Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis
Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis
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DOI：
10.1128/aac.48.5.1773-1777.2004
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发表时间：
2004-05-01
影响因子：
4.9
通讯作者：
Marr, KA
中科院分区：
文献类型：
--
作者：
Bennett, JE;Izumikawa, K;Marr, KA
光滑念珠菌可对氟康唑产生耐药性，在长期暴露于药物期间引起持续定植和侵袭性感染。为了确定这种情况下的耐药机制，每周进行口咽培养。glabrata从接受氟康唑预防的造血干细胞移植受者获得2年时间。在20例患者中，至少有两个相同核型的分离株，间隔超过两周，氟康唑MIC平均每31天翻一番。研究了20例MIC变化至少4倍的患者中14例的分离株对氟康唑耐药的机制。细胞耐药性伴随着增加药物外排，如通过减少氟康唑和罗丹明6G的积累和增加来自两种药物转运蛋白CgCDR 1和PDH 1的转录物丰度来测量。阻力上升的速度和规律性表明，C. glabrata能够上调药物外排而不丧失维持定殖的能力。
Candida glabrata can become resistant to fluconazole, causing persistent colonization and invasive infection during prolonged exposure to the drug. To determine the mechanism of resistance in this setting, weekly oropharyngeal cultures for C. glabrata were obtained over a 2-year period from hematopoietic stem cell transplant recipients who were receiving fluconazole prophylaxis. In 20 patients from whom at least two isolates of the same karyotype were obtained more than two weeks apart, fluconazole MICs doubled every 31 days on average. The mechanism of fluconazole resistance in isolates from the 14 of the 20 patients studied in whom MICs changed at least fourfold was studied. Cellular resistance was accompanied by increased drug efflux as measured by decreased accumulation of fluconazole and rhodamine 6G and increased abundance of transcripts from two drug transporters, CgCDR1 and PDH1. The rapidity and regularity of the rising resistance indicated that C. glabrata is able to upregulate drug efflux without losing the ability to maintain colonization.