Reactions 1243 - 14 Mar 2009

WHO ADR database contained one report of aspergillosis(MedDRA) associated with carmustine.★ SAntineoplastics/corticosteroids

Aspergillus terreus infection (first report withcarmustine): case report

A 60-year-old woman developed pulmonary and cerebralAspergillus terreus infection after carmustine polifeprosan20 wafer implantation (Gliadel) and treatment withtemozolomide and chronic corticosteroids [dosages anddurations of therapies to reaction onset not stated].

The woman underwent gross total resection withcarmustine polifeprosan 20 wafer implantation, externalbeam radiotherapy and two cycles of temozolomidechemotherapy, for left temporal lobe glioblastoma. Herclinical course was complicated by deep vein thrombosiswith pulmonary embolisms, allergic reactions to phenytoinand valproic acid, heparin-induced thrombocytopenia andlong-term corticosteroid requirement [specific drugs andindication not clearly stated] with subsequent cushingoidfeatures. Grade-3 leucopenia and neutropenia were alsonoted following the first cycle of temozolomide. Tumourprogression was noted 5 months after initial diagnosis,prompting an additional temozolomide cycle. During aroutine follow-up, the patient’s family reported a 2–3 weekhistory of functional decline. She was nonambulatory,confused, excessively sleepy during the day and hadnocturnal visual and auditory hallucinations. Herneurological examination was limited, she demonstratedlack of antigravity strength in the proximal lowerextremities and responded to questions and followedcommands inconsistently. She had a BP of 154/101 and anarea of cellulitis associated with a firm, tender, nodular areain the right axilla. Her serum glucose was 453 mg/dL andshe had mildly elevated lactate dehydrogenase and totalbilirubin. Hypoventilation and a questionable retrocardiacnodular opacity were evident during chest radiograph. CTscan reveled multifocal parenchymal opacities, someconsolidated and some nodular in appearance. Urineculture was positive for Candida albicans. CSF had a WBCcount of 7 [no units stated] with 99% neutrophils, a RBCcount of 1 [no units stated], a glucose level of 99 mg/dL anda protein level of 65 mg/dL. Two new hypodense lesionswere observed upon head CT. Brain MRI characterisedthese lesions as faintly enhancing with focal haemorrhage.Subsequent excisional brain biopsy, revealed extensivenecrosis with the more intact fragments showing intenseneutrophilic response, vascular thrombosis and necrosis.In the abscess, extensive tissue haemorrhage wasobserved. Septal fungi forming 45° angle branching wereobserved. Cultures from the brain lesion and subsequentbronchoalveolar lavage grew Aspergillus terreus. Bronchiallavage cultures also grew Candida albicans.

The woman received amphotericin B lipid complex andfluconazole; however clinical decline persisted andsymptomatic brain oedema increased. Hospice care waspursued and she died 6 days after the diagnosis wasestablished; no postmortem examination was performed.

Author comment: "In our patient, chronic steroid use inthe setting of concurrent chemotherapy appeared to havebeen the major risk factor. . . Our patient did have apersistently low absolute lymphocyte count for most of hertreatment course, attributed to both the provision of high-dose steroids and the specific chemotherapy agent,temozolomide".Damek DM, et al. Aspergillus terreus brain abscess mimicking tumor progressionin a patient with treated glioblastoma multiforme. Clinical Neuropathology 27:400-407, No. 6, Nov-Dec 2008 - USA 801132182

» Editorial comment: A search of AdisBase, Medline andEmbase did not reveal any previous case reports ofAspergillus terreus infection associated with carmustine. The

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Reactions 14 Mar 2009 No. 12430114-9954/10/1243-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved