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Published on: March 22, 2012
In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic
Olga Rivero-Menendez1, Juan Carlos Soto-Debran1, Manuel Cuenca-Estrella1,2
1National Centre for Microbiology, Mycology Reference Laboratory, Instituto de Salud Carlos III, 28222 Madrid, Spain.
Abstract:
Ibrexafungerp is a new orally-available 1,3-β-D-glucan synthesis inhibitor in clinical development. Its in vitro activity and that of amphotericin B, voriconazole, and micafungin were evaluated against a collection of 168 clinical isolates of Aspergillus spp., including azole-susceptible and azole-resistant (Cyp51A mutants) Aspergillus fumigatus sensu stricto (s.s.) and cryptic species of Aspergillus belonging to six species complexes showing different patterns of antifungal resistance, using EUCAST and CLSI antifungal susceptibility testing reference methods. Ibrexafungerp displayed low geometric means of minimal effective concentrations (MECs) against A. fumigatus s.s. strains, both azole susceptible (0.040 mg/L by EUCAST and CLSI versus 1.231 mg/L and 0.660 mg/L for voriconazole, respectively) and azole resistant (0.092 mg/L and 0.056 mg/L, EUCAST and CLSI, while those for voriconazole were 2.144 mg/L and 2.000 mg/L). Ibrexafungerp was active against most of the cryptic species of Aspergillus tested, yielding MEC values only comparable to those of micafungin. Nevertheless, this new compound exhibited a moderate activity against A. ustus complex species, MECs ≥ 0.5 mg/L against Aspergillus insuetus and Aspergillus keveii strains, and was inactive against the Aspergillus alliaceus isolates tested (MEC90s ≥ 16 mg/L). All in all, ibrexafungerp shows encouraging in vitro results against cryptic species of Aspergillus and azole-susceptible and azole resistant strains of A. fumigatus, some of which are difficult to treat using the available therapeutic options.
Insights
Ibrexafungerp shows promising in vitro antifungal activity against Aspergillus fumigatus, including resistant strains. This new glucan synthesis inhibitor also demonstrated effectiveness against various cryptic Aspergillus species, offering potential new treatment options.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Emerging drug resistance in Aspergillus species poses a significant clinical challenge.
- Novel antifungal agents are crucial for combating difficult-to-treat invasive aspergillosis.
- Ibrexafungerp is an orally available 1,3-β-D-glucan synthesis inhibitor under clinical development.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of ibrexafungerp against a diverse panel of Aspergillus clinical isolates.
- To compare ibrexafungerp's efficacy with established antifungals like amphotericin B, voriconazole, and micafungin.
- To assess ibrexafungerp's activity against both azole-susceptible and azole-resistant Aspergillus fumigatus, including cryptic species.
Main Methods:
- Antifungal susceptibility testing was performed using EUCAST and CLSI reference methods.
- 168 clinical isolates of Aspergillus spp. were tested, encompassing Aspergillus fumigatus sensu stricto and various cryptic species.
- Minimal Effective Concentrations (MECs) were determined for ibrexafungerp, amphotericin B, voriconazole, and micafungin.
Main Results:
- Ibrexafungerp exhibited low MECs against azole-susceptible and azole-resistant Aspergillus fumigatus strains, outperforming voriconazole.
- The compound showed activity against most tested cryptic Aspergillus species, with efficacy comparable to micafungin.
- Moderate activity was observed against Aspergillus ustus complex species, while ibrexafungerp was inactive against Aspergillus alliaceus isolates.
Conclusions:
- Ibrexafungerp demonstrates encouraging in vitro activity against key Aspergillus species, including challenging azole-resistant and cryptic strains.
- Its efficacy suggests potential as a valuable therapeutic option for invasive aspergillosis, particularly in cases with limited treatment alternatives.
- Further clinical investigation is warranted to confirm ibrexafungerp's therapeutic potential in treating Aspergillus infections.
