Ja. Perez et al., FLUCONAZOLE THERAPY IN COCCIDIOIDAL MENINGITIS MAINTAINED WITH INTRATHECAL AMPHOTERICIN-B, Archives of internal medicine, 155(15), 1995, pp. 1665-1668
Background: Meningitis follows approximately 0.15% to 0.75% of cases o
f extrapulmonary coccidioidomycosis. Successful treatment of coccidioi
dal meningitis (CM) has generally required intrathecal therapy with am
photericin B, which often causes significant toxic effects and discomf
ort to the patient. Prior to fluconazole, azoles had not been efficaci
ous in CM either because of toxicity at elevated doses or because of p
oor cerebrospinal fluid distribution. Fluconazole however, has been fo
und to have both good cerebrospinal fluid penetration and a favorable
side effect profile, Methods: We studied 11 patients with CM who were
maintained with amphotericin B and were then switched to oral fluconaz
ole therapy alone at a dosage of 400 mg/d for a period of up to 19 mon
ths. The patients were evaluated clinically for evidence of deteriorat
ion measured by need for hospitalization, development of extrameningea
l disease during the study period, need to reinstitute intrathecal amp
hotericin B therapy because of worsening disease, cerebrospinal fluid
leukocyte count, protein level, and serologic tests for complement-fix
ing antibody. Results: Three patients required hospitalization during
the study, two patients for reasons unrelated to CM. No patient develo
ped extrameningeal disease or required discontinuation of fluconazole
therapy because of deteriorating disease. Patients at exit reported no
symptoms related to meningitis or adverse effects related to fluconaz
ole therapy. There was no deterioration in general health or neurologi
c status. Conclusions: Our study demonstrates that conversion from amp
hotericin B to fluconazole was associated with a stable disease course
of CM for up to 19 months. Further studies delineating both optimal d
osage and characteristics of patients likely to respond to fluconazole
therapy alone are needed.