Candidal meningitis is a rare infectious disease that usually leads to substantial morbidity and mortality. We present a case of candidal meningitis refractory to systemic antifungal therapy (amphotericin B and fluconazole). A 63-year-old female with lymphoblastic lymphoma and myelodysplasia with leukemia transformation developed prolonged fever and headache on the seventh day following intrathecal prophylactic chemotherapy. A lumbar puncture showed neutrophilic pleocytosis, and a cerebrospinal fluid culture yielded Candida albicans. The clinical course was complicated by brain edema, subarachnoid hemorrhage, and hydrocephalus. Parenteral therapy with amphotericin B alone or amphotericin B in combination with fluconazole or intrathecal administration of amphotericin B failed to eradicate C. albicans in the cerebrospinal fluid. After 7 days of caspofungin therapy, however, the cerebrospinal fluid became sterile and the patient gradually regained consciousness. She was discharged 1 month after completing 4 weeks of caspofungin therapy. There were two critical issues we thought to be relevant to the favorable outcome of this case. First, isolation of C. albicans was achieved by inoculating enriched liquid medium with cerebrospinal fluid. Second, there is a potential therapeutic benefit of caspofungin in treating a fungal infection of the central nervous system. CASE REPORTA 63-year-old woman had lymphoblastic lymphoma and myelodysplasia with leukemia transformation, initially presenting as a neck mass, anemia, and thrombocytopenia. She received the first course of chemotherapy, consisting of a hyperCVAD regimen (cyclophosphamide, vincristine, epirubicin, and dexamethasone), on 23 December 2002 and the second course of chemotherapy on 14 February 2003 (day 1). The latter treatment included intrathecal methotrexate (day 2) and intrathecal cytosine arabinoside (day 8). Neutropenic fever developed 8 days after initiation of chemotherapy, accompanied by progressive headache and vomiting. The fever did not subside under parenteral treatment with vancomycin and meropenem. A lumbar puncture was therefore done on day 23, and study of the cerebrospinal fluid (CSF) revealed neutrophilic pleocytosis (white blood cell count, 1,500/mm 3 ; 87% neutrophils). The patient's consciousness deteriorated following the lumbar puncture, a phenomenon thought to be related to a subarachnoid hemorrhage and brain edema (Fig. 1A). The patient was treated for bacterial meningitis on the basis of the initial CSF data. An Omaya reservoir was inserted on day 27 because of hydrocephalus. CSF drawn from the Omaya reservoir on day 33 yielded Candida albicans. Amphotericin B (1 mg/kg of body weight per day) was given for central nervous system (CNS) candidiasis, starting on day 39. Brain magnetic resonance imaging (MRI) scans on day 41 showed hydrocephalus and hematoma over the premedullary space, which was thought to be the result of a rupture of a mycotic aneurysm (Fig. 1B). However, after 29 days of amphotericin B therapy, with a cumulative dose of...
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