2114. Evaluation of Isavuconazole Activity against Non-fumigatus Aspergillus and cryptic Aspergillus species Causing Invasive Infections Worldwide

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. [Figure: see text] 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; MIC(50/90), 0.5-1 mg/L), Terrei (n=57; MIC(50/90), 0.5/0.5 mg/L), Nidulans (n=34; MIC(50/90), 0.12/0.25 mg/L), Versicolores (n=7; MIC(50), 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 (MIC(50/90), 2/8, 2/4, and 2/8 mg/L), VRC (MIC(50/90), 2/8, 1/2, and 4/8 mg/L), ITC (MIC(50/90), 2/4, 2/4, and 8/ > 8 mg/L), and PSC (MIC(50/90), 0.5/1, 0.5/1, and > 8/ > 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