Refractory Candidal Meningitis in an Immunocompromised Patient Cured by Caspofungin

Abstract

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...

Central nervous system infections in immunocompromised patients – update on diagnostics and therapy

“…In the case of amphotericin B refractoriness or incompatibility, a combination therapy comprising fluconazole and FC might be used [12]. Case reports also showed efficacy of novel antifungal drugs, such as caspofungin in the treatment of Candida meningitis [37]. However, it has to be mentioned that caspofungin penetrates poorly into the CNS, at least if the blood-brain barrier is intact [31].…”

“…In patients with Candida meningitis, CSF analysis frequently reveals pleocytosis with a mean count of *600 cells/ mL. Despite the diagnostic obstacles, there are several methods for improving the success of CSF isolation, such as culturing a large CSF volume (a minimum of 5 mL), analysis of ventricular CSF, CSF centrifugation or the use of submicron filters and inoculating CSF into enriched liquid medium [37]. Following these methods, yeasts can be detected in CSF in about 40% by direct microscopy and in up to 80% by fungal cultures.…”

Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014

“…• Continue therapy until at least 4 weeks after resolution of radiological signs and neurological symptoms 72,73 • Remove intraventricular devices 71,72 • There are limited data on posaconazole, voriconazole or echinocandins for CNS candidiasis [74][75][76][77] Ocular candidiasis AmB-D 0.7-1 mg/kg, daily plus 5-fluorouracil 25 mg/kg, 6-hourly 62,72 or fluconazole 400-800 mg, daily (6-12 mg/kg) L-AMB 3-5 mg/kg, daily or voriconazole 6 mg/kg, 12-hourly for two doses then 3-4 mg/kg, 12-hourly [78][79][80] • Treat for 4-6 weeks and until ocular lesions have resolved 72,81 • Consider intravitreal antifungal therapy or surgical vitrectomy in the presence of vitritis • Echinocandins are not recommended due to concerns regarding their ocular penetration 81 Candida osteomyelitis…”

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

“…As the first of the echinocandins to be approved for the treatment of IC, caspofungin has been used extensively for the treatment of all forms of serious candidal infections over the past 4 years (87,114,134,171,261). Thus far, clinical experience with caspofungin and IC has been good (41,87,114,163,171).…”