title: First itraconazole resistant Aspergillus fumigatus clinical isolate harbouring a G54E substitution in Cyp51Ap in South America.
abstract: BACKGROUND
  A 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus.
  
  
  METHODS
  Specimens were collected for microscopy examination and culture. The isolate was identified by morphological and molecular criteria. Susceptibility testing was performed using CLSI methods. CYP51A gene was PCR amplified and sequenced.
  
  
  RESULTS
  An Aspergillus fumigatus strain resistant to itraconazole (MIC>8μg/ml) was isolated. The isolate was susceptible to amphotericin B, posaconazole, voriconazole and caspofungin. CYP51A sequencing showed two mutations leading on the G54E substitution. The patient received natamycin as treatment.
  
  
  CONCLUSIONS
  This is the first report in South America of a clinical A. fumigatus strain carrying the substitution G54E at Cyp51Ap associated with itraconazole resistance. Considering the patient was azole-naive, this resistant isolate may have been acquired from the environment.
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT- Santa Fe, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Leonardelli
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Theill
authors.affiliation: Hospital "JM Cullen", Santa Fe, Argentina.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Nardin
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Daiana
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT- Santa Fe, Argentina.
authors.forename: Catiana
authors.initials: C
authors.lastname: Dudiuk
authors.affiliation: Hospital "JM Cullen", Santa Fe, Argentina.
authors.forename: Emilce
authors.initials: E
authors.lastname: Mendez
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Soledad
authors.initials: S
authors.lastname: Gamarra
authors.affiliation: Laboratorio de Micología y Diagnóstico Molecular - Cátedra de Parasitología y Micología - Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT- Santa Fe, Argentina. Electronic address: ggarcia@unl.edu.ar.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Effron
mesh_terms: D000328:Adult; D001228:Aspergillosis / Q000097:blood* / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal; D015821:Eye Infections, Fungal / Q000188:drug therapy / Q000382:microbiology*; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology* / Q000627:therapeutic use; D007634:Keratitis / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D009154:Mutation; D013020:South America
chemical_list: D005656:Fungal Proteins; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus
keywords: Aspergillus fumigatus; Azole resistance; CYP51; Resistencia a azoles