國家衛生研究院 NHRI:Item 3990099045/10924

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Title:	Prevalence and resistance mechanisms of clinical azole-resistant Aspergillus fumigatus, Taiwan
Authors:	Wu, CJ;Liu, WL;Ko, WC;Wang, HC;Hsieh, MI;Dai, CT;Choi, PC;Yang, JL;Chen, YC;TSAR Hosptials.
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	Background: Azole-resistant Aspergillus fumigatus (ARAF) has become a growing public health concern. International consensus suggests that empirical therapy for A. fumigatus aspergillosis should be guided by the local clinical and environmetal resistance rate. This study investiagted the current status of aozle resistance among A. fumigatus clinical isolates in Taiwan. Methods: A multicenter collection of A. fumigatus clinical isolates has been coducted during 2011–2016. A. fumigatus sensu stricto was confirmed by sequence analysis of the ITS and calmodulin genes. Minimal inhibitory concentrations (MICs) of itraconazole, voriconazole, posaconazole, and amphotericin B were determined using the CLSI M38-A2 broth microdilution method. All ARAF isolates were examined for cyp51A mutations and, if typical cyp51A mutation was not identified, cyp51A-independent resistance mechanisms, including mutations in hapE or srbA by sequence anslysis and upregulation of cyp51B and drug efflux transporters (AfuMDR1, AfuMDR2, AfuMDR3, AfuMDR4, atrF, cdr1B, and mfs56) by real-time PCR using a biofilm model. Genotypic relationships between strains were investigated using a microsatellite genotyping method. Results: A total of 274 clinical A. fumigatus isolates have been collected from 210 patients. Fifteen isolates from nine patients displayed multi-azole resistance, and all remained susceptible to amphotericin B. The prevalence rates of azole resistance were 5.5% and 4.3% based on isolates and patients, respectively. Of 15 ARAF isolates, 11 (73%) isolates from 8 (89%) patients carried TR 34 /L98H mutation in cyp51A, an environmental mutation linked to azole fungicide usage; of three patients with known medical history, all were azole-naïve. The remaining 4 ARAF isolates were sequential isolates from a HIV-infected patient presented with A. fumigatus renal abscess chronically treated with voriconazole for documented azole susceptibility of the initial A. fumigatus isolate (strain YL1). The four ARAF strains had much higher basal and induced expression levels of Cdr1B transporter than azole-susceptible reference strains and strain YL1, suggesting that upregulation ofCdr1B transporter may be involved in azole resistance. Phylogenetical analysis revealed genetic diversity of ARAF clinical isolates with TR 34 /L98H mutation in Taiwan, most of which have evolved locally and differed from oversea TR 34 /L98H strains. Of note, most of clinical TR 34 /L98H isolates found here can be linked to isogenic or near-isogenic environmental TR 34 /L98H isolates from Taiwan. Conclusion: The prevalence of azole resistance in A. fumigatus clinical isolates remained uncommon in Taiwan. However, azoleresistant aspergillosis should be considered for cases fail azole therapy due to either the acquisition of extant environmental TR 34 / L98H isolates, or acquired azole resistance during azole treatment.
Date:	2017-11
Relation:	International Journal of Antimicrobial Agents. 2017 Nov;50(Suppl. 2):S158.
Link to:	http://dx.doi.org/10.1016/S0924-8579(17)30423-5
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0924-8579&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000416028900387
Appears in Collections:	[Chi-Jung Wu] Conference Papers/Meeting Abstract

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