A Disseminated Infection with the Antifungal-Multiresistant Teleomorphic Fungus Neocosmospora Vasinfecta in a Patient with Acute B-Lymphoblastic Leukemia
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Medical Mycology Case Reports 2 (2013) 44–47 Contents lists available at ScienceDirect Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr A disseminated infection with the antifungal-multiresistant teleomorphic fungus Neocosmospora vasinfecta in a patient with acute B-lymphoblastic leukemia Fre´de´ric Gabriel a,b,c, Mahussi D’Almeida a,b,c, Olivier Albert a,b,c, Vale´rie Fitton-Ouhabi a,b, Thierry Noel¨ a,b, Isabelle Accoceberry a,b,c,n a Universite´ de Bordeaux, Microbiologie Fondamentale et Pathoge´nicite´ UMR 5234, F-33000 Bordeaux, France b CNRS, Microbiologie Fondamentale et Pathoge´nicite´, UMR 5234, F-33000 Bordeaux, France c Centre Hospitalier Universitaire de Bordeaux, Laboratoire de Parasitologie-Mycologie, F-33000 Bordeaux, France article info abstract Article history: We report on a fatal invasive infection due to the ascomycetous fungus Neocosmospora vasinfecta,ina Received 21 December 2012 20-year-old European patient suffering from an acute lymphoblastic leukemia. The infection could not Accepted 8 January 2013 be controlled by a bitherapy combining liposomal amphotericin B and voriconazole. This is the second case of disseminated infection reported with this unusual fungus, which develops under its tele- Keywords: omorphic state, is fully resistant to all systemic antifungals, and which is known to live in tropical Neocosmospora vasinfecta countries. Teleomorph & 2013 International Society for Human and Animal Mycology. Published by Elsevier B.V All rights Antifungal-resistance reserved. Invasive fungal infection 1. Introduction t [4,11] translocation and blasts negative for CD20 and CD10. The patient was treated according to the GRAALL 2005 protocol Neocosmospora vasinfecta is a filamentous ascomycete belong- NCT00327678 (Group for Research in Adult Acute Lymphoblastic ing to the order Hypocreales known to be a plant pathogen Leukemia). Complete remission was achieved in October 2008, responsible for root- and fruit-rot, and seedling damping off in a but the scheduled allogenic stem cell transplantation (HSCT) large variety of plants [1,2]. It is a common soil-borne fungus could not be performed because no compatible donor had been normally isolated in (sub)tropical areas, which is now considered identified. Intensification therapy was started, and the good by certain authors as a possible new emerging pathogen for condition of the patient allowed him back to work part-time in humans, in spite of a very low incidence in human pathology so May 2009, and full-time in September 2009. far [2,3]. The cases reported included a leg granuloma in a renal On December 2009, a subsequent medullar relapse was diag- transplant recipient [3], a posttraumatic osteoarthritis [1] and a nosed along with a H1N1 influenza pneumonia. The patient was corneal ulcer in immunocompetent patients [4],andafatal treated with L-asparaginase encapsulated within erythrocytes disseminated infection in a patient with acute nonlymphocytic (GRASPAs), according to the GRASPALL-protocol 2005-01 [6]. leukemia [5]. We report here a case of fatal systemic N. vasinfecta Bone marrow examination showed persistence of 490% blast infection in a patient with an acute B-lymphoblastic leukemia. This cells. After a second-line rescue therapy, the patient received in is the fifth case of human infection reported with this unusual March 2010 an allogenic stem cell transplant (Australian cord fungal species and the second case of disseminated infection. blood with two mismatches on class I, 2.7 Â 107 total nucleated cells/kg and 0.12 Â 106 CD34þ cells/kg). On Day 0 (D0) of HSCT, two peri-umbilical papules of 10–15 mm 2. Case diameter, painful, slightly erythematous but not pruriginous were noted. Histopathological examination of a papule biopsy revealed A 20-year-old man, native of France, was diagnosed in August branched, hyaline, septate hyphae invading the reticular dermis 2008 with a B-cell acute lymphoblastic leukemia carrying the and the dermo-hypodermic junction. Intravenous bitherapy com- bining liposomal amphotericin B (3 mg/kg/j) and voriconazole (600 mg/kg/day for the first 48 h, then 400 mg/kg/day) was imme- n Corresponding author at: Universite´ de Bordeaux, Microbiologie Fondamentale et diately started. On D1, computed tomography showed one macro- Pathoge´nicite´ UMR 5234, F-33000 Bordeaux, France. Tel.: þ33557574844; fax: þ33557574803. nodule (3 cm diameter) in the right upper lobe of lung, and no E-mail address: [email protected] (I. Accoceberry). sinus abnormalities. 2211-7539/$ - see front matter & 2013 International Society for Human and Animal Mycology. Published by Elsevier B.V All rights reserved. http://dx.doi.org/10.1016/j.mmcr.2013.01.004 F. Gabriel et al. / Medical Mycology Case Reports 2 (2013) 44–47 45 Serum galactomannan (GM) assay (Platelia& Aspergillus Ag Kit, was performed by E-test (BioMe´rieux) on RPMI medium and revealed Bio-Rad), performed twice a week, was positive on D3 multiresistance. The MIC values were: amphotericin B432 mg/ml, (index¼0.53). On D4, a high GM assay index (5.8) was measured voriconazole 24 mg/ml at 24 h then 432 mg/ml at 48 h, posaconazole on a bronchoalveolar lavage (BAL), whereas no Aspergillus grew 432 mg/ml, and caspofungin 432 mg/ml. from the BAL culture. Blood cultures were performed daily from D0. Two blood cultures inoculated on D7 and D8 yielded fungi, respectively after 3 days of growth on fungal media (Mycosis 3. Discussion Bactec, Becton-Dickinson, United States), and 8 days of growth on aerobic media. It is noteworthy that, over the period from D0 to The genus Neocosmospora belongs to the Nectriaceae family D10, 33 other aerobic and anaerobic flasks, and one Mycosis flask, and contains several species mainly pathogenic for plants [2]. remained negative. Their occurrence in human pathology is rare. However, the The patient received lenograstim, but remained in aplasia. In species N. vasinfecta has been reported to cause a broad spectrum spite of the antifungal bitherapy, and of a voriconazole blood of infections, including superficial infections such as corneal ulcer concentration of 7 mg/ml, the infection continued to disseminate [4], locally invasive infections, such as leg granuloma and rapidly. Other skin lesions appeared on abdomen, legs and skull. osteoarthritis [1,3], and one disseminated infection [5]. The Myocardial injury was suspected from a T wave inversion in right clinical aspects and the severity of Neocosmospora infections precordial leads (V1–V4) along with troponin and myoglobin largely depend on the immune status of the patients [9]. Neocos- increased levels. The patient finally died at D12. mospora is a pathogen that can develop in the immunocompetent The culture of skin biopsy yielded a mold that grew rapidly within patient [1], through a direct traumatic inoculation. Some profes- two days on Sabouraud-glucose-agar medium containing chloram- sional activities can be considered as a risk factor, like farming phenicol and cycloheximide at 25 1C and on Sabouraud-glucose-agar and gardening, as reported for the farmers growing groundnuts medium containing chloramphenicol without cycloheximide at 30 1C, and cotton in India [4]. In the present clinical case, the patient forming white lanate colonies (Fig. 1). Microscopic examination of with an acute B-lymphoblastic leukemia was severely immuno- slide cultures showed septate hyaline hyphae, simple conidiophores, compromised and though very susceptible to infectious diseases. phialides, and fusoı¨d or ellipsoidal microconidia, sometimes two- However, the isolation of N. vasinfecta was intriguing. The fungus septate. Phialides were either cylindrical or aciculate, solitary or is known to live in the soil of tropical areas and in the preceding produced as a component of a complex branching system. Discrimi- clinical cases, the patients were originating from, or had traveled nation between Fusarium and Acremonium genus was difficult with recently in, Africa [1,3,5], or South-India [4]. In the present case, such a microscopic morphology. After 8 days of incubation, orange to the patient originated from the southwest of France, and no copper-colored fruiting bodies developed. The fruiting bodies were journey in a tropical country was documented. The critical identified as perithecial ascomata and contained monoseriate ascus question is how the patient was infected by the fungus. Microbial with 8 ascospores inside. Mature ascospores were globose to ellip- sampling in the close environment of the patient at the hospital soı¨dal and possessed a rough ornamented thick wall. did not reveal the presence of N. vasinfecta. The patient was pastry Molecular identification was performed by PCR amplification apprentice. One possibility is that he could have been in contact and nucleotide sequencing of the internal transcribed sequence with the fungus while manipulating flours or plant and fruit (ITS) of the ribosomal RNA genes, a segment of the 18S rDNA products used in pastry, collected or manufactured in tropical gene, and a part of the Ef1-a translation elongation factor (TEF1) countries and imported in Europe. As for plants, animals, virus gene, as previously described [7]. Ribosomal ITS regions were and other microorganisms, this poses the question of the circula- amplified using the universal primer pair ITS1 (50-TCCGTAGGT- tion of normally endemic potential pathogenic fungus around the GAACCTGCGG-30) and ITS4 (50-TCCTCCGCTTATTGATATGC-30). world through human activities. Region of the 18S rDNA gene was amplified