Fungicidal Activity
cryptococcal meningitis, EFA
CRYPTOCOCCAL MENINGITIS
In terms of fungicidal activity, the AMBITION phase 3 trial demonstrated that the EFA of the single, high-dose AmBisome regimen was no different from that achieved with 7 days of amphotericin deoxycholate–based treatment. Also, the AMBITION phase 2 data show that the single, high-dose regimen is noninferior and may be marginally superior in EFA to standard daily AmBisome dosing for 14 days. Although the number of patients treated was small, the EFA was more rapid than control daily dosing across the 3 intermittent dosing arms (−0.52, −0.47, and −0.54 for 1, 2, and 3 doses, respectively, compared with daily −0.41 logHamill et al’s trial is the only one to provide data on the sterilizing effect of daily AmBisome for 14 days in high-income settings [While there is no large, randomized trial comparison, it is plausible that daily 3–4 mg/kg/d AmBisome is less active in terms of EFA than either amphotericin deoxycholate at 1 mg/kg/d or the AMBITION single, high-dose regimen, with no data to suggest that 3–4 mg/kg/d AmBisome would be more fungicidal. We would contend that overall the evidence suggests that the AMBITION triple-therapy regimen would have at least equivalent fungicidal activity as 14 days of daily 3–4 mg/kg AmBisome plus flucytosine and should not be regarded as a compromise regimen of interest only in resource-limited settings in terms of antifungal effect (The use of single-dose AmBisome based treatment for cryptococcal meningitis in high-income settings.