Azole resistance in Aspergillus fumigatus. The first 2‐year's Data from the Danish National Surveillance Study, 2018–2020. Issue 4 (8th February 2022)

• Record Type: Journal Article
• Authors: Risum, Malene; Hare, Rasmus Krøger; Gertsen, Jan Berg; Kristensen, Lise; Rosenvinge, Flemming Schønning; Sulim, Sofia; Abou‐Chakra, Nissrine; Bangsborg, Jette; Røder, Bent Løwe; Marmolin, Ea Sofie; Astvad, Karen Marie Thyssen; Pedersen, Michael; Dzajic, Esad; Andersen, Steen Lomborg; Arendrup, Maiken Cavling
• Is Part Of: Mycoses. Volume 65:Issue 4(2022)
• Page Start: 419
• Page End: 428
• Publication Date: 2022-02-08
• Subjects: antifungal susceptibility -- Aspergillus fumigatus -- azole resistance -- environmental route -- itraconazole -- medical route -- TR34/L98H -- voriconazole; Pathogenic fungi -- Periodicals; Medical mycology -- Periodicals; 616.969
• DOI: 10.1111/myc.13426
• Languages: English
• ISSNs: 0933-7407

Abstract

Abstract: Background: Azole resistance complicates treatment of patients with invasive aspergillosis with an increased mortality. Azole resistance in Aspergillus fumigatus is a growing problem and associated with human and environmental azole use. Denmark has a considerable and highly efficient agricultural sector. Following reports on environmental azole resistance in A. fumigatus from Danish patients, the ministry of health requested a prospective national surveillance of azole‐resistant A. fumigatus and particularly that of environmental origin. Objectives: To present the data from the first 2 years of the surveillance programme. Methods: Unique isolates regarded as clinically relevant and any A. fumigatus isolated on a preferred weekday (background samples) were included. EUCAST susceptibility testing was performed and azole‐resistant isolates underwent cyp51A gene sequencing. Results: The azole resistance prevalence was 6.1% (66/1083) at patient level. The TR34 /L98H prevalence was 3.6% (39/1083) and included the variants TR34 /L98H, TR34 3 /L98H and TR34 /L98H/S297T/F495I. Resistance caused by other Cyp51A variants accounted for 1.3% (14/1083) and included G54R, P216S, F219L, G54W, M220I, M220K, M220R, G432S, G448S and Y121F alterations. Non‐Cyp51A‐mediated resistance accounted for 1.2% (13/1083). Proportionally, TR34 /L98H, other Cyp51A variants and non‐Cyp51A‐mediated resistance accounted for 59.1% (39/66), 21.2% (14/66) and 19.7% (13/66), respectively, of all resistance. Azole resistance was detected in all five regions in Denmark, and TR34 /L98H specifically, in four of five regions during the surveillance period. Conclusion: The azole resistance prevalence does not lead to a change in the initial treatment of aspergillosis at this point, but causes concern and leads to therapeutic challenges in the affected patients.