hilic substances such as phospholipids.
Phospholipids arrange themselves into membrane bilayers when exposed to aqueous solutions.
PK/PD relationship
Mechanism of resistance
Intrinsic resistance, though rare, maybe primarily due to decrease in ergosterol or a change in the target lipid; Leading to reduced binding of amphotericin B to the cell membrane.
Breakpoints
EUCAST breakpoints for AmBisome have not yet been established, however, susceptibility to AmBisome may differ to that of amphotericin B deoxycholate.
Amphotericin B, the antifungal component of AmBisome is active in vitro against many species of fungi., most strains of Histoplasma capsulatum, Coccidioides immitis, Candida spp, Blastomyces dermatidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenkii and Aspergillus fumigatus, Penicillium marneffi, and members of the mucormycetes group of moulds including Mucor mucedo, Rhizomucor and Rhizopus oryzae.
The majority of clinically important fungal species seem to be susceptible to Amphotericin B, although intrinsic resistance has rarely been reported for example, for some strains of S. schenckii, C. glabrata, C.krusei, C. tropicalis, C. lusitaniae, C parapsilosis and Aspergillus terreus.
AmBisome has been shown to be effective in animal models of visceral leishmaniasis (caused by Leishmania infantum and Leishmania donovani).
Clinical Experience
The efficacy of AmBisome has been established in a number of clinical trials for the treatment of systemic mycotic infections, as empirical therapy for fever of unknown origin in neutropenic patients and for the treatment of visceral leishmaniasis. These studies include comparative randomized studies of AmBisome versus conventional amphotericin B in confirmed Aspergillus and Candida infections where the efficacy of both medicinal products was equivalent. In both adult and paediatric febrile neutropenic patients presumed to have fungal infection, the results of a randomized, double-blind clinical trial demonstrated that AmBisome administered at 3 mg/kg/day is as effective as conventional amphotericin B. The efficacy of AmBisome in the treatment of visceral leishmaniasis has been clearly demonstrated in a large population of immunocompetent and immunocompromised patients.
Invasive Filamentous Fungal Infections (IFFI) including Aspergillus spp.: The efficacy of AmBisome has been demonstrated in a prospective, randomised, multicentre study as first line treatment in immunocompromised, mainly neutropenic adults and children (> 30 days old) with proven or probable IFFIs (AmBiLoad Study).
Patients were monitored for 12 weeks. A standard-dose regimen of 3 mg/kg/day (N=107) was compared to a loading dose regimen of 10 mg/kg/day (N=94) for the first 14 days of treatment. The favourable overall response rates were 50% of subjects in the standard-dose group and 46% of the subjects in the loading-dose group in the modified intent-to-treat analysis set. Differences were not statistically significant. The median time to resolution of fever was similar in the standard-dose and loading-dose groups (6 and 5 days, respectively). Twelve weeks after the first dose of AmBisome, survival was 72% in the standard-dose group and 59% in the loading-dose group, a difference that was not statistically significant.
Invasive candidiasis: AmBisome (3 mg/kg/day) was as effective as Micafungin (100 mg/day [Body weight > 40