347. Azole Activity against Filamentous Fungi Causing Invasive Infections in Patients from ICU and Non-ICU Units (2017-2021)

BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality rates in critically ill patients. Appropriate antifungal treatment is crucial for managing IFI. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against contemporary moulds from ICU and non-ICU patients. [Figure: see text] METHODS: 1,226 moulds causing IFI (386/840 from ICU/non-ICU patients, respectively) were consecutively collected (1/patient) in 43 worldwide hospitals from 2017-2021 and susceptibility tested by CLSI broth microdilution. CLSI interpretation criteria were applied. Pneumonia was the predominant infection type among ICU (81.6%) and non-ICU (71.8%) patients. RESULTS: Aspergillus spp. was the most common mould (87.6%/80.5%). A. fumigatus (AFM; 76.0%/65.4% of Aspergillus), A. section Flavi (ASF; 9.2%/10.9%), and A. section Nigri (ASN; 7.4%/13.6%) were the top 3 Aspergillus groups. ISC inhibited 94.2%/91.2%, 100.0%/98.6%, and 96.0%/96.7% of AFM, ASF, and ASN from ICU/non-ICU, respectively, at the epidemiological cut-off values. Similar activities were noted for ISC, PSC, ITC, and VRC against AFM from ICU (MIC(50/90) range, 0.25-1/0.5-1 mg/L) and non-ICU (MIC(50/90) range, 0.5-1/0.5-2 mg/L) isolates. No difference in the azole activities was noted against ASF from ICU (MIC(50/90) range, 0.5/0.5-1 mg/L) and non-ICU (MIC(50/90), 0.5/0.5-1 mg/L) or ASN from ICU (MIC(50/90) range, 0.5-2/1-4 mg/L) and non-ICU (MIC(50/90) range, 0.5-2/1-4 mg/L) isolates. VRC-non-susceptible (NS) AFM isolates were detected in 9.3% of ICU and 9.0% of non-ICU isolates. Among VRC-NS AFM from ICU/non-ICU, 58.3%/27.5% were wildtype (WT) to ISC, 50.0%/25.0% were ITC-WT, and 75.0%/50.0% remained VRC-WT, respectively. VRC was the most active azole against Scedosporium spp. (SCE) but was less active against Mucorales (MUC) than the other azoles. All azoles showed limited activity against Fusarium spp. (FUS). No difference on azole activities against SCE, MUC, and FUS were noted from ICU and non-ICU isolates. CONCLUSION: ISC was active against Aspergillus isolates from ICU and non-ICU, including against VRC-NS AFM from ICU. Azoles displayed similar activity against moulds from ICU and non-ICU units. DISCLOSURES: Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Beth A. Schaefer, BA, MT(ASCP), Pfizer: Grant/Research Support Michael A. Pfaller, MD, Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.