1. Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations
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Desnos-Ollivier, Marie, Bretagne, Stéphane, Lortholary, Olivier, Dromer, Françoise, French Mycoses Study Group, The, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was supported by Santé Publique France and Institut Pasteur., Members of the French Mycoses Study Group who contributed to the data are, in alphabetical order of the cities, all the French microbiologists and mycologists who sent isolates for characterization of unusual antifungal susceptibility profiles or to contribute to the ongoing surveillance program on the epidemiology of invasive fungal infections in France (YEASTS and RESSIF programs): 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 Besançon), C. Plassart (CH Beauvais), I. Poilane (Hôpital Jean Verdier, Bondy), I. Accoceberry, L. Delhaes, B. Couprie, F. Gabriel (CH Bordeaux), J. Dunand, A. L. Roux, V. Sivadon-Tardy (Hôpital Ambroise Paré, 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 Saône), S. Lechatch (CH, Charleville-Mézières), C. Soler (Hopital d’Instruction des armées, Clamart), M. Cambon, C. Nourrisson, P. Poirier, D. Pons (CHU, Clermont Ferrand), O. Augereau, I. Grawey (CH, Colmar), N. Fauchet (CHIC, Créteil), A. Bonnin, F. Dalle (CHU, Dijon), P. Cahen, P. Honderlick (CMC, Foch), N. Desbois, C. Miossec (CHU, Fort de France), J. L. Hermann (Hôpital Raymond Poincaré, 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 (Hôpital Bicêtre, le Kremlin Bicêtre), C. Ciupek (CH, Le Mans), A. Gigandon (Hôpital 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. Lefrançois (Hôpital Américain, Neuilly), M. Sasso (CHU, Nimes), F. Reibel (GH, Nord-Essone), M. Gari-Toussaint, L. Hasseine (CHU Nice), L. Bret, D. Poisson (CHR Orléans), S. Brun (Hôpital Avicenne, Paris), C. Bonnal, C. Chochillon, S. Houzé (Hôpital Bichat, Paris), A. Paugam (Hôpital Cochin, Paris), N. Ait-Ammar, F. Botterel, R. Chouk (CHU Henri Mondor, Paris), M. E. Bougnoux, E. Sitterle (Hôpital Necker, Paris), A. Fekkar, R. Piarroux (Hôpital Pitié Salpêtrière, Paris), J. Guitard, C. Hennequin, J.-L. Poirot (Hôpital St Antoine, Paris), M. Gits-Muselli, S. Hamane, C. Lacroix (Hôpital Saint Louis, Paris), S. Bonacorsi, P. Mariani (Hôpital Robert Debré, Paris), D. Moissenet (Hôpital 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 Réunion), 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), and and members of the NRCMA (Institut Pasteur, Paris): A. Bertho, C. Blanc, A. Boullié, C. Gautier, V. Geolier, D. Hoinard, and D. Raoux-Barbot for technical help, and K. Boukris-Sitbon, F. Lanternier, A. Alanio, and D. Garcia-Hermoso for their expertise and contribution to the surveillance programs.
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Pharmacology ,Antifungal Agents ,[SDV]Life Sciences [q-bio] ,yeasts ,Microbial Sensitivity Tests ,antifungal resistance ,Anidulafungin ,bacterial infections and mycoses ,rare yeast ,common yeast ,Echinocandins ,Lipopeptides ,Infectious Diseases ,Susceptibility ,Caspofungin ,Drug Resistance, Fungal ,Mutation ,Micafungin ,polycyclic compounds ,FKS mutation ,Humans ,Candidiasis, Invasive ,Pharmacology (medical) ,MIC distribution - Abstract
International audience; 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.
- Published
- 2022
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