In Vitro Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa
In Vitro Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa
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DOI：
10.1128/aac.00517-21
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发表时间：
2021-09-01
影响因子：
4.9
通讯作者：
Govender, Nelesh P.
中科院分区：
文献类型：
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作者：
Maphanga, Tsidiso G.;Naicker, Serisha D.;Govender, Nelesh P.
假丝酵母菌是一种耐多药真菌病原体，在南非医院流行。我们测试了2016年和2017年提交给国家实验室进行白念珠菌血症监测的金黄色葡萄球菌分离株。我们通过表型/分子方法确认了该菌株的物种鉴定。我们用肉汤微量稀释法和Etest法检测了两性霉素B、阿尼达芬净、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。我们使用试探性断点来解释MIC。我们对一组分离物的基因组进行了测序，并将它们与金黄色葡萄球菌B8441参考菌株进行了比较。400株卷曲葡萄球菌中，361株(90%)对至少一种抗真菌药物耐药，339株(94%)对氟康唑耐药(MIC=32mU g/ml)，19株(6%)对氟康唑和两性霉素B耐药(MIC=32mU g/ml)，1株(0.3%)对两性霉素B耐药。来自同一患者的两株(05%)分离株为泛耐药(对氟康唑、两性霉素B和棘球菌素类耐药)。在进行全基因组测序的92个菌株中，77个菌株聚集在Glade III，包括泛抗性菌株，13个菌株聚集在Glade I，2个菌株聚集在Glade IV。84个菌株(91%)至少对一种抗真菌药物具有抗性；耐药和敏感菌株都有突变。ERG11中的VF125AL、Y132F、K177R、N335S和E343D；MRR1中的N647T；TAC1b中的A651P、A657V和S195G；FIGIHP1中的S639P；ERGS中的S58T。大多数南非C-Auris分离株对氮唑类药物具有抗药性，但对多烯和棘球菌素的抗药性较少。我们观察到耐药基因的突变，甚至在表型敏感的菌株中也是如此。
Candida awls 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. curls isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of >= 32 mu g/ml), 19 (6%) to fluconazole and amphotericin B (MICs of >= 32 mu g/ml), and 1 (0.3%) to amphotericin B alone. Two (05%) 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 Glade III, including the pan-resistant isolates, 13 in Glade I, and 2 in Glade 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 ERG11; N647T in MRR1; A651P, A657V, and S195G in TAC1b; S639P in FIGIHP1; and S58T in ERGS. 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.