Single High-Dose Liposomal Amphotericin-based Therapy
CRYPTOCOCCAL MENINGITIS
The AMBITION phase 2 trial was a multisite, randomized, controlled trial with the objective of finding the optimal high-dose, short-course AmBisome dosing strategy for cryptococcal meningitis [Eighty participants were enrolled before the study was stopped on recommendation of the independent data and safety monitoring committee. The antifungal activity was similar across the 3 short-course, high-dose AmBisome arms, which were all noninferior to the control 14-day regimen (EFA of single dose: −0.52 logAt that time, the ACTA trial results became available showing the superiority of flucytosine as a partner drug with amphotericin. There were, however, concerns that if we simply switched to a single-dose AmBisome plus flucytosine combination, low levels of AmBisome could effectively result in flucytosine monotherapy toward the end of the induction period, risking the development of flucytosine resistance given its low barrier to resistance. Adding single-dose AmBisome to the optimized oral backbone of high-dose fluconazole plus flucytosine, which even on its own performed well in the ACTA trial, would protect flucytosine while giving a needed amphotericin-related fungicidal boost to the oral regimen. In addition, prior phase 2 studies [