Dose response evaluation of fluconazole in coccidioidal meningitis, a preliminary evaluation

Johnson, R. H.;Caldwell, J. W.;Williams, P. L.;Einstein, H. E.


Recently published data demonstrating the efficacy of Fluconazole (F) for coccidioidal meningitis (CM) by the NIAID Mycosis Study Group (MSG) prompted a retrospective evaluation of our experience with patients initially treated with (F) since 1991. Fifty patients from the coccidioidomycosis clinic at Kern Medical Center and the private practices of two investigators were identified for review.Two evaluable groups were identified for comparison who received greater than 3 months treatment at a stable dose. Group I (F-400) consisted of 16 patients treated initially with 400 mg/day for a mean duration of 219 days. Group II (F-800) consisted of 18 patients initially treated with 800 to 1600 mg for a mean duration of 276 days. A third non-evaluable group included 16 patients that did not receive stable dosing or a minimum duration of 3 months. There were no differences in the two patient groups in age, sex, race, or skin test. The unevaluable group had a greater co-morbidity of diabetes.The F-400 and F-800 groups were compared using the MSG-scoring system. Initial baseline scores were 7.81 for the F-400 group and 7.00 for the F-800 group. The F-800 group responded with a mean score of 3.6 (mean duration of 276 days). However, the F 400 group only dropped to 6.5 (mean duration 219 days). A mean score of 3.8 in the F-800 group at 180 days was nearly identical to the 276 day score, suggesting that dose was more important than duration of treatment. Patients with a 40 percent decrease from baseline score were considered responders. Five of 16 (31 percent) in the F 400 group responded, compared to 12 of 18 (67 percent) in the F-800 group (p = 0.04 chi-square). There was one death in each evaluable treatment group. Of the 16 patients in the unevaluable group, there were 3 responders, 7 early deaths, and 6 non-responders. Eleven patients were started on 400 mg and five on 800 mg or greater.Compared with 400 mg, initial doses equal to or greater than 800 mg of fluconazole in coccidioidal meningitis are associated with an improved early response. Evaluation at 1 and 2 years of treatment are necessary to assess the long-term efficacy.

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Full conference title: 

Coccidioidomycosis - Centennial Conference
    • Coccidioidomycosis