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Volume 25, Number 9—September 2019
Research Letter

Candida auris in Germany and Previous Exposure to Foreign Healthcare

Axel Hamprecht, Amelia E. Barber, Sibylle C. Mellinghoff, Philipp Thelen, Grit Walther, Yanying Yu, Priya Neurgaonkar, Thomas Dandekar, Oliver A. Cornely, Ronny Martin, Oliver KurzaiComments to Author , and on behalf of the German Candida auris Study Group
Author affiliations: German Centre for Infection Research, Cologne, Germany (A. Hamprecht, S.C. Mellinghoff, O.A. Cornely); University of Cologne, Cologne (A. Hamprecht, O.A. Cornely); Leibniz Institute for Natural Product Research and Infection Biology–Hans-Knoell-Institute, Jena, Germany (A.E. Barber, G. Walther, O. Kurzai); University Hospital Cologne, Cologne (S.C. Mellinghoff, P. Thelen); University of Würzburg, Würzburg, Germany (Y. Yu, P. Neurgaonkar, T. Dandekar, R. Martin, O. Kurzai)

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Abstract

The emerging yeast Candida auris has disseminated worldwide. We report on 7 cases identified in Germany during 2015–2017. In 6 of these cases, C. auris was isolated from patients previously hospitalized abroad. Whole-genome sequencing and epidemiologic analyses revealed that all patients in Germany were infected with different strains.

Candida auris is an emerging yeast that was initially described in 2009 after a case of otitis externa in Japan (1). Since then, healthcare-associated infections have been reported worldwide (2). C. auris has caused outbreaks in hospitals in Asia, Africa, and Latin America (24). In Europe, 620 C. auris cases were observed during 2013–2017 (24% infections, 76% colonizations), including 7 cases in Germany (5). Most C. auris isolates exhibit resistance to fluconazole, and susceptibility to other azoles, amphotericin B, and echinocandins varies among isolates. Some strains show resistance to all 3 classes of antifungal drugs (6).

We report on the occurrence of C. auris in Germany and its link to prior healthcare exposure in the Middle East, Asia, Africa, or the United States. C. auris was isolated from 7 patients (4 male, 3 female, all in different, unrelated hospitals) during November 2015–December 2017 (Appendix Table). Six of the patients had previously been treated in healthcare centers outside Germany and were transferred to Germany for further treatment. No further suspicious cases or isolates were reported to the National Reference Centre for Fungal Infections (Jena, Germany); however, reporting is not mandatory, and the possibility of missed cases cannot be excluded.

Of the 7 patients, 3 had been in isolation before detection of C. auris as a result of known colonization with carbapenemase-producing Enterobacteriaceae. No secondary C. auris cases were detected in any of the hospitals until March 2019. However, because no contact screening was performed, transmission resulting in asymptomatic carriage cannot be excluded.

Isolates from 6 patients were available for further testing. Biochemical identification of isolates by API ID 32C resulted in misidentification as C. sake (5 of 6) or C. intermedia (1 of 6). In contrast to previous versions, Vitek 2 version 08.01 (bioMérieux, https://www.biomerieux-diagnostics.com) identified all isolates as C. auris with 93%–99% likelihood. With VitekMS (bioMérieux) matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, no identification was achieved. However, a recent database update for VitekMS (version 3.2), which was not available at the time of our testing, corrected the identification failure in the VitekMS (data not shown). The Bruker Biotyper system (https://www.bruker.com) correctly identified all strains, albeit some with a low score (1.6–1.99). Whereas Bruker recommends that a score of 2.0 be used for species identification, a score >1.7 has been shown to be sufficient for reliable species identification (7). At the time of testing, Bruker’s research-use-only library did not include a C. auris strain of the South Asian clade, which most of the German isolates belong to. Because C. auris exhibits considerable heterogeneity of mass spectra between geographic clusters, this missing clade likely explains the low scores (8).

Figure

Thumbnail of Genetic relationships of Candida auris isolates based on whole-genome sequencing SNP analysis. A) Maximum-likelihood phylogeny of C. auris isolates from Germany (indicated by NRZ prefix) inferred to reveal a possible geographic origin. The isolates were contrasted against strains representing the 4 different clades of C. auris: South American (strain B114243 from Venezuela), East Asian (B11220 from Japan), South African (B11221 from South Africa), and South Asian (B8441 from Pakista

Figure. Genetic relationships of Candida auris isolates based on whole-genome sequencing SNP analysis. A) Maximum-likelihood phylogeny of C. auris isolates from Germany (indicated by NRZ prefix) inferred to reveal a possible geographic...

Molecular identification using internal transcribed spacer technology identified all C. auris strains with 100% identity to the reference strain DSM 21092/CBS 10913. For available isolates, we performed whole-genome sequencing and aligned reads to the B8441 v2 reference genome (Figure; Appendix). A phylogenetic tree generated from whole-genome single-nucleotide polymorphism (SNP) data indicated that the isolates NRZ-2015-214, NRZ-2017-288, NRZ-2017-367, NRZ-2017-394/1-2, and NRZ-2017-505 belong to the South Asian clade, whereas NRZ-2018-545 was related to the African clade (Figure). In line with previous studies, the genetic differences observed between isolates of the same clade were small (30–800 SNPs), whereas differences between clades were large (36,000–147,000 SNPs) (4,9). Whole-genome data show that all cases identified in Germany harbor unique isolates, thus excluding transmission between these patients (Figure). As a control, the clonality of serial isolates NRZ-2017-394/1 and NRZ-2017-394/2, taken from the same patient on 2 different occasions, was confirmed; the 2 isolates were separated by only a single SNP (Figure).

MICs of fluconazole were high for all isolates (>64 mg/L), wheareas the MICs for other antifungals were variable (Appendix Table). With the exception of NRZ-2017-545, all isolates carried either the Y132F or the K143R mutations in the ERG11 gene. However, although these mutations are linked to azole resistance, they did not result in elevated MICs for all azoles in these isolates (Appendix Table) (10). We identified a S639Y mutation in the FKS1 hotspot 1 of isolate NRZ-2017-505, which was highly resistant to anidulafungin (MIC 16 mg/L).

In conclusion, C. auris has so far been isolated from individual cases in Germany. Most of these cases (6 of 7) occurred in patients who had previously been hospitalized abroad and were admitted to hospitals in Germany for continuation of medical treatment. No information on contact or environmental screening was available; such screening was likely not performed in most institutions. Thus, silent transmission and resulting carriage may have occurred unnoticed. However, no secondary cases were detected in any of the 7 hospitals affected.

Dr. Hamprecht is a clinical microbiologist at the Institute for Medical Microbiology, Immunology and Hygiene and professor for antibiotic resistance of gram-negative pathogens at the University of Cologne, Germany, and the German Centre for Infection Research (DZIF), also in Cologne. His research interests include multidrug-resistant organisms (mainly Enterobacterales and fungi), their resistance mechanisms, and the improvement of diagnostic methods.

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Acknowledgment

Members of the German Candida auris Study Group: Gerhard Haase (Labordiagnostisches Zentrum, Universitätsklinikum RWTH Aachen, Aachen, Germany); Jette Jung (Max von Pettenkofer-Institut, Munich, Germany); Heike Freidank (Städtisches Klinikum München GmbH, Munich); Michaela Simon (Institut für Med. Mikrobiologie und Hygiene, Regensburg, Germany); Jörg Steinmann (Institut für Klinikhygiene, Medizinische Mikrobiologie und Klinische Infektiologie, Universitätsinstitut der Paracelsus Medizinischen Privatuniversität, Nuremberg, Germany).

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References

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Cite This Article

DOI: 10.3201/eid2509.190262

Original Publication Date: 6/12/2019

1Group members are listed at end of this article.

Table of Contents – Volume 25, Number 9—September 2019

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Oliver Kurzai, University of Würzburg Institute for Hygiene and Microbiology, Josef-Schneider-Straße 2 / E1, Würzburg 97080, Germany

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Page created: August 21, 2019
Page updated: August 21, 2019
Page reviewed: August 21, 2019
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