1. Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru
- Author
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Beatriz Bustamante, Andrés Posadas, Pablo E. Campos, and Luis Ricardo Illescas
- Subjects
Azoles ,Male ,Posaconazole ,Antifungal Agents ,Cytochrome P-450 Enzyme System/genetics ,Aspergillosis ,Aspergillus fumigatus ,Cytochrome P-450 Enzyme System ,Peru ,aspergillosis ,Prospective Studies ,Child ,cyp51A gene ,Qualitative Research ,chemistry.chemical_classification ,Aged, 80 and over ,0303 health sciences ,Pulmonary Aspergillosis/microbiology ,biology ,Chronic pulmonary aspergillosis ,General Medicine ,susceptibility testing ,Middle Aged ,Fungal Proteins/genetics ,Infectious Diseases ,Child, Preschool ,Aspergillus fumigatus/drug effects/genetics ,Antifungal Agents/pharmacology ,purl.org/pe-repo/ocde/ford#4.03.00 [https] ,Female ,medicine.drug ,Adult ,Adolescent ,Itraconazole ,Microbial Sensitivity Tests ,purl.org/pe-repo/ocde/ford#3.03.08 [https] ,Microbiology ,Fungal Proteins ,03 medical and health sciences ,Young Adult ,azole resistance ,Drug Resistance, Multiple, Fungal ,medicine ,Humans ,030304 developmental biology ,Aged ,Voriconazole ,Aspergillus ,Azoles/pharmacology ,030306 microbiology ,Infant ,medicine.disease ,biology.organism_classification ,chemistry ,Mutation ,Azole ,Pulmonary Aspergillosis - 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.
- Published
- 2019