In Vitro Antifungal Activity of Manogepix and Other Antifungal Agents against South African Candida auris Isolates from Bloodstream Infections

Abstract

Since C. auris was first detected in South Africa in 2009, health care-associated transmission events and large outbreaks have led to this pathogen accounting for more than 1 in 10 cases of candidemia. A large proportion of South African C. auris isolates are highly resistant to fluconazole but variably resistant to amphotericin B and echinocandins.

Heightened efficacy of anidulafungin when used in combination with manogepix or 5-flucytosine againstCandida auris in vitro

“…None of these studies included manogepix. Both manogepix and 5-flucytosine have potent antifungal activity against C. auris as shown here and observed by others (39)(40)(41)(42)(43)(44).…”

Candida auris in Austria—What Is New and What Is Different

“…In particular, manogepix showed potent in vitro activity with MIC values of 0.008–0.032 mg/L. This supports the assumption that manogepix could be a valuable therapeutic alternative in the treatment of C. auris [ 44 , 45 , 46 ].…”

Overestimation of Amphotericin B Resistance in Candida auris with Sensititre YeastOne Antifungal Susceptibility Testing: a Need for Adjustment for Correct Interpretation

“…Overall, unimodal CLSI AMB MIC distributions have been described implying a low rate of resistance of C. auris isolates ( 11 , 26 , 27 ), as was also shown by a recent meta-analysis of the global epidemiology of this yeast (12% AMB resistance rate) ( 16 ). However, when Maphanga et al assessed the susceptibility of 394 South African C. auris bloodstream isolates using SYO, they reported a resistance rate of 27%, based on the CDC’s tentative breakpoint (modal MIC, MIC 50 , and MIC 90 values of 1 mg/L, 1 mg/L, and 2 mg/L, respectively) ( 18 ). Intriguingly, when the AMB MICs were redetermined using gradient concentration strips (Etest), the resistance rate decreased to 6%, thereby highlighting the method variability with AMB AFST as well as the need for setting method-specific ECOFFs.…”

“…However, in the context of the emergence of breakthrough C. auris infections as well as the therapeutic failures observed among patients treated with echinocandins ( 3 , 4 , 14 , 15 ) in conjunction with the high (91%) resistance rate of C. auris to fluconazole ( 16 ), treatment with liposomal AMB could be considered as an alternative therapeutic option ( 17 ). A recent meta-analysis revealed a relatively low AMB resistance rate of 12% among C. auris isolates ( 16 ), whereas resistance up to 27% and 50% was observed with the SYO assay ( 18 ) and the Etest strips ( 19 ), respectively. Despite the elevated MICs (>1 mg/L), resistance could not be confirmed molecularly, as no mutations within the ERG3 , ERG5 , ERG6 , and/or ERG10 genes that have been associated with resistance to AMB in Candida species have been detected ( 20 , 21 ).…”