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Published on: April 19, 2017
Evaluation of the Activity of Triazoles Against Non-fumigatus Aspergillus and Cryptic Aspergillus Species Causing
Michael A Pfaller1,2, Cecilia G Carvalhaes1, Paul R Rhomberg1
1JMI Laboratories, North Liberty, Iowa, USA.
Abstract:
The activity of isavuconazole and other triazoles against non-fumigatus (non-AFM) Aspergillus causing invasive aspergillosis was evaluated. A total of 390 non-AFM isolates were collected (1/patient) in 2017-2021 from 41 hospitals. Isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and/or internal spacer region/β-tubulin sequencing and tested by Clinical and Laboratory Standards Institute (CLSI) broth microdilution. CLSI epidemiological cutoff values were applied, where available. Isavuconazole showed activity against Aspergillus sections Flavi (n = 122; minimum inhibitory concentration [MIC]50/90, 0.5/1 mg/L), Terrei (n = 57; MIC50/90, 0.5/0.5 mg/L), Nidulantes (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 triazoles against those Aspergillus sections. Most of the isolates from Aspergillus sections Fumigati (n = 9), Nigri (n = 146), and Usti (n = 12) exhibited elevated MIC values to isavuconazole (MIC50/90, 2/-, 2/4, and 2/8 mg/L), voriconazole (MIC50/90, 2/-, 1/2, and 4/8 mg/L), itraconazole (MIC50/90, 2/-, 2/4, and 8/>8 mg/L), and posaconazole (MIC50/90, 0.5/-, 0.5/1, and >8/>8 mg/L), respectively. Isavuconazole was active (MIC values, ≤1 mg/L) against Aspergillus parasiticus, Aspergillus tamarii, Aspergillus nomius, Aspergillus nidulans, Aspergillus unguis, Aspergillus terreus, Aspergillus alabamensis, and Aspergillus hortai, while isavuconazole MIC values between 2 and 8 mg/L were observed against cryptic isolates from Aspergillus section Fumigati. Isavuconazole inhibited 96.1% of Aspergillus niger and 80.0% of Aspergillus tubingensis at ≤4 mg/L, the CLSI wild-type cutoff value for A niger. Voriconazole, itraconazole, and posaconazole showed similar activity to isavuconazole against most cryptic species. Isavuconazole exhibited potent in vitro activity against non-AFM; however, the activity of triazoles varies among and within cryptic species.
Insights
Isavuconazole demonstrates potent in vitro activity against non-fumigatus Aspergillus species causing invasive aspergillosis. However, triazole antifungal activity varies significantly among different cryptic species and within species groups.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Invasive aspergillosis is a serious fungal infection, often caused by non-fumigatus Aspergillus (non-AFM) species.
- Evaluating the in vitro activity of antifungals like isavuconazole against these diverse species is crucial for effective treatment.
Purpose of the Study:
- To assess the in vitro activity of isavuconazole and other triazoles against a collection of non-AFM Aspergillus isolates.
- To compare the susceptibility patterns of different Aspergillus sections and cryptic species to these antifungals.
Main Methods:
- Collected 390 non-AFM Aspergillus isolates from 41 hospitals between 2017-2021.
- Identified isolates using MALDI-TOF MS and/or gene sequencing.
- Determined antifungal susceptibility via Clinical and Laboratory Standards Institute (CLSI) broth microdilution, applying CLSI epidemiological cutoff values.
Main Results:
- Isavuconazole showed potent activity against Aspergillus sections Flavi, Terrei, Nidulantes, Versicolores, and Circumdati (MIC50/90 ≤ 1 mg/L).
- Elevated minimum inhibitory concentration (MIC) values for isavuconazole and other triazoles were observed in isolates from Aspergillus sections Fumigati, Nigri, and Usti.
- Isavuconazole was active against A. parasiticus, A. tamarii, A. nomius, A. nidulans, A. unguis, A. terreus, A. alabamensis, and A. hortai, but less so against cryptic Fumigati section isolates.
Conclusions:
- Isavuconazole exhibits potent in vitro activity against a broad range of non-AFM Aspergillus species.
- Significant variability in triazole susceptibility exists among and within cryptic Aspergillus species, necessitating species-specific susceptibility testing.
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