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Published on: February 14, 2018
In vitro Activity of Isavuconazole and Comparators Against Clinical Isolates of Molds from a Multicenter Study in
Ran Jing1,2,3, Ian Morrissey4, Meng Xiao1,3
1Department 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.
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.
Insights
Isavuconazole shows excellent in vitro activity against Mucorales, offering a potential alternative for invasive mold infections. This study monitored antifungal resistance in China, highlighting the need for antimicrobial stewardship.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Antifungal resistance in molds poses a significant threat, particularly for immunocompromised patients with invasive mold infections (IMIs).
- Limited effective antifungal options in China present a clinical challenge for treating IMIs.
- Monitoring antifungal susceptibility is crucial for guiding treatment strategies.
Purpose of the Study:
- To assess in vitro antifungal resistance profiles of mold isolates from China.
- To evaluate the in vitro activity of isavuconazole (ISA) against these clinical isolates.
- To inform clinical treatment guidelines for IMIs in China.
Main Methods:
- In vitro evaluation of isavuconazole (ISA), voriconazole (VOR), and amphotericin B (AMB) activity.
- Testing against 131 clinical mold isolates from China (2017-2020): 105 Aspergillus spp. and 26 Mucorales.
- Determination of minimum inhibitory concentrations (MICs) for each isolate and antifungal.
Main Results:
- Isavuconazole and voriconazole demonstrated similar in vitro activity against Aspergillus spp. (MIC50: 1 µg/mL, MIC90: 2 µg/mL).
- Isavuconazole showed potent activity against Mucorales (MIC50: 0.5 µg/mL, MIC90: 1 µg/mL), with resistance in two strains.
- Amphotericin B was less active against Aspergillus spp. than azoles, while voriconazole had limited activity against Mucorales.
Conclusions:
- Isavuconazole exhibits excellent in vitro activity against most Mucorales species, suggesting it as a potential alternative to voriconazole for IMIs.
- This study is the first multicenter in vitro assessment in China, providing valuable data on mold antifungal resistance.
- Prudent antimicrobial stewardship is essential to mitigate the development of resistance to new antifungals.
