DÄ internationalArchive27-28/2023Rise in Candida Auris Cases and First Nosocomial Transmissions in Germany

Research letter

Rise in Candida Auris Cases and First Nosocomial Transmissions in Germany

Dtsch Arztebl Int 2023; 120: 477-8. DOI: 10.3238/arztebl.m2023.0047

Aldejohann, A M; Martin, R; Hecht, J; Haller, S; Rickerts, V; Walther, G; Eckmanns, T; Kurzai, O

LNSLNS

Unlike other Candida species, the species Candida auris, first described in 2009, can be transmitted efficiently via direct and indirect contact and cause nosocomial outbreaks that are difficult to control. The potential of the pathogen to develop resistance to all available classes of antimycotics makes treatment of C. auris significantly more challenging (1). Globally, more than 80% of all isolates are resistant to fluconazole, while some isolates show increased minimal inhibitory concentrations (MICs) for newer azoles. In about 10% to 30% of all isolates, the in vitro susceptibility to amphotericin B is found reduced. In addition, echinocandin resistance, resulting from a mutation in the target enzyme of this substance class (beta-1,3-D-glucan synthase), has been detected repeatedly (1).

In their most recent report on antibiotic resistance, the US Centers for Disease Control (CDC) classified C. auris as an urgent threat—the highest category. The World Health Organization (WHO) also ranks C. auris in the highest prioritization category.

The aim of this study is to describe the current epidemiological situation in Germany against the backdrop of rising case numbers in Europa (2, 3). We therefore compared data of known cases at the German National Reference Center for Invasive Fungal Infections (NRZMyk, Nationales Referenzzentrum für Invasive Pilzinfektionen) with the database of the German Antibiotic Resistance Surveillance System (ARS) Network (NET) of the Robert Koch Institute (RKI).

Methods

On the basis of isolates voluntarily submitted from primary laboratories, NRZMyk monitors the occurrence of C. auris in Germany. In addition, cases with C. auris are recorded in the antibiotic resistance surveillance (www.ars.rki.de) database of the RKI, a laboratory surveillance based on voluntary participation to continuously collect data from routine diagnostic testing.

For our analysis, we compiled and evaluated the C. auris detection data recorded until 31 November 2022 at NRZMyk and in the ARS. Resistance testing was performed using European Committee on Antimicrobial Susceptibility Testing (EUCAST)-compliant microdilution. Hot spot regions on the FKS1 gene were amplified using polymerase chain reaction (PCR) and subsequently sequenced.

Results

A total of 43 cases with C. auris were documented in the two analyzed databases ARS and NRZMyk, of these 31 only in NRZMyk and 4 only in ARS. Meaningful clinical information was available for 35 cases. Colonization was identified in 19 cases and infection in need of treatment in 16 cases (including 5 bloodstream infections). In 8 cases, the available information was insufficient to assess the clinical relevance of the detection with certainty. In 18 cases, it was known that the person had stayed abroad just prior to the detection of C. auris.

Of the 43 cases, a total of 35 initial C. auris isolates were available at NRZMyk. 80% of the tested isolates (28/35) showed a minimal inhibitory concentration (MIC) ≥ 32 µg/mL (interpretation: highly resistant). In one isolate, it was possible to demonstrate by means of molecular biological testing that echinocandin resistance was caused by a mutation in the FKS1 gene (S639Y). All strains tested had MICs for amphotericin B of 0.5–2 µg/mL. Based on these data, clinically relevant infections can usually be treated with echinocandins. At present, resistance to this class of antifungals is very rare. Alternative treatment options include newer azoles or liposomal amphotericin B. As a general rule, fluconazole should not be used therapeutically (Box).

Clinician‘s Guide: Candida auris
Box
Clinician‘s Guide: Candida auris

In 2021, the first nosocomial transmission of C. auris in a German hospital was detected (4). Our data analysis identified two further likely nosocomial transmissions (2021: 2 C. auris cases from the same medical practice, C. auris isolates genetically closely related according to NRZMyk analyses; in 2022: 2 C. auris cases from the same hospital, C. auris isolates genetically closely related according to NRZMyk analyses).

Discussion

While the absolute number of C. auris cases in Germany remains low, a significant increase in the number of detected cases of C. auris has been observed since 2020 (Figure). The same trend is also evident at the European level (3). While cases were initially sporadic and usually associated with a stay abroad, only 6 of 24 cases from 2021/2022 had a positive travel history. Furthermore, starting in 2021, the first transmission events were documented in Germany.

Candida auris cases in Germany
Figure
Candida auris cases in Germany

According to the results of interlaboratory comparisons, the vast majority of microbiological laboratories in Germany can now reliably identify the pathogen (5). Identification of C. auris is to be understood as an alarm signal and should by itself prompt the hospital to immediately initiate appropriate infection control and prevention measures (Box), for example on the basis of the currently published recommendations of the NRZMyk and the National Reference Center for the Surveillance of Nosocomial Infections (5).

Our simultaneous analysis of data from NRZMyk and ARS shows patchy coverage of C. auris cases in both systems. It can therefore be assumed that the data presented here do not cover all cases (underreporting). Given rising numbers of C. auris cases in Germany (and across Europe) and evidence of the first nosocomial transmissions of C. auris in Germany, there is a need for action (3, 4, 5). Further information and education campaigns may help raise awareness of colonization or infection with C. auris. A mandatory systematic surveillance could improve the analysis of the epidemiology of C. auris and timely, targeted intervention in case of transmission events.

Alexander M. Aldejohann, Ronny Martin, Jane Hecht, Sebastian Haller, Volker Rickerts, Grit Walther, Tim Eckmanns, Oliver Kurzai

Conflict of interest statement
AMA received fees for continuing medical education events and reimbursement of travel expenses from Gilead, Pfizer, DTG, and Junge DGHM.

GW received study support (provision of chemicals) from Pfizer, MSD and Basilea.

OK received financial support from the EU, DFG, BMBF, Else Kröner-Fresenius Stiftung, and from the Free State of Bavaria. He received lecture fees from BioMerieux, Fujifilm WAKO, Pfizer, and Gilead. Furthermore, he is a member of the Advisory Board of Mundipharma, on the board of DMykG e. V., in NAK, in the EUCAST-Antifugal Susceptibility Testing Subcommittee, and in the German Society For Hygiene And Microbiology (DGHM). He received study support from Pfizer, Gilead, F2G, Fujifilm WAKO, Mast Diagnostika, MSD, Mundipharma, Virotech, and Basilea.

The remaining authors declare that no conflict of interest exists.

Manuscript received on 18 November 2022, revised version accepted on 9 February 2023.

Cite this as:
Aldejohann AM, Martin R, Hecht J, Haller S, Rickerts V, Walther G, Eckmanns T, Kurzai O: Rise in Candida auris cases and first nosocomial transmissions in Germany. Dtsch Arztebl Int 2023; 120: 477–8. DOI: 10.3238/arztebl.m2023.0047

1.
Desoubeaux G, Coste AT, Imbert C, Hennequin C: Overview about Candida auris: What‘s up 12 years after its first description? J Mycol Med 2022; 32: 101248 CrossRef MEDLINE
2.
Plachouras D, Lötsch F, Kohlenberg A, Monnet DL, Candida auris survey collaborative group: Candida auris: epidemiological situation, laboratory capacity and preparedness in the European Union and European Economic Area*, January 2018 to May 2019. Euro Surveill 2020; 25: 2000240 CrossRef MEDLINE
3.
Kohlenberg A, Monnet DL, Plachouras D, Candida auris survey collaborative group: Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021. Euro Surveill 2022; 27: 2200846 CrossRef MEDLINE PubMed Central
4.
Hinrichs C, Wiese-Posselt M, Graf B, et al.: Successful control of Candida auris transmission in a German COVID-19 intensive care unit. Mycoses 2022; 65: 643–9 CrossRef MEDLINE PubMed Central
5.
Aldejohann AM, Wiese-Posselt M, Gastmeier P, Kurzai O: Expert recommendations for prevention and management of Candida auris transmission. Mycoses 2022; 65: 590–8 CrossRef MEDLINE
German National Reference Center for Invasive Fungal Infections (NRZMyk, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany (Walther, Kurzai) okurzai@hygiene.uni-wuerzburg.de
Institute of Hygiene and Microbiology (IHM), Julius-Maximilians University Würzburg, Würzburg, Germany (Aldejohann, Martin, Kurzai)
Robert Koch Institute, Berlin, Germany (Hecht, Haller, Rickerts, Eckmanns)
Funding
The NRZMyk is supported by the Robert Koch Institute via funds from the German Federal Ministry of Health (application number: 1369–240).
Clinician‘s Guide: Candida auris
Box
Clinician‘s Guide: Candida auris
Candida auris cases in Germany
Figure
Candida auris cases in Germany
1.Desoubeaux G, Coste AT, Imbert C, Hennequin C: Overview about Candida auris: What‘s up 12 years after its first description? J Mycol Med 2022; 32: 101248 CrossRef MEDLINE
2.Plachouras D, Lötsch F, Kohlenberg A, Monnet DL, Candida auris survey collaborative group: Candida auris: epidemiological situation, laboratory capacity and preparedness in the European Union and European Economic Area*, January 2018 to May 2019. Euro Surveill 2020; 25: 2000240 CrossRef MEDLINE
3.Kohlenberg A, Monnet DL, Plachouras D, Candida auris survey collaborative group: Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021. Euro Surveill 2022; 27: 2200846 CrossRef MEDLINE PubMed Central
4.Hinrichs C, Wiese-Posselt M, Graf B, et al.: Successful control of Candida auris transmission in a German COVID-19 intensive care unit. Mycoses 2022; 65: 643–9 CrossRef MEDLINE PubMed Central
5.Aldejohann AM, Wiese-Posselt M, Gastmeier P, Kurzai O: Expert recommendations for prevention and management of Candida auris transmission. Mycoses 2022; 65: 590–8 CrossRef MEDLINE