2114. Evaluation of Isavuconazole Activity against Non-fumigatus Aspergillus and cryptic Aspergillus species Causing Invasive Infections Worldwide
Authors: Carvalhaes Cecilia G , Rhomberg Paul , Kantro Valerie , Hatch Beth , Castanheira Mariana 
Published: November 2023

Abstract

Background
Isavuconazole (ISC) is considered first-line therapy for the treatment of invasive aspergillosis (IA). There is limited data on antifungal susceptibility testing of clinically relevant non-fumigatus (non-AFM) and cryptic species of Aspergillus (cryAsp) causing IA. The activity of ISC and other azoles against non-AFM and cryAsp causing IA worldwide was evaluated.

Methods
A total of 390 non-AFM, including 63 cryAsp isolates, were collected (1/patient) in 2017–2021 from 41 medical centers located in Europe (EU; n=161; 17 centers), North America (NA; n=137; 16 centers), Asia-Pacific (AP; n=85; 7 centers), and Latin America (LA, n=7; 1 center). Isolates were identified by MALDI-TOF MS and/or ITS/β-tubulin sequencing and tested by CLSI broth microdilution. CLSI epidemiological cut-off values were applied, where available.

Results
ISC showed activity against A. sections Flavi (n=122; MIC50/90, 0.5-1 mg/L), Terrei (n=57; MIC50/90, 0.5/0.5 mg/L), Nidulans (n=34; MIC50/90, 0.12/0.25 mg/L), Versicolores (n=7; MIC50, 1 mg/L), and Circumdati (n=2; MIC range, 0.12–2 mg/L). Similar activity was displayed by other azoles against those Aspergillus sections. Most of the isolates from A. sections Fumigati (n=9), Nigri (n=146), and Usti (n=12) exhibited elevated MIC values to ISC (MIC50/90, 2/8, 2/4, and 2/8 mg/L), VRC (MIC50/90, 2/8, 1/2, and 4/8 mg/L), ITC (MIC50/90, 2/4, 2/4, and 8/ &gt; 8 mg/L), and PSC (MIC50/90, 0.5/1, 0.5/1, and &gt; 8/ &gt; 8 mg/L), respectively. The activity of ISC and other azoles against cryAsp, A. niger and A. terreus, when identified to the species level, are listed in the Table. ISC was active (MIC values, ≤ 1 mg/L) against A. parasiticus, A. tamarii, A. nomius, A. nidulans, A. unguis, A. terreus, A. alabamensis, and A. hortai, while ISC MIC values between 2–8 mg/L were observed against cryAsp from A. section Fumigati. ISC inhibited 96.1% of A. niger and 80.0% of A. tubingensis at ≤ 4 mg/L, the CLSI wildtype cut-off value for A. niger. VRC, ITC, and PSC showed similar activity to ISC against most cryAsp.

Conclusion
ISC exhibited potent in vitro activity against non-AFM, including cryAsp. However, the activity of ISC and other azoles vary among and within cryAsp species. Susceptibility testing is critical to guide treatment of cryAsp causing IA.

Disclosures
Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), bioMerieux: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Valerie Kantro, BA, AbbVie: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Beth Hatch, BS, MT(ASCP), Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support