How would you approach treatment in a patient with refractory Coccidioidal meningitis who has previously been treated with IV amphotericin B?

The previous receipt of amphotericin B is irrelevant. Shortly after its introduction in the mid-1950s, it was recognized that it was ineffective in the treatment of coccidioidal meningitis when given intravenously and that intrathecal administration was necessary (Winn, PMID 14065439). The introduction of azole antifungal agents obviated the need for amphotericin B and altered the approach and although still occasionally used, intrathecal amphotericin B is now relegated to a treatment of last resort.

The answer to the question depends upon knowledge of the treatments that have failed and the nature of the failure. The recommended first-line therapy is fluconazole, with an alternative azole (e.g., voriconazole, posaconazole) substituted if it...