1148. Activity of Posaconazole and Comparator Antifungal agents Tested Against Filamentous Fungi
Authors: Castanheira Mariana , Carvalhaes Cecilia G , Motyl Mary , Han Seongah , Campbell Havilland 
Published: January 2021

Abstract

Background
Posaconazole (POS) is a broad-spectrum triazole antifungal that exhibits potent antifungal activity against a variety of yeasts and molds. We evaluated the in vitro activities of posaconazole and comparator antifungal agents against 2,554 isolates of filamentous fungi including 2,100 Aspergillus species and 454 non-Aspergillus moulds (98 Fusarium, 81 Mucorales and 76 Scedosporium species isolates) collected worldwide in 2010-2018 from clinically significant infections.

Methods
Isolates were identified using sequencing and/or MALDI-TOF MS methods. Posaconazole, itraconazole, voriconazole, caspofungin, anidulafungin, micafungin, and amphotericin B were tested using the reference broth microdilution method according to CLSI guidelines.

Results
Posaconazole showed comparable activity to itraconazole and voriconazole against A. fumigatus. Categorical agreement between posaconazole and the other azoles tested against A. fumigatus ranged from 98.2-98.7%. Most of the Aspergillus species isolates tested (&gt;90%) were WT to all azoles and echinocandins. Among the isolates of A. fumigatus, the rate of NWT strains varied across the different geographic regions. The frequency of azole NWT strains of A. fumigatus from Europe increased steadily from 2010 to 2018. There was no consistent trend for an increased frequency of NWT strains from other geographic areas. The azoles and echinocandins showed poor activity against Fusarium and Scedosporium species. Posaconazole (MIC50/90, 1/2 mg/L) and amphotericin B (MIC50/90, 1/2 mg/L) were the most active agents against the Mucorales isolates.

Conclusion
Posaconazole exhibited excellent activity against most species of Aspergillus and was comparable to itraconazole and voriconazole. Most Aspergillus species remain susceptible to triazoles. Although there was no evidence for an increasing frequency of NWT strains among A. fumigatus isolates from North America, Latin America or the Asia-Pacific region, we confirm an increase in the rate of NWT strains to all three triazoles among isolates from Europe.

Disclosures
Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Seongah Han, PhD, Merck & Co, Inc. (Employee) Havilland Campbell, BS, Merck & Co, Inc. (Employee)