Azole resistance in Aspergillus fumigatus. The first 2-year's Data from the Danish National Surveillance Study, 2018-2020

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 TR(34)/L98H prevalence was 3.6% (39/1083) and included the variants TR(34)/L98H, TR(34) (3)/L98H and TR(34)/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, TR(34)/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 TR(34)/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

Diagnostic Issues, Clinical Characteristics, and Outcomes for Patients with Fungemia▿

This study investigated microbiological, clinical, and management issues and outcomes for Danish fungemia patients. Isolates and clinical information were collected at six centers. A total of 334 isolates, 316 episodes, and 305 patients were included, corresponding to 2/3 of the national episodes. Blood culture positivity varied by system, species, and procedure. Thus, cases with concomitant bacteremia were reported less commonly by BacT/Alert than by the Bactec system (9% [11/124 cases] versus 28% [53/192 cases]; P < 0.0001), and cultures with Candida glabrata or those drawn via arterial lines needed longer incubation. Species distribution varied by age, prior antifungal treatment (57% occurrence of C. glabrata, Saccharomyces cerevisiae, or C. krusei in patients with prior antifungal treatment versus 28% occurrence in those without it; P = 0.007), and clinical specialty (61% occurrence of C. glabrata or C. krusei in hematology wards versus 27% occurrence in other wards; P = 0.002). Colonization samples were not predictive for the invasive species in 11/100 cases. Fifty-six percent of the patients had undergone surgery, 51% were intensive care unit (ICU) patients, and 33% had malignant disease. Mortality increased by age (P = 0.009) and varied by species (36% for C. krusei, 25% for C. parapsilosis, and 14% for other Candida species), severity of underlying disease (47% for ICU patients versus 24% for others; P = 0.0001), and choice but not timing of initial therapy (12% versus 48% for patients with C. glabrata infection receiving caspofungin versus fluconazole; P = 0.023). The initial antifungal agent was deemed suboptimal upon species identification in 15% of the cases, which would have been 6.5% if current guidelines had been followed. A large proportion of Danish fungemia patients were severely ill and received suboptimal initial antifungal treatment. Optimization of diagnosis and therapy is possible