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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates
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Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

机译：氟康唑-不易感热带假丝酵母菌株与氟康唑-易感性孤立菌株的耐药机制和临床特征

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摘要

We investigated the azole resistance mechanisms and clinical features of fluconazole-nonsusceptible (FNS) isolates of Candida tropicalis recovered from Korean surveillance cultures in comparison with fluconazole-less-susceptible (FLS) isolates. Thirty-five clinical isolates of C. tropicalis, comprising 9 FNS (fluconazole MIC, 4 to 64 mu g/ml), 12 FLS (MIC, 1 to 2 mu g/ml), and 14 control (MIC, 0.125 to 0.5 mu g/ml) isolates, were assessed. CDR1, MDR1, and ERG11 expression was quantified, and the ERG11 and UPC2 genes were sequenced. Clinical features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both FNS and FLS isolates had> 10-fold higher mean expression levels of CDR1, MDR1, and ERG11 genes than control isolates (P values of< 0.02 for all). When FNS and FLS isolates were compared, FNS isolates had 3.4-fold higher mean ERG11 expression levels than FLS isolates (P = 0.004), but there were no differences in those of CDR1 or MDR1. Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11 FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus 4/10), but FNS isolates were identified more frequently from patients with previous azole exposure (6/6 versus 3/10; P = 0.011) and immunosuppression (6/6 versus 3/10; P = 0.011). These results reveal that the majority of FNS C. tropicalis isolates show overexpression of CDR1, MDR1, and ERG11 genes, and fungemia develops after azole exposure in patients with immunosuppression.
机译：我们调查了从韩国监测培养物中回收的热带假丝酵母对氟康唑不敏感（FNS）分离株与不敏感氟康唑的分离株对唑的耐药机制和临床特征。 35种热带念珠菌临床分离株，包括9种FNS（氟康唑MIC，4至64μg / ml），12种FLS（MIC，1至2μg/ ml）和14种对照（MIC，0.125至0.5μg） （g / ml）分离物进行了评估。定量CDR1，MDR1和ERG11表达，并对ERG11和UPC2基因进行测序。分析了16例FNS或FLS血流分离株的患者的临床特征。 FNS和FLS分离株的CDR1，MDR1和ERG11基因平均表达水平均比对照分离株高10倍（所有P值均<0.02）。比较FNS和FLS分离株时，FNS分离株的平均ERG11表达水平比FLS分离株高3.4倍（P = 0.004），但CDR1或MDR1的表达水平没有差异。在所有35个分离株中，分别有4个（2个FNS和2个FLS）和28个（8个FNS，11个FLS和9个对照）分离株在Erg11p和Upc2p中显示出氨基酸取代。 FNS和FLS血流分离物均与唑类治疗失败（3/4对4/7）或未清除的真菌血症（4/6对4/10）相关，但FNS分离物在先前曾接触过唑类的患者中更经常被发现（6 / 6对3/10; P = 0.011）和免疫抑制（6/6对3/10; P = 0.011）。这些结果表明，大多数FNS热带假丝酵母菌株均显示CDR1，MDR1和ERG11基因的过表达，并且在免疫抑制患者中接受吡唑类药物后会出现真菌病。

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