Moran G P, Sullivan D J, Henman M C, McCreary C E, Harrington B J, Shanley D B, Coleman D C
Department of Oral Medicine and Pathology, School of Dental Science, Trinity College, University of Dublin, Republic of Ireland.
Antimicrob Agents Chemother. 1997 Mar;41(3):617-23. doi: 10.1128/AAC.41.3.617.
Candida dubliniensis is a recently described species of Candida associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. Nineteen oral isolates of C. dubliniensis recovered from 10 HIV-positive and 4 HIV-negative individuals and one vaginal isolate from an additional HIV-negative subject were assessed for fluconazole susceptibility by broth microdilution (BMD), hyphal elongation assessment, and Etest. The susceptibilities of these 20 isolates to itraconazole and amphotericin B and of 10 isolates to ketoconazole were also determined by BMD only. Sixteen of the C. dubliniensis isolates were susceptible to fluconazole (MIC range, 0.125 to 1.0 microgram ml-1), and four (recovered from two AIDS patients) were fluconazole resistant (MIC range, 8 to 32 micrograms ml-1). Fluconazole susceptibility data obtained by hyphal elongation assessment correlated well with results obtained by BMD, but the corresponding Etest MIC results were one to four times higher. All of the isolates tested were found to be sensitive to itraconazole, ketoconazole, and amphotericin B. Sequential exposure of two fluconazole-sensitive (MIC, 0.5 microgram ml-1) C. dubliniensis isolates to increasing concentrations of fluconazole in agar medium resulted in the recovery of derivatives which expressed a stable fluconazole-resistant phenotype (BMD-determined MIC range, 16 to 64 micrograms ml-1), even after a minimum of 10 consecutive subcultures on drug-free medium and following prolonged storage at -70 degrees C. The clonal relationship between the parental isolates and their respective fluconazole-resistant derivatives was confirmed by genomic DNA fingerprinting and karyotype analysis. The results of this study demonstrate that C. dubliniensis is inherently susceptible to commonly used antifungal drugs, that fluconazole resistance does occur in clinical isolates, and that stable fluconazole resistance can be readily induced in vitro following exposure to the drug.
都柏林念珠菌是一种最近被描述的念珠菌属物种，与人类免疫缺陷病毒（HIV）感染个体的口腔念珠菌病有关。从10名HIV阳性个体和4名HIV阴性个体中分离出的19株都柏林念珠菌口腔菌株，以及从另一名HIV阴性个体中分离出的1株阴道菌株，通过肉汤微量稀释法（BMD）、菌丝伸长评估和Etest法评估其对氟康唑的敏感性。这20株菌株对伊曲康唑和两性霉素B的敏感性以及10株菌株对酮康唑的敏感性也仅通过BMD法测定。16株都柏林念珠菌菌株对氟康唑敏感（MIC范围为0.125至1.0微克/毫升），4株（从两名艾滋病患者中分离出）对氟康唑耐药（MIC范围为8至32微克/毫升）。通过菌丝伸长评估获得的氟康唑敏感性数据与BMD法获得的结果相关性良好，但相应的Etest MIC结果高1至4倍。所有测试的菌株对伊曲康唑、酮康唑和两性霉素B均敏感。将两株对氟康唑敏感（MIC为0.5微克/毫升）的都柏林念珠菌菌株在琼脂培养基中依次暴露于浓度递增的氟康唑中，即使在无药培养基上连续传代至少10次并在-70℃长期保存后，也能获得表达稳定氟康唑耐药表型的衍生物（BMD测定的MIC范围为16至64微克/毫升）。通过基因组DNA指纹图谱和核型分析证实了亲本菌株与其各自的氟康唑耐药衍生物之间的克隆关系。本研究结果表明，都柏林念珠菌对常用抗真菌药物具有固有敏感性，临床分离株中确实存在氟康唑耐药性，并且在体外接触该药物后很容易诱导出稳定的氟康唑耐药性。
