P-1096. Activity of Ibrexafungerp and Comparator Antifungals Tested against Candida and Aspergillus Isolates Collected from Invasive Infections in a Global Surveillance Program in 2023

Abstract

Background

Ibrexafungerp (IBX) is a novel triterpenoid antifungal agent that was approved by the U.S. FDA for the treatment of vulvovaginal candidiasis (VVC) in 2021. Further studies are ongoing to assess the efficacy of IBX for the treatment of invasive candidiasis (IC) and other refractory fungal infections, including aspergillosis. CLSI, EUCAST, or FDA clinical breakpoints or epidemiological cutoff values are not yet defined for IBX against fungi. We evaluated the activity of IBX and comparator agents against clinical isolates from IC and invasive aspergillosis infections collected from a global surveillance program in 2023.

MIC50/90 (mg/L) for ibrexafungerp (IBX) and comparator agents against 5 most common Candida spp., C. auris, and 3 most common Aspergillus spp. in 2023 SENTRY Antifungal Surveillance Program

Methods

A total of 1120 Candida spp. and 204 Aspergillus spp. isolates consecutively collected as part of the SENTRY Program were evaluated. Isolates were recovered from 11 medical centers in North America, 18 in Europe, 7 in Asia-Pacific, and 5 in Latin America. Identification was performed by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method for IBX, anidulafungin (AND), micafungin (MFG), fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC).

Results

Table 1 displays MIC_50/90 results for the 5 most common Candida spp., C. auris, and the 3 most common Aspergillus spp. The IBX MIC_50/90 results were low against all organisms including organisms of critical concern like C. auris. Among Candida species, IBX had similar or higher MIC_50/90 to AND except for C. parapsilosis where IBX MIC_50/90 values were 4- to 8-fold lower. MFG was more potent (4- to 16-fold) against most Candida spp. except for C. parapsilosis where IBX had 2-to 4- fold lower MIC_50/90 and C. auris where IBX was similar to MFG. Notably, the highest MIC result observed for IBX against C. auris was 1 mg/L. MIC_50/90 values for IBX were also 8- to > 256-fold lower than azoles against Aspergillus spp. but higher (2- to ≥ 16-fold) than MFG or AND.

Conclusion

IBX has good activity against the predominant Candida and Aspergillus species from a worldwide contemporary collection. This agent may represent an oral option for the management of difficult-to-treat invasive fungal pathogens such as C. glabrata, C. auris, and Aspergillus spp. from diverse infection sources in addition to its current indication for VVC.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support Sharon Min, MS, GSK: Employee