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. 2021 Jun 19;7(6):491.
doi: 10.3390/jof7060491.

Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study: Epidemiologic Changes in a 15-Year Perspective

Malene Risum  1 , Karen Astvad  1 , Helle Krogh Johansen  2   3 , Henrik Carl Schønheyder  4   5 , Flemming Rosenvinge  6 , Jenny Dahl Knudsen  2   7 , Rasmus Krøger Hare  1 , Raluca Datcu  1 , Bent Løwe Røder  8 , Valeria Stanislavovna Antsupova  9 , Lise Kristensen  10 , Jan Berg Gertsen  10 , Jens Kjølseth Møller  11 , Esad Dzajic  12 , Turid Snekloth Søndergaard  13 , Maiken Cavling Arendrup  1   2   3
Affiliations

Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study: Epidemiologic Changes in a 15-Year Perspective

Malene Risum et al. J Fungi (Basel). .

Abstract

As part of a national surveillance programme initiated in 2004, fungal blood isolates from 2016-2018 underwent species identification and EUCAST susceptibility testing. The epidemiology was described and compared to data from previous years. In 2016-2018, 1454 unique isolates were included. The fungaemia rate was 8.13/100,000 inhabitants compared to 8.64, 9.03, and 8.38 in 2004-2007, 2008-2011, and 2012-2015, respectively. Half of the cases (52.8%) involved patients 60-79 years old and the incidence was highest in males ≥70 years old. Candida albicans accounted for 42.1% of all isolates and Candida glabrata for 32.1%. C. albicans was more frequent in males (p = 0.03) and C. glabrata in females (p = 0.03). During the four periods, the proportion of C. albicans decreased (p < 0.001), and C. glabrata increased (p < 0.001). Consequently, fluconazole susceptibility gradually decreased from 68.5% to 59.0% (p < 0.001). Acquired fluconazole resistance was found in 4.6% Candida isolates in 2016-2018. Acquired echinocandin resistance increased during the four periods 0.0%, 0.6%, 1.7% to 1.5% (p < 0.0001). Sixteen echinocandin-resistant isolates from 2016-2018 harboured well-known FKS resistance-mutations and one echinocandin-resistant C. albicans had an FKS mutation outside the hotspot (P1354P/S) of unknown importance. In C. glabrata specifically, echinocandin resistance was detected in 12/460 (2.6%) in 2016-2018 whereas multidrug-class resistance was rare (1/460 isolates (0.2%)). Since the increase in incidence during 2004-2011, the incidence has stabilised. In contrast, the species distribution has changed gradually over the 15 years, with increased C. glabrata at the expense of C. albicans. The consequent decreased fluconazole susceptibility and the emergence of acquired echinocandin resistance complicates the management of fungaemia and calls for antifungal drug development.

Keywords: Candida; candidaemia; candidiasis; echinocandin; epidemiology; mutation; resistance.

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Conflict of interest statement

Outside the study the authors declare the following potential conflicts of interest: M.R.: has over the past 5 years received research grants and travel grants from Gilead. K.A.: has, over the past 5 years, received a personal speaker fee from Pfizer and travel grants from Pfizer and Gilead. H.K.J., H.C.S., F.R., J.D.K., R.D., B.L.R., V.S.A., L.K., J.K.M., E.D., T.S.: No conflicts of interest. R.K.H.: has over the past 5 years received unrestricted research grants and travel grants from Gilead. J.B.G.: has over the past 5 years received a personal speaker fee from MSD and Gilead and travel grants from Gilead and Roche. M.C.A.: has, over the past 5 years, received research grants/contract work (paid to the SSI) from Amplyx, Basilea, Cidara, F2G, Gilead, Novabiotics, Scynexis and T2Biosystems and speaker honoraria (personal fee) from Astellas, Chiesi, Gilead, MSD, and SEGES. She is the current chairman of the EUCAST-AFST.

Figures

Figure 1
Figure 1
Number of isolates according to age and gender in 2016 to 2018.
Figure 2
Figure 2
Fungaemia species distribution and incidence per 100,000 inhabitants in 2004 to 2018. * The term non-C. albicans was used from 2004 to 2009.
Figure 3
Figure 3
Age- and gender-specific episode rates in 2016–2018 (bars) and age-specific incidences each year (lines). Incidences are determined based on the number of episodes per inhabitants in the specific age and gender groups. Population data for the age group 90+ are based on the number of inhabitants from 90 years up to 109 years old. The p-values are stated when statistically significant between genders in the specific age group.
Figure 4
Figure 4
Species distribution in proportions (%) among age groups (years) in the four periods 2004 to 2007 (A), 2008 to 2011 (B), 2012 to 2015 (C), and 2016 to 2018 (D). Number of total number of isolates within one age group is stated. Data from 2004 to 2015 have previously been published by Astvad et al. [10].
Figure 5
Figure 5
Annual consumption of selected antifungal compounds ((A) Echinocandins, (B) Fluconazole, (C) Amphotericin B, (D) voriconazole) shown in DDDs per 1000 inhabitants per year in 2004 to 2018. For Denmark the usage is divided into hospital use (Hosp) and general practitioner use (GP). Data from 2004 to 2015 were also shown in the surveillance by Astvad et al. [10].
See this image and copyright information in PMC

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