ketoconazole and myconazole. However, resistance to amphotericin B and high MIC levels of itraconazole and ketoconazole have also been reported [1]. To our knowledge, this is the first published case report of Trichoderma citrinoviride infection in a human. There was no radiological improvement despite amphotericin B therapy. However, there was a gradual and complete resolution of pulmonary infiltration on CT after ANC recovery, paving the way for the uneventful allogeneic stem cell transplantation.

References
1. Kredics L, Antal Z, Doczi I, Manczinger L, Kevei F, Nagy E (2003) Clinical importance of the genus Trichoderma. A review. Acta Microbiol Immunol Hung 50:105–117 2. De Miguel D, Gomez P, Gonzalez R, Garcia-Suarez J, Cuadros JA, Banas MH, Romanyk J, Burgaleta C (2005) Nonfatal pulmonary Trichoderma viride infection in an adult patient with acute myeloid leukemia: report of one case and review of the literature. Diagn Microbiol Infect Dis 53:33–37 3. Gautheret A, Dromer F, Bourhis JH, Andremont A (1995) Trichoderma pseudokoningii as a cause of fatal infection in a bone marrow transplant recipient. Clin Infect Dis 20:1063–1064 4. Richter S, Cormican MG, Pfaller MA, Lee CK, Gingrich R, Rinaldi MG, Sutton DA (1999) Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: species identification and review of the literature. J Clin Microbiol 37:1154–1160 5. Seguin P, Degeilh B, Grulois I, Gacouin A, Maugendre S, Dufour T, Dupont B, Camus C (1995) Successful treatment of a brain abscess due to Trichoderma longibrachiatum after surgical resection. Eur J Clin Microbiol Infect Dis 14:445–448 6. Myoken Y, Sugata T, Fujita Y, Asaoku H, Fujihara M, Mikami Y (2002) Fatal necrotizing stomatitis due to Trichoderma longibrachiatum in a neutropenic patient with malignant lymphoma: a case report. Int J Oral Maxillofac Surg 31:688–691 7. Amato JG, Amato VS, Amato Neto V, Heins-Vaccari EM (2002) An AIDS patient with Trichoderma. Rev Soc Bras Med Trop 35:269

Fig. 2 Fungal mycelium (Gordon-Sweet staining ×200)


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