TY - JOUR
T1 - Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals
AU - Vahedi-Shahandashti, Roya
AU - Houbraken, Jos
AU - Birch, Mike
AU - Lass-Flörl, Cornelia
N1 - Funding Information:
The present study was funded by Austrian Science Fund, HOROS W1253-B24.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/6/6
Y1 - 2023/6/6
N2 - The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number of antifungal medications available for treating IFIs, and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, are increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity, namely, manogepix, rezafungin, ibrexafungerp, and olorofim, against 100 isolates of Aspergillus section Terrei, containing amphotericin-B (AmB)-wildtype/non-wildtype and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against the tested isolates, exhibiting geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentration (MIC) ranges, respectively, as follows: manogepix (0.048 mg/L, 0.032–0.5 mg/L), rezafungin (0.020 mg/L, 0.016–0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032–2 mg/L), and olorofim (0.008 mg/L, 0.008–0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species.
AB - The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number of antifungal medications available for treating IFIs, and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, are increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity, namely, manogepix, rezafungin, ibrexafungerp, and olorofim, against 100 isolates of Aspergillus section Terrei, containing amphotericin-B (AmB)-wildtype/non-wildtype and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against the tested isolates, exhibiting geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentration (MIC) ranges, respectively, as follows: manogepix (0.048 mg/L, 0.032–0.5 mg/L), rezafungin (0.020 mg/L, 0.016–0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032–2 mg/L), and olorofim (0.008 mg/L, 0.008–0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species.
KW - antifungal susceptibility test
KW - aspergillosis
KW - Aspergillus terreus
KW - EUCAST
KW - ibrexafungerp
KW - manogepix
KW - new antifungals
KW - olorofim
KW - resistance
KW - rezafungin
UR - http://www.scopus.com/inward/record.url?scp=85163722298&partnerID=8YFLogxK
U2 - 10.3390/jof9060649
DO - 10.3390/jof9060649
M3 - Article
AN - SCOPUS:85163722298
SN - 2309-608X
VL - 9
SP - 1
EP - 9
JO - Journal of Fungi
JF - Journal of Fungi
IS - 6
M1 - 649
ER -