Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient.
Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient.
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DOI：
10.1111/j.1601-0825.1997.tb00336.x
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发表时间：
1997-05
期刊：
影响因子：
3.8
通讯作者：
TC White;M. Pfaller;M. Rinaldi;J. Smith;S. Redding
中科院分区：
文献类型：
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作者：
TC White;M. Pfaller;M. Rinaldi;J. Smith;S. Redding
口腔念珠菌病是hiv感染者免疫系统衰竭的最早和最常见的并发症之一。多年来，口服念珠菌病已有效地治疗与唑类药物，其中最常用的是氟康唑。不幸的是，广泛使用该药进行治疗和预防已导致越来越多的患者治疗失败。在大多数病例中，从感染中分离出的白色念珠菌菌株对氟康唑不太敏感。白色念珠菌菌株对唑的耐药性的发展已经进行了生物化学和最近的分子技术研究。白色念珠菌在2年内从同一患者分离出17株白色念珠菌，这是一个很好的例子，说明了白色念珠菌对唑的耐药性。在此期间，患者经历了14次口腔念珠菌病发作，并接受了氟康唑剂量增加的治疗。分子和生化分析证实，这些分离株是同一株白色念珠菌，并且这些分离株的耐药性在600代以上是稳定的，这表明该菌株的变化本质上是遗传的。此外，利用中度重复探针Ca3进行限制性片段长度多态性（RFLP）分析发现，抗性的发展与原菌株的子菌株或变体的鉴定相关。对这一系列分离株的分析表明，唑耐药性与几个小的遗传变化有关，每个遗传变化都有助于菌株的整体耐药性。显然，患者持续使用唑类药物可以选择使口腔念珠菌病难以治疗的基因改变。
Oral candidiasis is one of the earliest and most frequent complications of a failing immune system in HIV-infected individuals. For several years, oral candidiasis has been treated effectively with azole drugs, the one most frequently used is fluconazole. Unfortunately, extensive use of the drug for treatment and prophylaxis has led to treatment failure in an increasing number of patients. In most of these cases, strains of C. albicans isolated from the infection are less susceptible to fluconazole. The development of azole resistance in strains of C. albicans has been studied biochemically and more recently with molecular techniques. One excellent example of the development of azole resistance in C. albicans has been documented in a series of 17 C. albicans isolates from a single patient over a 2-year period. During this time, the patient experienced 14 episodes of oral candidiasis and was treated with increasing doses of fluconazole. Molecular and biochemical analyses confirms that the isolates are the same strain of C. albicans and that the resistance in these isolates is stable over 600 generations, suggesting that the changes in this strain are genetic in nature. In addition, the development of resistance is correlated with the identification of a substrain or variant of the original strain, as identified by restriction fragment length polymorphism (RFLP) analysis with the moderately repetitive probe, Ca3. The analysis of this series of isolates demonstrates that azole drug resistance is associated with several small genetic changes, each of which contributes to the overall resistance of the strain. Clearly, continual use of azole drugs by a patient can select for genetic changes that render oral candidiasis refractory to treatment.