353. Evaluation of the in vitro activity of amphotericin B used in the liposomal formulation AmBisome against contemporary human fungal pathogens
Authors: Zaragoza Oscar , Investigator Principal , Merino-Amador Teresa , de Armentia Cristina , Lass-Flörl Cornelia , Buil Jochem B , Verweij Paul E , Woo Patrick C Y , Tsang Chi-Ching , Lewis White P , Price Jessica , Grimes Carolyn , Ostrosky-Zeichner Luis , Pasqualotto Alessandro C , Cuenca-Estrella Manuel 
Published: December 2022

Abstract

Background
Amphotericin B is an antifungal drug whose main limitation is toxicity. To reduce these side effects, liposomal formulations have been developed, being AmBisome (L-AmB, Gilead Science Inc) the most commonly used. We describe the in vitro antifungal activity of L-AmB component used in the AmBisome formulation

Methods
We performed a multicenter study to determine the susceptibility to L-AmB using CLSI and EUCAST reference methods. Contemporary human fungal pathogenic species (14 yeast spp and 23 mould spp from different geographical regions were included. Other antifungals (triazoles and echinocandins) were also evaluated.

Results
L-AmB showed activity against yeast species using both EUCAST and CLSI protocols. The strongest activity was shown against Candida albicans (GM-EUCAST 0.24 mg/L (n=85), CLSI 0.23 mg/L (n=111)), C. parapsilosis (GM-EUCAST 0.32 mg/L (n=82), CLSI 0.32 mg/L (n=124)), C. glabrata (GM-EUCAST 0.32 mg/L (n=84), CLSI 0.38 mg/L (n=145)), C. auris (GM-EUCAST 0.46 mg/L (n=20), CLSI 0.31 mg/L (n=22)). In filamentous fungi, lowest MICs were found for Aspergillus fumigatus (GM-EUCAST 0.62 mg/L (n=77), CLSI 0.65 mg/L (n=124)), and A. niger (GM-EUCAST 0.25 mg/L (n=72) , CLSI 0.32 mg/L (n=85)), while for other Aspergillus species, there was a higher variability in the MICs (A. flavus, GM-EUCAST 1.2 mg/L (n=71), CLSI 1.75 mg/L (n=76); A. terreus GM-EUCAST 1.7 mg/L (n=65), CLSI 1.04 mg/L (n=71); A. nidulans GM-EUCAST 1.38 mg/L (n=39), CLSI 0.73 mg/L (n=39)). For other genera from filamentous fungi, L-AmB had a strong activity (GM around 0.2-0.5 mg/L for both methods, including Talaromyces marneffei, Rhizopus arrhizus and R. microscoporus, Lichtheimia corymbifera, Mucor circinelloides). The less susceptible species corresponded to multi-resistant (MDR) species, such as Lomentospora prolificans and Cunninghamella bertholletiae.

Conclusion
The L-AmB component of AmBisome showed activity against most contemporary human fungal pathogens and only showed limited activity against some MDR mould species.

Disclosures
Oscar Zaragoza, Principal Investigator, Gilead: Grant/Research Support Teresa Merino-Amador, n/a, Gilead: Grant/Research Support Cristina de Armentia, n/a, Gilead: Grant/Research Support Cornelia Lass-Flörl, PhD, Gilead: Grant/Research Support Jochem B. Buil, PhD, Gilead: Grant/Research Support Paul E. Verweij, PhD, Gilead: Grant/Research Support Patrick C. Y. Woo, PhD, Gilead: Grant/Research Support Chi-Ching Tsang, PhD, Gilead: Grant/Research Support P. Lewis White, PhD, Associates of Cape Cod: Honoraria|F2G: Advisor/Consultant|Gilead: Grant/Research Support|IMMY: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Jessica Price, PhD, Gilead: Grant/Research Support Carolyn Grimes, PhD, Gilead: Grant/Research Support Alessandro C. Pasqualotto, PhD, Gilead: Grant/Research Support Manuel Cuenca-Estrella, PhD, Gilead: Grant/Research Support.