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曲霉及相关菌种中的唑类耐药性:一个新出现的问题还是罕见现象?

Azole-Resistance in and Related Species: An Emerging Problem or a Rare Phenomenon?

作者信息

Zoran Tamara, Sartori Bettina, Sappl Laura, Aigner Maria, Sánchez-Reus Ferran, Rezusta Antonio, Chowdhary Anuradha, Taj-Aldeen Saad J, Arendrup Maiken C, Oliveri Salvatore, Kontoyiannis Dimitrios P, Alastruey-Izquierdo Ana, Lagrou Katrien, Cascio Giuliana Lo, Meis Jacques F, Buzina Walter, Farina Claudio, Drogari-Apiranthitou Miranda, Grancini Anna, Tortorano Anna M, Willinger Birgit, Hamprecht Axel, Johnson Elizabeth, Klingspor Lena, Arsic-Arsenijevic Valentina, Cornely Oliver A, Meletiadis Joseph, Prammer Wolfgang, Tullio Vivian, Vehreschild Jörg-Janne, Trovato Laura, Lewis Russell E, Segal Esther, Rath Peter-Michael, Hamal Petr, Rodriguez-Iglesias Manuel, Roilides Emmanuel, Arikan-Akdagli Sevtap, Chakrabarti Arunaloke, Colombo Arnaldo L, Fernández Mariana S, Martin-Gomez M Teresa, Badali Hamid, Petrikkos Georgios, Klimko Nikolai, Heimann Sebastian M, Uzun Omrum, Roudbary Maryam, de la Fuente Sonia, Houbraken Jos, Risslegger Brigitte, Lass-Flörl Cornelia, Lackner Michaela

机构信息

Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.

Servei de Microbiologia, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.

出版信息

Front Microbiol. 2018 Mar 28;9:516. doi: 10.3389/fmicb.2018.00516. eCollection 2018.

DOI:10.3389/fmicb.2018.00516
PMID:29643840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5882871/
Abstract

Invasive mold infections associated with species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the section followed by members of the section . The frequency of and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. A global set ( = 498) of and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the gene. The majority of isolates was identified as (86.8%), followed by (8.4%), (2.6%), (1.6%), (0.2%), and (0.2%). One isolate failed to match a known sp., but was found most closely related to . According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one and one isolate. The most affected amino acid position of the gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. was most prevalent, followed by . Posaconazole was the most potent drug against , but 5.4% of showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

摘要

与该菌种相关的侵袭性霉菌感染是免疫功能低下患者死亡的重要原因。最常见的病原体是该属某组的成员,其次是另一组的成员。临床标本中该菌种及相关(隐性)菌种的出现频率以及唑类耐药菌株的百分比仍有待研究。对一组全球范围的(n = 498)该菌种及表型相关分离株进行了分子鉴定(β-微管蛋白),检测了它们对泊沙康唑、伏立康唑和伊曲康唑的抗真菌药敏性,并将耐药表型与该基因中的点突变相关联。大多数分离株被鉴定为该菌种(86.8%),其次是另一菌种(8.4%)、又一菌种(2.6%)、再一菌种(1.6%)、某菌种(0.2%)和另一菌种(0.2%)。一株分离株与已知的该属菌种不匹配,但发现与另一菌种关系最为密切。根据欧盟CAST临床断点,在所有测试分离株中,5.4%检测出唑类耐药,该菌种中有6.2%对泊沙康唑耐药。泊沙康唑耐药存在地域差异,在捷克共和国、希腊和土耳其为0%,在德国为13.7%。相比之下,隐性菌种中的唑类耐药很少见,66株分离株中有2株,仅在一株该菌种和一株另一菌种分离株中观察到。与泊沙康唑耐药表型相关的该基因中受影响最大的氨基酸位置是M217,在M217T和M217V变异中发现。该菌种最为普遍,其次是另一菌种。泊沙康唑是对抗该菌种最有效的药物,但该菌种中有5.4%对这种唑类耐药。在奥地利、德国和英国,所有该菌种分离株中的泊沙康唑耐药率高于10%,对伏立康唑耐药很少见,对伊曲康唑则无耐药情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/5882871/468651799875/fmicb-09-00516-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/5882871/e9eb50980e9b/fmicb-09-00516-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/5882871/468651799875/fmicb-09-00516-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/5882871/e9eb50980e9b/fmicb-09-00516-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/5882871/468651799875/fmicb-09-00516-g0002.jpg

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