PMID- 35412354 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20221013 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 66 IP - 5 DP - 2022 May 17 TI - Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations. PG - e0172521 LID - 10.1128/aac.01725-21 [doi] LID - e01725-21 AB - Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC >/= 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method. FAU - Desnos-Ollivier, Marie AU - Desnos-Ollivier M AUID- ORCID: 0000-0002-9137-0466 AD - Institut Pasteurgrid.428999.7, Universite de Paris, CNRS UMR2000, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, Paris, France. FAU - Bretagne, Stephane AU - Bretagne S AD - Institut Pasteurgrid.428999.7, Universite de Paris, CNRS UMR2000, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, Paris, France. AD - Universite de Paris, Laboratoire de Parasitologie-Mycologie, Hopital Saint Louis, AP-HP, Paris, France. FAU - Lortholary, Olivier AU - Lortholary O AD - Institut Pasteurgrid.428999.7, Universite de Paris, CNRS UMR2000, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, Paris, France. AD - Service des Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Hopital Necker-Enfants malades, APHP, IHU Imagine, Paris, France. AD - Universite de Paris, Paris, France. FAU - Dromer, Francoise AU - Dromer F AUID- ORCID: 0000-0003-1671-1475 AD - Institut Pasteurgrid.428999.7, Universite de Paris, CNRS UMR2000, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, Paris, France. CN - French Mycoses Study Group N. Brieu CH Aix, T. Chouaki , C. Damiani , A. Totet CHU Amiens, J. P. Bouchara , D. Chabasse , M. Pihet CHU Angers, S. Bland CH Annecy, V. Blanc CH Antibes, S. Branger CH Avignon, A. P. Bellanger , L. Millon CHU Besancon, C. Plassart CH Beauvais, I. Poilane Hopital Jean Verdier, Bondy, I. Accoceberry , L. Delhaes , B. Couprie , F. Gabriel CH Bordeaux, J. Dunand , A. L. Roux , V. Sivadon-Tardy Hopital Ambroise Pare, Boulogne Billancourt, F. Laurent CH, Bourg en Bresse, S. Legal , E. Moalic , G. Nevez , D. Quinio CHU Brest, M. Cariou CH Bretagne Sud, J. Bonhomme , C. Duhamel CHU, Caen, B. Podac CH, Chalon sur Saone, S. Lechatch CH, Charleville-Mezieres, C. Soler Hopital d'Instruction des armees, Clamart, M. Cambon , C. Nourrisson , P. Poirier , D. Pons CHU, Clermont Ferrand, O. Augereau , I. Grawey CH, Colmar, N. Fauchet CHIC, Creteil, A. Bonnin , F. Dalle CHU, Dijon, P. Cahen , P. Honderlick CMC, Foch, N. Desbois , C. Miossec CHU, Fort de France, J. L. Hermann Hopital Raymond Poincare, Garches, M. Cornet , R. Grillot , B. Lebeau , D. Maubon , H. Pelloux CHU, Grenoble, M. Nicolas CHU, Guadeloupe, C. Aznar , D. Blanchet , J. F. Carod , M. Demar CHU, Guyane, A. Angoulvant Hopital Bicetre, le Kremlin Bicetre, C. Ciupek CH, Le Mans, A. Gigandon Hopital Marie Lannelongue, Le Plessis Robinson, B. Bouteille CH Limoges, E. Frealle , D. Poulain , B. Sendid CHU Lille, D. Dupont , J. Menotti , F. Persat , M.-A. Piens , M. Wallon CHU, Lyon, C. Cassagne , S. Ranque CHU, Marseille, T. Benoit-Cattin , L. Collet CH Mayotte, A. Fiacre CH Meaux, N. Bourgeois , L. Lachaud , P. Rispail , Y. Sterkers CHU, Montpellier, M. Machouart CHU, Nancy, F. Gay-Andrieu , P. Lepape , F. Morio CHU, Nantes, O. Moquet CH, Nevers, S. Lefrancois Hopital Americain, Neuilly, M. Sasso CHU, Nimes, F. Reibel GH, Nord-Essone, M. Gari-Toussaint , L. Hasseine CHU Nice, L. Bret , D. Poisson CHR Orleans, S. Brun Hopital Avicenne, Paris, C. Bonnal , C. Chochillon , S. Houze Hopital Bichat, Paris, A. Paugam Hopital Cochin, Paris, N. Ait-Ammar , F. Botterel , R. Chouk CHU Henri Mondor, Paris, M. E. Bougnoux , E. Sitterle Hopital Necker, Paris, A. Fekkar , R. Piarroux Hopital Pitie Salpetriere, Paris, J. Guitard , C. Hennequin , J.-L. Poirot Hopital St Antoine, Paris, M. Gits-Muselli , S. Hamane , C. Lacroix Hopital Saint Louis, Paris, S. Bonacorsi , P. Mariani Hopital Robert Debre, Paris, D. Moissenet Hopital Trousseau, Paris, C. Kauffmann-Lacroix , A. Minoza , E. Perraud , M. H. Rodier CHU Poitiers, G. Colonna CH, Porto Vecchio, A. Huguenin , D. Toubas CHU Reims, S. Chevrier , J. P. Gangneux , F. Robert-Gangneux , C. Guigen CHU Rennes, O. Belmonte , G. Hoarau , M. C. Jaffar Bandjee , J. Jaubert , S. Picot , N. Traversier CHU Reunion, L. Favennec , G. Gargala CHU, Rouen, N. Godineau , C. Tournus CH, St Denis, C. Mahinc , H. Raberin CHU, St Etienne, V. Letscher Bru CHU, Strasbourg, S. Cassaing CHU, Toulouse, P. Patoz CH Tourcoing, E. Bailly , J. Chandenier , G. Desoubeaux CHU Tours, F. Moreau CH Troyes, P. Munier CH Valence, E. Mazars CH Valenciennes, O. Eloy CH Versailles, E. Chachaty Institut Gustave Roussy, Villejuif LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20220412 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Antifungal Agents) RN - 0 (Echinocandins) RN - 0 (Lipopeptides) RN - 9HLM53094I (Anidulafungin) RN - F0XDI6ZL63 (Caspofungin) RN - R10H71BSWG (Micafungin) SB - IM MH - Anidulafungin/pharmacology/therapeutic use MH - Antifungal Agents/pharmacology/therapeutic use MH - *Candidiasis, Invasive/drug therapy MH - Caspofungin/pharmacology/therapeutic use MH - Drug Resistance, Fungal/genetics MH - *Echinocandins/therapeutic use MH - Humans MH - Lipopeptides/pharmacology/therapeutic use MH - Micafungin/pharmacology/therapeutic use MH - Microbial Sensitivity Tests MH - Mutation PMC - PMC9116480 OTO - NOTNLM OT - FKS mutation OT - MIC distribution OT - anidulafungin OT - antifungal resistance OT - caspofungin OT - common yeast OT - micafungin OT - rare yeast OT - yeasts COIS- The authors declare no conflict of interest. EDAT- 2022/04/13 06:00 MHDA- 2022/05/20 06:00 PMCR- 2022/10/12 CRDT- 2022/04/12 12:11 PHST- 2022/04/13 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2022/04/12 12:11 [entrez] PHST- 2022/10/12 00:00 [pmc-release] AID - 01725-21 [pii] AID - aac.01725-21 [pii] AID - 10.1128/aac.01725-21 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2022 May 17;66(5):e0172521. doi: 10.1128/aac.01725-21. Epub 2022 Apr 12.