Accuracy of Sensititre YeastOne echinocandins epidemiological cut-off values for identification of FKS mutant Candida albicans and Candida glabrata: a ten year national survey of the Fungal Infection Network of Switzerland (FUNGINOS)

A Kritikos; D Neofytos; N Khanna; P W Schreiber; K Boggian; J Bille; J Schrenzel; K Mühlethaler; R Zbinden; T Bruderer; D Goldenberger; G Pfyffer; A Conen; C Van Delden; S Zimmerli; D Sanglard; D Bachmann; O Marchetti; F Lamoth; Fungal Infection Network of Switzerland (FUNGINOS)

doi:10.1016/j.cmi.2018.05.012

Accuracy of Sensititre YeastOne echinocandins epidemiological cut-off values for identification of FKS mutant Candida albicans and Candida glabrata: a ten year national survey of the Fungal Infection Network of Switzerland (FUNGINOS)

Clin Microbiol Infect. 2018 Nov;24(11):1214.e1-1214.e4. doi: 10.1016/j.cmi.2018.05.012. Epub 2018 Jun 15.

Authors

A Kritikos¹, D Neofytos², N Khanna³, P W Schreiber⁴, K Boggian⁵, J Bille⁶, J Schrenzel⁷, K Mühlethaler⁸, R Zbinden⁴, T Bruderer⁹, D Goldenberger¹⁰, G Pfyffer¹¹, A Conen¹², C Van Delden², S Zimmerli¹³, D Sanglard¹⁴, D Bachmann¹⁴, O Marchetti¹⁵, F Lamoth¹⁶; Fungal Infection Network of Switzerland (FUNGINOS)

Collaborators

Fungal Infection Network of Switzerland (FUNGINOS):
T Bregenzer¹⁷, A Conen¹⁸, U Flückiger¹⁹, N Khanna¹⁹, C Orasch²⁰, U Heininger²¹, M Franciolli²², L Damonti, S Zimmerli²², M Rothen²³, C Zellweger²⁴, P Tarr²⁵, F Fleisch²⁶, C Chuard²⁷, V Erard²⁸, S Emonet²⁹, J Garbino²⁹, C van Delden²⁹, D Genne³⁰, P Bochud³¹, T Calandra³¹, F Lamoth³¹, O Marchetti³¹, J Chave³², P Graber³³, R Monotti³⁴, O Regionale³⁴, E Bernasconi³⁵, O Civico³⁵, M Rossi³⁶, M Krause³⁷, R Piso³⁸, F Bally³⁹, N Troillet³⁹, K Boggian⁴⁰, G Eich⁴¹, J Gubler⁴², J Fehr⁴³, A Imhof⁴³, C Ruef⁴³, C Berger⁴⁴, H Fankhauser¹⁷, I Heinzer¹⁷, R Frei¹⁹, R Hertel²¹, M Dolina⁴⁵, O Petrini⁴⁵, O Dubuis⁴⁶, K Mühlethaler²², S Graf⁴⁷, M Risch²⁶, E Ritzler²⁶, D Fracheboud²⁷, J Schrenzel²⁹, P Rohner²⁹, R Lienhardt³⁰, J Bille³¹, C Andreutti-Zaugg⁴⁸, A Gallusser⁴⁸, G Pfyffer³⁶, K Herzog³⁷, U Schibli³⁸, L Tissière³⁹, T Bruderer⁴⁰, D Schultze⁴⁰, R Zbinden⁴³

Affiliations

¹ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
² Service of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³ Division of Infectious Diseases and Hospital Epidemiology, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research, University Hospital of Basel, Basel, Switzerland.
⁴ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Division of Infectious Diseases and Hospital Hygiene, Cantonal Hospital, Sankt Gallen, Switzerland.
⁶ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland.
⁷ Service of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁸ Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland.
⁹ Department of Bacteriology, Mycology and Parasitology, Centre of Laboratory Medicine, Cantonal Hospital of Sankt Gallen, Sankt Gallen, Switzerland.
¹⁰ Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
¹¹ Department of Medical Microbiology, Canton Hospital of Luzern, Luzern, Switzerland.
¹² Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital of Aarau, Aarau, Switzerland.
¹³ Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹⁴ Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁵ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland.
¹⁶ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: [email protected].
¹⁷ Kantonsspital, Aarau, Switzerland.
¹⁸ Kantonsspital, Aarau, Switzerland; University Hospital, Basel, Switzerland.
¹⁹ University Hospital, Basel, Switzerland.
²⁰ University Hospital, Basel, Switzerland; University Hospital, Lausanne, Switzerland.
²¹ Universitätskinderspital, Basel, Switzerland.
²² University Hospital, Bern, Switzerland.
²³ Spitalzentrum, Biel, Switzerland; Kantonsspital, Bruderholz, Switzerland.
²⁴ Spitalzentrum, Biel, Switzerland.
²⁵ Kantonsspital, Bruderholz, Switzerland.
²⁶ Kantonsspital, Chur, Switzerland.
²⁷ Hôpital Cantonal, Fribourg, Switzerland.
²⁸ Hôpital Cantonal, Fribourg, Switzerland; Hôpital Communal, La-Chaux-de-Fonds, Switzerland.
²⁹ University Hospital, Geneva, Switzerland.
³⁰ Hôpital Communal, La-Chaux-de-Fonds, Switzerland.
³¹ University Hospital, Lausanne, Switzerland.
³² Clinique Bois-Cerf, Clinique Cécil, Switzerland; Clinique La Source, Lausanne, Switzerland.
³³ Kantonsspital, Liestal, Switzerland.
³⁴ Ente Ospedaliero Cantonale, Locarno, Switzerland.
³⁵ Ente Ospedaliero Cantonale, Lugano, Switzerland.
³⁶ Kantonsspital, Luzern, Switzerland.
³⁷ Kantonsspital, Münsterlingen, Switzerland.
³⁸ Kantonsspital, Olten, Switzerland.
³⁹ Institut Central des Hôpitaux Valaisans, Sion, Switzerland.
⁴⁰ Kantonsspital, Sankt Gallen, Switzerland.
⁴¹ Kantonsspital, Sankt Gallen, Switzerland; University Hospital, Zürich, Switzerland.
⁴² Kantonsspital, Winterthur, Switzerland; Stadtspital Triemli, Zürich, Switzerland.
⁴³ University Hospital, Zürich, Switzerland.
⁴⁴ Universitätskinderspital, Zürich, Switzerland.
⁴⁵ Istituto Cantonale di Microbiologia, Bellinzona, Switzerland.
⁴⁶ Viollier Microbiology Laboratories, Bienne, Switzerland.
⁴⁷ Kantonsspital, Bruderholz, Switzerland; Kantonsspital, Liestal, Switzerland; Kantospital, Liestal, Switzerland.
⁴⁸ Clinique La Source, Lausanne, Switzerland.

PMID: 29909005
DOI: 10.1016/j.cmi.2018.05.012

Abstract

Objectives: Echinocandins represent the first-line treatment of candidaemia. Acquired echinocandin resistance is mainly observed among Candida albicans and Candida glabrata and is associated with FKS hotspot mutations. The commercial Sensititre YeastOne™ (SYO) kit is widely used for antifungal susceptibility testing, but interpretive clinical breakpoints are not well defined. We determined echinocandins epidemiological cut-off values (ECV) for C. albicans/glabrata tested by SYO and assessed their ability to identify FKS mutants in a national survey of candidaemia.

Methods: Bloodstream isolates of C. albicans and C. glabrata were collected in 25 Swiss hospitals from 2004 to 2013 and tested by SYO. FKS hotspot sequencing was performed for isolates with an MIC≥ECV for any echinocandin.

Results: In all, 1277 C. albicans and 347 C. glabrata were included. ECV 97.5% of caspofungin, anidulafungin and micafungin were 0.12, 0.06 and 0.03 μg/mL for C. albicans, and 0.25, 0.12 and 0.03 μg/mL for C. glabrata, respectively. FKS hotspot sequencing was performed for 70 isolates. No mutation was found in the 52 'limit wild-type' isolates (MIC=ECV for at least one echinocandin). Among the 18 'non-wild-type' isolates (MIC>ECV for at least one echinocandin), FKS mutations were recovered in the only two isolates with MIC>ECV for all three echinocandins, but not in those exhibiting a 'non-wild-type' phenotype for only one or two echinocandins.

Conclusion: This 10-year nationwide survey showed that the rate of echinocandin resistance among C. albicans and C. glabrata remains low in Switzerland despite increased echinocandin use. SYO-ECV could discriminate FKS mutants from wild-type isolates tested by SYO in this population.

Keywords: Anidulafungin; Antifungal susceptibility testing; Candidaemia; Caspofungin; FKS hotspot; Micafungin; Minimal inhibitory concentration.

MeSH terms

Antifungal Agents / pharmacology*
Candida albicans / genetics*
Candida glabrata
Candidiasis / microbiology*
Drug Resistance, Fungal*
Echinocandins / administration & dosage
Echinocandins / pharmacology*
Humans
Microbial Sensitivity Tests
Mutation
Population Surveillance
Switzerland / epidemiology

Substances

Antifungal Agents
Echinocandins