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Non ..Sporulating : An Opportunistic Fungallnfedion in a Neutropenic Patient

GG Gan, MRCP', A Kamarulzaman, FRACP*, KY Goh, MRCP', KP Ng, PhD", SL Na, MLT**, TS Soo-Hoo, PhD'*, *Department of Medicine, "Department of , Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur

fungal organism, non-sporulating Chrysosporiu1n in a neutropenic patient following an Systemic fungal infections are a major cause of induction for relapsed acute morbidity and mortality in neutropenic patients. lymphoblastic leukemia. We were unable to Approximately 25% of patients with leukemia determine the exact genus of Chlysosporium have evidence of fungal infection at autopsy. The species. To our knowledge, with the clinical incidence of fungal infection is increasing in findings and the significant blood cultures, this is immunosuppressed patients especially in the the first reported case in Malaysia. hcmato-oncology patients. This is probably due to several factors including prolonged period of , the use of broad spectrum antibacterial therapy, the increasing use of central Case Report venous access devices, and disruption of the A 50 year old female with a prior history of acute normal mucosal barrier in patients post­ lymphoblastic leukemia in rClllission was chemotherapy. Common fungi isolated fr01ll this admitted to the hospital for lobar pneumonia. group of patients are , , She was on oral maintenance chemotherapy Penicillium marneffei and JIIlucor. Increasingly, consisting of daily lnercaptopurine and weekly infections with that were not previously methotrexate started about a year ago. The recognised as pathogenic are being described. We induction chemotherapy used to treat .the acute present a case of systemic infection of a rare leukemia 2 years previously was of the BFM

This article was accepted: 15 January 2002 Corresponding Author: GG Gan, Department of Medicine, Faculty of Medicine, University Malaya, 50603 Kuala Lumpur

] 18 Mod J Malaysia Val 57 No ] Mar 2002 NON-SPORULATING CHRYSOSPORIUM: AN OPPORTUNISTIC FUNGAL INFECTION

protocol which consisted of clauDorubicin, , vincristine and L-asparaginase. She developed Citrobacter as well as Escherichia coli bacteriuria post-chemotherapy. Other complication from the induction chemotherapy was drug induced mellitus which recovered after chemotherapy was completed.

The patient presented with one week duration of productive cough. On physical eXa11unation at admission, she was febrile with a temperature of 38°C, and crepitations were audible over her right lung. A chest X-ray revealed a lobar opacity in the right lower lung field. The initial lahoratory findings revealed Hb of 5.4g/dl, WCC of 1.4 x 10'/L (neutrophils 66% with no blast seen) and platelet of 105,000. The blood sugar level was elevated C19.0mmoIlL) and insulin therapy was commenced. Her oral maintenance chemotherapy was stopped. Intravenous antibacterial therapy Fig. 1: CT scan of brain showing the c014<;isting of ampicillin/sulbactam 1.2g three times subdural collection. a day and aZithromycin 500mg daily were commenced. The was later changed to cefepime at a dosage of 2g twice daily. There was present on admission. A repeated blood (Bactec no growth from 2 different sets of blood cultures. 9240, Becton Dickinson) and sputum cultures The settled after 3 days of and were taken on the same clay. Repeat chest x- ray there was symptomatic improvement. Treatment showed persistent right lower lung opacity. A with cefepime was continued for a total of 10 days. bronchoscopy was performed the next day. The skins lesions were biopsied and broad spectrum As her blood count did not improve, a bone antibiotic therapy, including imipenem, marrow examination was perfonned which vancomycin and (J mg/kg/day) showed a relapse of acute lymphoblastic were instituted. A CT scan of thorax and abdomen leukemia (blast count of 78%). Induction showed collapse consolidation in the apical chemotherapy comprising of idarubicin and segment of the right lower lung. CT scan of the cytosine arabinoside was started. She remained brain and paranasal sinuses showed bilateral quite well and afebrile despite becoming maxillary sinusitis and an irregular hypodense neutropenic on the 8th day following area extending from the vertex down to the chemotherapy (+8). Subcutaneous granulocyte temporal region which was reported as possibility colony stimulating factor (G-CSI') was started. due to a fungal or a resolving subdural hematoma (Fig. 1). The patient clid not exhibit On the 10th day post-induction chemotherapy any neurological signs. (+10), she became febrile and complained of feeling of increasingly unwell with difficulty in After 48 hours, a was isolated from the breathing. On examination, there was blood cultures drawn on day +10. The isolate was hepatomegaly, bilateral axillmy skin lesions and subcultured onto SDA and incubated at 37"C. On left nasal ulceration, These were not previously day 4, a flucose, white colony with a lobulated

Med J Malaysia Val 57 No I Mar 2002 119 CASE REPORT

centre appeared. The reverse siele of the colony The patient improved and became afebrile alter was also whitish in color. Microscopic 15 days of antibacterial and therapy. examination of the colony on day 7 using tease The antibacterial therapy was stopped but mount technique with a drop of lactophenol amphotericin B was continued. Her skin and cotton blue, thin segmented and irregularly nasal lesion resolved and she was discharged on branched hyphae were seen. There was no day +51 with thrice weekly intravenous production of conidia. A subculture from SDA amphotericin B Clmg/kg/day) and oral was made onto blood agar and incubated at 37°C ittaconazole 400mg daily. for evidence of sporulation. A slide culture was also made using Potato Dextrose agar and A repeat bone marrow examination 2 weeks after incubated at 37°C, the slide culture was examined discharge showed that the patient did not achieve periodically at low power (lOx) objective until remission even though her blood counts had day 10. The coverslip was then removed and improved. Her diabetes is now controlled with stained with lactophenol cotton blue (Fig. 2). The oral hypoglycemic agents. The patient remained fine stI:ucture of this fungus consisted of well and afebrile. After discussion with her family, segmented hyphae with no conidia formation. a decision was ITh'1de to withhold any fUlther The original SDA after 2 weeks of incubation at chemotherapy in view of possible persistent 37°C and the subculture on blood failed fungal infection. A repeat CT of brain anel thorax to show evidence of sporulation after prolonged 2 months after the initial CT scan showed the incubation. The fungus isolated from blood was previous subdural collection has resolved and the therefore identified as non-sporulating consolidation of the right lung has decreased in Chrysosp01'ium based on the whitish texture of size. She is still receiving the intravenous the coiony, branching hyphae and absent of amphotericin B three times a week as an conidia production. outpatient basis,

Bronchoalveolar lavage did not grow any Discussion organism. The skin showed local ulceration and and stained negative Opportunistic fungal infections typically occur in for any fungal elements or acid fast bacilli, immunocompromised patients. Disseminated unfortunately, the biopsy specimen was not and are the most submitted for fungal culture. common fungal infections in neutropenic

Fig. 2: Macroscopic and microscopic structure of non­ sporulating Chrysosporium.

120 Med J Malaysia Val 57 No 1 Mar 2002 NON-SPORULATING CHRYSOSPORIUM: AN OPPORTUNISTIC FUNGAL INFECTION

patients. All are considered y.biquitous in nature. lesion recovered with the treatment. The blood These patients have extremely poor outcome culture which grew the organism was unlikely and often the poor survival is attributed to a to be due to contamination in view of her delay in diagnosis. clinical finclings and significant improvement of the symptoms after commencement of Members of the genus ChJYSOS!JOrium that are amphotericin B. human include Chrysosporium paruum, and C. paruum var. creserL.,. The fungi There are only a few reports on extrapulmonalY are common soil saprophytes. The colonies are disease in humans caused by chlysosporium. predominantly white to tan, varied from waxy to Stillwell et. al. ' found chrysosporiwn parvum as a powdery. The reverse is mostly colorless to tan. cause of osteomyelitis in a 24 year old man. They The conidiophores are not easily differentiated treated the patient with amphotericin B with from irregularly branched hyphae. The members complete resolution of the clisease. In produced aleurioconidia terminally, at the end of immunocompromised patients, Warwick et. at. 2 short or long lateral 2 or 3 conidia. The fungus described an invasive chlysmporium infection of isnlated from blood is filamentous, grew rapidly the paranasal sinuses extending into the central on SDA producing a white fluffy mycelium with a nervous system in a young girl following bone lobulated centre within 4 days. The colonial marrow transplantation. She subsequently clied morphology and microscopic structure are very from the infection. Roilides ct. al.' described a 15 similar to species of members of genus year old boy with chronic granulomatous disease Chrysosporiuln. However, as the fungus failed to who had disseminated chlysosporiwn infections sporulate after prolonged incubation of SDA or causing pneulnonia and osteomyelitis of the tibia. growing on Potato Dextrose Agar incubated at The disease recurred when amphotericin B was 37"C for 14 days, the isolate was called a non­ stopped despite on oral maintenance of oral sporulating G1Jrysosporium. . The disease finally resolved after a year of liposomal amphotericin B. In human, there are only rare reports of deep infection caused by Chlysosporium species, and In summary, we reported a case of disseminated most of which are difficult to treat. The first infection caused by non-sporulating confirmed case of human chlysosporial infection, Chrysmporium in a patient with acute or adiaspir01nycosis was reported in 1964. lymphoblastic leukemia. The treatment of this Adiaspiromycosis is usually confined to the lung disseminated infection is unknown, however, the because inhaled conidia do not replicate or combination of amphotericin B and oral disseminate. Both solitalY and diffuse forms of itraconazole appeared to be effective in pubnonalY disease have been described. controlling the infection. Like GlJlysosporiwn However, in our patient, the adiaconidia may infection, this fungus may cause an aggressive have form endospores or changed to mycelia as and disseminated disease and may be fatal her own defenses were destroyed, the mold could especially in an immunocompromised patient. have spread hematogenously throughout her The prolonged therapy with amphotericin B may body. The source of her infection may have be the standard of care. Although the Colony­ originated from the lung. stimulating factors, for examples, the granulocyte, granulocyte-macrophage colony stimulating Her persistent fever was treated empirically with factors may have a favourable effect on the broad spectrum antibacterial therapy and incidence and outcome of this group of patients, amphotericin B. The skin lesions and the nasal further study is needed.

Med J Malaysia Val 57 Na 1 Mar 2002 121 CASE REPORT

1. Stillwell W. Chlysosporium, a new causative agent 3. Roilides E, Sigler L, Bibashi E, Katsifa H, Flaris N, in osteomyelitis. A case report. Clin Orthop 1984; Panteliaclis C. Disseminated infection due to 184, 190-92. CI:nysosporium zonatwn in a patient with chronic granulomatous disease and review of non­ 2. Warwick A, Ferrieri P, Burke 13, Blazar 13R. Aspergillus fungal infections in patients with this Presumptive invasive Chrysosporium infection in a disease. J Microb 1999; 37(1), 18-25. bone marrow transplant recipient. Bone Marrow Transplantation 1991; 8: 319 -22.

122 Med J Malaysia Val 57 No 1 Mar 2002