Bennett John E, Izumikawa Koichi, Marr Kieren A
Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Antimicrob Agents Chemother. 2004 May;48(5):1773-7. doi: 10.1128/AAC.48.5.1773-1777.2004.
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.
光滑念珠菌可对氟康唑产生耐药性，在长期接触该药物期间导致持续定植和侵袭性感染。为确定这种情况下的耐药机制，在两年时间里，从接受氟康唑预防治疗的造血干细胞移植受者中每周采集口咽拭子进行光滑念珠菌培养。在20例患者中，至少相隔两周获得了两株相同核型的分离株，氟康唑的最低抑菌浓度（MIC）平均每31天翻倍。对20例研究患者中14例MIC至少有四倍变化的分离株的氟康唑耐药机制进行了研究。细胞耐药伴随着药物外排增加，表现为氟康唑和罗丹明6G的积累减少，以及两个药物转运蛋白CgCDR1和PDH1的转录本丰度增加。耐药性上升的速度和规律性表明，光滑念珠菌能够上调药物外排，而不丧失维持定植的能力。
