TY - JOUR A1 - Aldejohann, Alexander Maximilian A1 - Wiese-Posselt, Miriam A1 - Gastmeier, Petra A1 - Kurzai, Oliver T1 - Expert recommendations for prevention and management of Candida auris transmission JF - Mycoses N2 - Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C. auris frequently exhibits multi-drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C. auris does cause superficial and life-threatening invasive infections. During management of the first documented C. auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C. auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C. auris transmission and potential outbreak situations. Rapid and effective measures to contain C. auris spread require a multi-disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step-wise process and relevant interventions differ between management of singular C. auris colonised / infected patients and detection of potential C. auris transmission or nosocomial outbreaks. KW - Candida auris KW - nosocomial transmission KW - infection prevention KW - expert recommendation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318570 VL - 65 IS - 6 SP - 590 EP - 598 ER - TY - THES A1 - Aldejohann, Alexander Maximilian T1 - Echinocandin-Resistenzen in \(Candida\) \(glabrata\) T1 - Echinocandin resistance in \(Candida\) \(glabrata\) N2 - Candida glabrata ist die zweithäufigste Ursache von Candidämien und invasiven Hefepilzinfektionen in Europa. Im Gegensatz zu C. albicans zeigt C. glabrata eine reduzierte Empfindlichkeit gegen bestimmte Antimykotika und kann unter Therapie rasch Resistenzen entwickeln. Diese Arbeit umfasst eine systematische geno- und phänotypische Resistenzanalyse einer der größten europäischen - durch das NRZMyk in 5 Jahren zusammengetragenen - C. glabrata Stammsammlungen bestehend aus 176 klinisch relevanter Isolate. 84 der Stämme wurden anhand Referenztestung nach EUCAST zunächst als Anidulafungin (AND) resistent eingestuft. 71 wiesen konkordante Mutationen in den für die Glucan-Synthetase kodierenden FKS-Genen auf (13 % in FKS1, 87 % in FKS2). Vor allem die Position Ser-663 (FKS2-HS1) imponierte mit signifikant erhöhten AND MHK-Werten. 11 FKS-Wildtyp-Isolate, die ursprünglich als AND resistent klassifiziert wurden, wiesen in multiplen Nachtestungen um den Breakpoint undulierende AND MHK-Werte auf. 2 FKS-Wildtyp Isolate zeigten durchgängig hohe AND MHK-Werte und mussten daher - trotz fehlender Zielgenmutationen - als resistent eingestuft werden. Diese extremen Phänotypen wurden durch einen verblindeten nationalen Ringversuch bestätigt. Über ein Drittel der Isolate war multiresistent. Stämme aus Blutstrominfektionen und Ser-663 Mutation waren mit einer erhöhten Mortalität assoziiert. Ein weiteres Kernelement war die Detektion von Azol-resistenten C. glabrata petite-Phänotypen in der Routinediagnostik. Hier wurden innerhalb von 8 Monaten 20 relevante Isolate identifiziert. Die Ergebnisse belegen das regelmäßige Auftreten single- / multidrug-resistenter C. glabrata Isolate in Deutschland. Phänotypische Resistenztestungen können zu Fehlklassifizierung von sensiblen Isolaten führen. FKS-Genotypisierungen hingegen sind ein nützliches Tool zur Identifizierung relevanter Resistenzen. In seltenen Fällen scheint jedoch eine Echinocandin-Resistenz ohne genotypisches Korrelat möglich zu sein. N2 - Candida glabrata is the second most common cause of candidaemia and invasive yeast infections in Europe. In contrast to C. albicans, C. glabrata shows reduced susceptibility to certain antifungal agents and can rapidly acquire resistance under therapy. This work comprises a systematic geno- and phenotypic resistance analysis of one of the largest European C. glabrata strain collections - compiled by NRZMyk in 5 years - consisting of 176 clinically relevant isolates. 84 of the strains were initially classified as anidulafungin (AND) resistant by reference testing according to EUCAST. 71 showed concordant mutations in FKS genes encrypting the glucan synthetase (13 % in FKS1, 87 % in FKS2). In particular, the position Ser-663 (FKS2-HS1) impressed with significantly increased AND MIC-values. 11 FKS wild-type isolates, originally classified as AND resistant, showed fluctuating AND MIC-values near the clinical breakpoint after retests with multiple assays. Two FKS wild-type isolates showed consistently high AND MIC values and therefore had to be classified as resistant - despite the absence of target gene mutations. These extreme phenotypes were confirmed in a blinded national ring trial. More than one third of echinocandin-resistant isolates showed concordant fluconazole resistance. Strains from bloodstream infections and Ser-663 mutation were associated with high mortality. Another core element was the detection of azole-resistant C. glabrata petite phenotypes in routine diagnostics. Here, 20 relevant isolates were identified within 8 months, which could be assigned to 8 patients. These results demonstrate the regular occurrence of single- / multidrug-resistant C. glabrata isolates in Germany. Phenotypic resistance testing can lead to misclassification of susceptible isolates. FKS genotyping, on the other hand, is a useful tool for identifying resistant strains. However, in rare cases, echinocandin resistance without a genotypic correlate seems to be possible. KW - Resistenzbestimmung KW - Candida KW - Multidrug-Resistenz KW - Anidulafungin KW - Micafungin KW - Invasive Mykosen KW - Invasive Fungal Infections KW - C. glabrata KW - Multidrug-Resistenzen KW - Antimykotika KW - Mikrodilution KW - Anidulafungin KW - MDR KW - Susceptibility Testing KW - FKS-genes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275840 ER -