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2020-02-11
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CRYPTOCOCCUS NEOFORMANS-CRYPTOCOCCUS GATTII SPECIES COMPLEX: AN INTERNATIONAL STUDY OF WILD-TYPE SUSCEPTIBILITY ENDPOINT DISTRIBUTIONS AND EPIDEMIOLOGICAL CUTOFF VALUES FOR FLUCONAZOLE, ITRACONAZOLE, POSACONAZOLE, AND VORICONAZOLE
Cryptococcus gattii
Fluconazole
Itraconazole
Posaconazole
Voriconazole
VCU Medical Center, Richmond, Virginia, USA; Hospital Universitario de Valme, Sevilla, Spainb; Unidad de Microbiologia Experimental, Hospital Universitario La Fe,Valencia, Spainc; Universidad Nacional Autónoma de Mexico, Distrito Federal, Méxicod; Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, Indiae; Departamento de Micología, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán,” Buenos Aires, Argentinaf; Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spaing; University of Texas Health Science Center, San Antonio, Texas, USAh; The University of Alberta, Edmonton, Alberta, Canadai; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africaj; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlandsk ; Institute of Tropical Medicine Pedro Kouri, Havana, Cubal; The HPA Mycology Reference Laboratory, Kingsdown, Bristol, United Kingdomm; Women’s and Children’s Hospital, Adelaide, South Australia, Australian ; The Innsbruck Medical University, Innsbruck, Austriao; Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USAp; The Adolfo Lutz Institute Public Health Reference Center, São Paulo and Rio Claro, Brazilq; Department of Medical Microbiology, Radboud University Medical Centre, Canisius Wilhelmina Hospital, Nijmegen, the Netherlandsr; University of Texas Health Science Center, Houston, Texas, USAs; Hospital General Universitario Gregorio Marañón, Faculty of Medicine-Universidad Complutense, Madrid, Spaint; University of Iowa, Iowa City, Iowa, USAu; Duke University Medical Center, Durham, North Carolina, USAv ; Laboratoire de Santé Publique du Québec, Canadaw; Instituto de Pesquisa Clinica Evandro Chagas-FIOCRUZ, Rio de Janeiro, Brazilx; and University of Adelaide, Adelaide, South Australia, Australiay.
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Abstract
Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wildtype (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359
MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included >95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformans nontyped and VNI) and 0.5 μg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Keywords
Cryptococcus neoformansCryptococcus gattii
Fluconazole
Itraconazole
Posaconazole
Voriconazole
Publisher
American Society for Microbiology
Citation
ESPINEL-INGROFF, A. et al. Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole. Antimicrobial Agents and Chemotherapy, v. 56, n. 11, p. 5898-5906, Nov. 2012.DOI
10.1128/AAC.01115-12ISSN
0066-4804Notes
L. Trilles. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.VCU Medical Center, Richmond, Virginia, USA; Hospital Universitario de Valme, Sevilla, Spainb; Unidad de Microbiologia Experimental, Hospital Universitario La Fe,Valencia, Spainc; Universidad Nacional Autónoma de Mexico, Distrito Federal, Méxicod; Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, Indiae; Departamento de Micología, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán,” Buenos Aires, Argentinaf; Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spaing; University of Texas Health Science Center, San Antonio, Texas, USAh; The University of Alberta, Edmonton, Alberta, Canadai; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africaj; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlandsk ; Institute of Tropical Medicine Pedro Kouri, Havana, Cubal; The HPA Mycology Reference Laboratory, Kingsdown, Bristol, United Kingdomm; Women’s and Children’s Hospital, Adelaide, South Australia, Australian ; The Innsbruck Medical University, Innsbruck, Austriao; Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USAp; The Adolfo Lutz Institute Public Health Reference Center, São Paulo and Rio Claro, Brazilq; Department of Medical Microbiology, Radboud University Medical Centre, Canisius Wilhelmina Hospital, Nijmegen, the Netherlandsr; University of Texas Health Science Center, Houston, Texas, USAs; Hospital General Universitario Gregorio Marañón, Faculty of Medicine-Universidad Complutense, Madrid, Spaint; University of Iowa, Iowa City, Iowa, USAu; Duke University Medical Center, Durham, North Carolina, USAv ; Laboratoire de Santé Publique du Québec, Canadaw; Instituto de Pesquisa Clinica Evandro Chagas-FIOCRUZ, Rio de Janeiro, Brazilx; and University of Adelaide, Adelaide, South Australia, Australiay.
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