Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital

oleh: Lívia Maria Maciel da Fonseca, Vanessa Fávaro Braga, Ludmilla Tonani, Patrícia Helena Grizante Barião, Erika Nascimento, Roberto Martinez, Marcia Regina von Zeska Kress

Format: Article
Diterbitkan: MDPI AG 2023-11-01

Deskripsi

The genus <i>Aspergillus</i> harbors human infection-causing pathogens and is involved in the complex one-health challenge of antifungal resistance. Here, a 6-year retrospective study was conducted with <i>Aspergillus</i> spp. isolated from patients with invasive, chronic, and clinically suspected aspergillosis in a tertiary teaching hospital. A total of 64 <i>Aspergillus</i> spp. clinical isolates were investigated regarding molecular identification, biofilm, virulence in <i>Galleria mellonella</i>, antifungal susceptibility, and resistance to amphotericin B and azoles. <i>Aspergillus</i> section <i>Fumigati</i> (<i>A. fumigatus sensu stricto</i>, 62.5%) and section <i>Flavi</i> (<i>A. flavus</i>, 20.3%; <i>A. parasiticus</i>, 14%; and <i>A. tamarii</i>, 3.1%) have been identified. <i>Aspergillus</i> section <i>Flavi</i> clinical isolates were more virulent than section <i>Fumigati</i> clinical isolates. Furthermore, scant evidence supports a link between biofilm formation and virulence. The susceptibility of the <i>Aspergillus</i> spp. clinical isolates to itraconazole, posaconazole, voriconazole, and amphotericin B was evaluated. Most <i>Aspergillus</i> spp. clinical isolates (67.2%) had an AMB MIC value equal to or above 2 µg/mL, warning of a higher probability of therapeutic failure in the region under study. In general, the triazoles presented MIC values above the epidemiological cutoff value. The high triazole MIC values of <i>A. fumigatus s.s.</i> clinical isolates were investigated by sequencing the promoter region and <i>cyp51A</i> locus. The Cyp51A amino acid substitutions F46Y, M172V, N248T, N248K, D255E, and E427K were globally detected in 47.5% of <i>A. fumigatus s.s.</i> clinical isolates, and most of them are associated with high triazole MICs. Even so, the findings support voriconazole or itraconazole as the first therapeutic choice for treating <i>Aspergillus</i> infections. This study emphasizes the significance of continued surveillance of <i>Aspergillus</i> spp. infections to help overcome the gap in knowledge of the global fungal burden of infections and antifungal resistance, supporting public health initiatives.