title: Molecular characterisation and antifungal susceptibility of clinical Cryptococcus deuterogattii (AFLP6/VGII) isolates from Southern Brazil.
abstract: Cryptococcosis, caused by Cryptococcus gattii sensu lato, is an emerging disease that was initially found in (sub)tropical regions but recently expanded to temperate regions. Cryptococcus gattii s.l. infections are mostly encountered in healthy individuals, frequently affecting both lungs and the central nervous system (CNS). Usually, C. gattii s.l. is less susceptible to antifungal compounds than its counterpart, C. neoformans s.l. We studied 18 clinical C. gattii s.l. isolates with amplified fragment length polymorphism (AFLP) fingerprinting, mating-typing, multi-locus sequence typing (MLST) and antifungal susceptibility testing. All isolates were C. deuterogattii (genotype AFLP6/VGII), 14 were mating-type α and four were type a. Amphotericin B, itraconazole, voriconazole, posaconazole and isavuconazole showed high activity, with minimum inhibitory concentration (MIC) ranges of 0.063-0.25, 0.031-0.25, 0.031-0.25, 0.031-0.25 and <0.016-0.25 μg mL-1, respectively. Fluconazole and flucytosine had high geometric mean MICs of 2.07 and 3.7 μg mL-1, respectively. Most cases occurred in immunocompetent patients (n = 10; 55.6 %) and CNS involvement was the most common clinical presentation (n = 14; 77.8 %). Three patients (16.7 %) showed sequelae, hyperreflexia, dysarthria, diadochokinesia, anosmia and upper limb weakness. In conclusion, all infections were caused by C. deuterogattii (AFLP6/VGII) and the majority of patients were immunocompetent, with the CNS as the most affected site. All antifungal drugs had high in vitro activity against C. deuterogattii isolates, except fluconazole and flucytosine.
authors.affiliation: Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Parana, Curitiba, PR, Brazil.|Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, The Netherlands.
authors.forename: P F
authors.initials: PF
authors.lastname: Herkert
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, The Netherlands. f.hagen@cwz.nl.
authors.forename: F
authors.identifier: http://orcid.org/0000-0002-5622-1916
authors.initials: F
authors.lastname: Hagen
authors.affiliation: Department of Internal Medicine, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: G L
authors.initials: GL
authors.lastname: de Oliveira Salvador
authors.affiliation: Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Parana, Curitiba, PR, Brazil.|Department of Biological Science, State University of Parana/Campus Paranagua, Paranagua, PR, Brazil.
authors.forename: R R
authors.initials: RR
authors.lastname: Gomes
authors.affiliation: Federal University of Uberlandia, Uberlândia, MG, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Parana, Curitiba, PR, Brazil.|Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, DF, Brazil.
authors.forename: V A
authors.initials: VA
authors.lastname: Vicente
authors.affiliation: Laboratory of Mycology, Hospital de Clínicas, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: M D
authors.initials: MD
authors.lastname: Muro
authors.affiliation: Laboratory of Mycology, Hospital de Clínicas, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: R L
authors.initials: RL
authors.lastname: Pinheiro
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, The Netherlands.|Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Meis
authors.affiliation: Communitarian Health Department, Hospital de Clínicas, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Queiroz-Telles
mesh_terms: D054458:Amplified Fragment Length Polymorphism Analysis; D000935:Antifungal Agents / Q000494:pharmacology*; D001938:Brazil / Q000453:epidemiology; D003453:Cryptococcosis / Q000453:epidemiology / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016172:DNA Fingerprinting; D025141:Drug Resistance, Fungal; D005260:Female; D049770:Genes, Mating Type, Fungal; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing
chemical_list: D000935:Antifungal Agents