In vitro Activity of Isavuconazole and Comparators Against Clinical Isolates of Molds from a Multicenter Study in China

Ran Jing; Ian Morrissey; Meng Xiao; Tian-Shu Sun; Ge Zhang; Wei Kang; Da-Wen Guo; Jalal A Aram; Jeffrey Wang; Eric A Utt; Yao Wang; Ying-Chun Xu

doi:10.2147/IDR.S360191

In vitro Activity of Isavuconazole and Comparators Against Clinical Isolates of Molds from a Multicenter Study in China

Infect Drug Resist. 2022 Apr 22:15:2101-2113. doi: 10.2147/IDR.S360191. eCollection 2022.

Authors

Ran Jing^{1

2

3}, Ian Morrissey⁴, Meng Xiao^{1

3}, Tian-Shu Sun^{3

5}, Ge Zhang^{1

3}, Wei Kang^{1

3}, Da-Wen Guo⁶, Jalal A Aram⁷, Jeffrey Wang⁸, Eric A Utt⁷, Yao Wang^{1

3}, Ying-Chun Xu^{1

2

3}

Affiliations

¹ Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
² Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
³ Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People's Republic of China.
⁴ IHMA Europe Sarl, Monthey, Valias, Switzerland.
⁵ Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
⁶ Department of Laboratory Medicine, the First Clinical Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
⁷ Medical Affairs, Pfizer Inc, Groton, CT, USA.
⁸ Clinical Development, Pfizer, Beijing, People's Republic of China.

Abstract

Purpose: Monitoring antifungal susceptibility patterns for new or established antifungals is imperative. Antifungal resistance is frequent in molds, frequently leading to invasive mold infections (IMIs) in immunocompromised patients with high morbidity and mortality. Limited availability of effective antifungals for treatment of IMIs in China is an enormous challenge. The purpose of this study was to monitor in vitro antifungal resistance profiles of mold isolates from China, with a particular focus on evaluating in vitro isavuconazole (ISA) activity against these isolates, contributing to the treatment guidance in clinics.

Methods: We evaluated the in vitro activity of ISA and its comparators (voriconazole [VOR] and amphotericin B [AMB]) against 131 clinical isolates of Aspergillus spp. (n = 105) and Mucorales order (n = 26) collected between 2017 and 2020 from China.

Results: ISA and VOR exhibited similar in vitro activity against Aspergillus spp., with minimum inhibitory concentration (MIC)₅₀ of 1 µg/mL and MIC₉₀ of 2 µg/mL, respectively. Overall, AMB was less active than azoles against Aspergillus spp. (MIC₅₀: 4 µg/mL, MIC₉₀: 8 µg/mL). Against the Mucorales order, ISA demonstrated MIC₅₀ of 0.5 µg/mL and MIC₉₀ of 1 µg/mL; however, one strain each of Mucor circinelloides and Syncephalastrum racemosum were resistant to ISA (MICs: >8 µg/mL). VOR exhibited little or no activity (MIC₅₀: 8 µg/mL, MIC₉₀: >8 µg/mL) against the Mucorales order, whereas AMB had MIC₅₀ and MIC₉₀ of 1 µg/mL.

Conclusion: This was the first multicenter, in vitro study conducted in China and demonstrated the excellent activities of ISA against most species of the Mucorales order. MIC indicated an advantage over currently available azole antifungals, positioning ISA as a potential alternative to VOR for clinical management of IMIs. As with other antimicrobials, clinicians should employ stewardship and best practices in relation to potential resistance to new azole antifungals.

Keywords: Aspergillus species; Mucorales order; antifungal susceptibility testing; isavuconazole; resistance.

Grants and funding

This work was supported by the Pfizer Inc., Special Foundation for National Science and Technology Basic Research Program of China [grant number: 2019FY101204], Fundamental Research Funds for the Central Universities [grant number: 3332020005], and the Beijing Key Clinical Specialty for Laboratory Medicine Excellent Project [grant number: ZK201000]. Sponsors have no role in any of the stages from study design to submission of the paper for publication.