Efficacy of LAMB against Emerging Azole- and Multidrug-Resistant Isolates in the Model.

While being the third leading cause of candidemia worldwide, numerous studies have shown severe clonal outbreaks due to fluconazole-resistant (FLCR) isolates associated with fluconazole therapeutic failure (FTF) with enhanced mortality. More recently, multidrug resistant (MDR) blood isolates have also been identified that are resistant to both azole and echinocandin drugs. Amphotericin B (AMB) resistance is rarely reported among isolates and proper management of bloodstream infections due to FLZR and MDR isolates requires prompt action at the time of outbreak. Therefore, using a well-established model, we assessed whether (a) laboratory-based findings on azole or echinocandin (micafungin) resistance in lead to therapeutic failure, (b) LAMB could serve as an efficient salvage treatment option, and (c) distinct mutations in impact mortality. Our in vivo data confirm fluconazole inefficacy against FLCR isolates carrying Y132F, Y132F + K143R, Y132F + G307A, and G307A + G458S in Erg11p, while LAMB proved to be an efficacious accessible option against both FLCR and MDR isolates. Moreover, positive correlation of in vitro and in vivo data further highlights the utility of as a reliable model to investigate azole and polyene drug efficacy.