Affiliation:
1. JMI Laboratories, North Liberty, Iowa, USA
2. University of Iowa, Iowa City, Iowa, USA
Abstract
ABSTRACT
Azole resistance in
Aspergillus fumigatus
(AFM) is increasing and often associated with
cyp51
alterations. We evaluated the activity of isavuconazole and other mold-active azoles against 731 AFM isolates causing invasive aspergillosis collected in Europe (EU;
n
= 449) and North America (NA;
n
= 282). Isolates were submitted to CLSI susceptibility testing and epidemiological cutoff value (ECV) criteria. A posaconazole ECV of 0.5 mg/L was used as no CLSI ECV was determined. Azole non-wild-type (NWT) isolates were submitted for
cyp51
sequencing by whole genome sequencing. Overall, isavuconazole activity (92.7%/94.0% WT in EU/NA) was comparable to other azoles (WT rate range, 90.9%–96.4%/91.8%–98.6%, respectively), regardless of the region. A total of 79 (10.8%) azole NWT isolates were detected, and similar rates of these isolates were noted in EU (10.7%) and NA (11.0%). Although most AFM were WT to azoles, increasing azole NWT rates were observed in NA (from 6.0% in 2017 to 29.3% in 2021). Azole NWT rates varied from 4.9% (2019) to 20.6% (2018) in EU without an observed trend.
cyp51
alterations occurred in 56.3%/54.8% of azole NWT from EU/NA, respectively. The
cyp51A
TR
34
/L98H alteration was observed only in EU isolates (72.0% of EU isolates), while
cyp51A
I242V occurred only in NA isolates (58.3%). Isavuconazole remained active (MIC, ≤1 mg/L) against 18.5/47.1% of azole NWT AFM exhibiting
cyp51
alterations in EU/NA, along with voriconazole (29.6/82.4%; MIC, ≤1 mg/L) and posaconazole (48.1/88.2%; MIC, ≤0.5 mg/L). Fourteen different
cyp51
alterations were detected in 44 of 79 NWT isolates. The
in vitro
activity of the azoles varied in AFM that displayed
cyp51
alterations.
IMPORTANCE
A few microbiology laboratories perform antifungal susceptibility testing locally for systemically active antifungal agents. The identification of emerging azole-resistant
Aspergillus fumigatus
is worrisome. As such, there is a critical role for antifungal surveillance in tracking emerging resistance among both common and uncommon opportunistic fungi. Differences in the regional prevalence and antifungal resistance of these fungi render local epidemiological knowledge essential for the care of patients with a suspected invasive fungal infection.
Publisher
American Society for Microbiology