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南非血流感染分离的耳念珠菌的抗真菌耐药性。

Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa.

机构信息

National Institute for Communicable Diseases, Centre for Healthcare-Associated Infections, Antimicrobial Resistance, and Mycoses, National Health Laboratory Servicegrid.416657.7, Johannesburg, South Africa.

School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

出版信息

Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0051721. doi: 10.1128/AAC.00517-21.

Abstract

Candida auris is a multidrug-resistant fungal pathogen that is endemic in South African hospitals. We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidemia in 2016 and 2017. We confirmed the species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using broth microdilution and Etest methods. We interpreted MICs using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared them to the C. auris B8441 reference strain. Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of ≥32 µg/ml), 19 (6%) to fluconazole and amphotericin B (MICs of ≥2 µg/ml), and 1 (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (resistant to fluconazole, amphotericin B, and echinocandins). Of 92 isolates selected for whole-genome sequencing, 77 clustered in clade III, including the pan-resistant isolates, 13 in clade I, and 2 in clade IV. Eighty-four of the isolates (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, and E343D in ; N647T in ; A651P, A657V, and S195G in ; S639P in ; and S58T in . Most South African C. auris isolates were resistant to azoles, although resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically susceptible isolates.

摘要

耳念珠菌是一种多药耐药的真菌病原体,在南非的医院中流行。我们测试了 2016 年和 2017 年提交给参考实验室进行国家基于实验室的念珠菌血症监测的血流耳念珠菌分离株。我们通过表型/分子方法确认了物种鉴定。我们使用肉汤微量稀释法和 Etest 方法测试了两性霉素 B、阿尼芬净、卡泊芬净、米卡芬净、伊曲康唑、泊沙康唑、伏立康唑、氟康唑和氟胞嘧啶的敏感性。我们使用暂定的断点来解释 MIC 值。我们对一组分离株进行了基因组测序,并将其与耳念珠菌 B8441 参考株进行了比较。在 400 株耳念珠菌分离株中,有 361 株(90%)对至少一种抗真菌药物耐药,有 339 株(94%)单独对氟康唑耐药(MIC 值≥32μg/ml),有 19 株(6%)对氟康唑和两性霉素 B 耐药(MIC 值≥2μg/ml),有 1 株(0.3%)单独对两性霉素 B 耐药。来自单个患者的 2 株(0.5%)分离株为泛耐药(对氟康唑、两性霉素 B 和棘白菌素均耐药)。在选择进行全基因组测序的 92 株分离株中,有 77 株聚类在第三组,包括泛耐药株,有 13 株在第一组,有 2 株在第四组。84 株(91%)分离株至少对一种抗真菌药物耐药;耐药和敏感分离株均有突变。不同组中发现的常见取代是 VF125AL、Y132F、K177R、N335S 和 E343D 在 ;N647T 在 ;A651P、A657V 和 S195G 在 ;S639P 在 ;S58T 在 。虽然对多烯类和棘白菌素的耐药性较少见,但南非的大多数耳念珠菌分离株对唑类药物耐药。即使在表型敏感的分离株中,我们也观察到了耐药基因的突变。

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