Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru

Bustamante Rufino, Ana Beatriz; Campos, Pablo E.; Illescas, Luis Ricardo; Posadas, Andres

dc.contributor.author	Bustamante Rufino, Ana Beatriz
dc.contributor.author	Illescas, Luis Ricardo
dc.contributor.author	Posadas, Andres
dc.contributor.author	Campos, Pablo E.
dc.date.accessioned	2019-08-08T15:23:46Z
dc.date.available	2019-08-08T15:23:46Z
dc.date.issued	2019
dc.identifier.uri	https://hdl.handle.net/20.500.12866/7153
dc.description.abstract	Azole resistance among Aspergillus fumigatus isolates, which is mainly related to mutations in the cyp51A gene, is a concern because it is rising, worldwide disseminated, and associated with treatment failure and death. Data on azole resistance of aspergillus from Latin American countries is very scarce and do not exist for Peru. Two hundred and seven Aspergillus clinical isolates collected prospectively underwent mycology and molecular testing for specie identification, and 143 isolates were confirmed as A. fumigatus sensu stricto (AFSS). All AFSS were tested for in vitro azole susceptibility, and resistant isolates underwent PCR amplification and sequencing of the whole cyp51A gene and its promoter. The in vitro susceptibility showed a minimal inhibitory concentration (MIC) range, MIC50 and MIC90 of 0.125 to >16, 0.25, and 0.5 μg/ml for itraconazole; 0.25 to 2, 0.5, and 0.5 μg/ml for voriconazole; and 0.003 to 1, 0.06, and 0.125 μg/ml for posaconazole. Three isolates (2%) showed resistance to itraconazole and exhibited different mutations of the cyp51A gene. One isolate harbored the mutation M220K, while a second one exhibited the G54 mutation plus a modification in the cyp51A gene promoter. The third isolate, from an azole naive patient, presented an integration of a 34-bp tandem repeat (TR34) in the promoter region of the gene and a substitution of leucine 98 by histidine (L98H). The three source patients had a diagnosis or suspicion of chronic pulmonary aspergillosis.	en_US
dc.language.iso	eng
dc.publisher	Oxford University Press
dc.relation.ispartofseries	Medical Mycology
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	Peru	en_US
dc.subject	Adolescent	en_US
dc.subject	Adult	en_US
dc.subject	Female	en_US
dc.subject	Humans	en_US
dc.subject	Male	en_US
dc.subject	Microbial Sensitivity Tests	en_US
dc.subject	Young Adult	en_US
dc.subject	Child, Preschool	en_US
dc.subject	Infant	en_US
dc.subject	aspergillosis	en_US
dc.subject	Aspergillus fumigatus	en_US
dc.subject	azole resistance	en_US
dc.subject	cyp51A gene	en_US
dc.subject	susceptibility testing	en_US
dc.subject	Aged	en_US
dc.subject	Middle Aged	en_US
dc.subject	Child	en_US
dc.subject	Prospective Studies	en_US
dc.subject	Qualitative Research	en_US
dc.subject	Aged, 80 and over	en_US
dc.subject	Drug Resistance, Multiple, Fungal	en_US
dc.subject	Antifungal Agents/pharmacology	en_US
dc.subject	Aspergillus fumigatus/drug effects/genetics	en_US
dc.subject	Azoles/pharmacology	en_US
dc.subject	Cytochrome P-450 Enzyme System/genetics	en_US
dc.subject	Fungal Proteins/genetics	en_US
dc.subject	Mutation	en_US
dc.subject	Pulmonary Aspergillosis/microbiology	en_US
dc.title	Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1093/mmy/myz032
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#4.03.00
dc.relation.issn	1460-2709