Tumbarello M, Caldarola G, Tacconelli E, Morace G, Posteraro B, Cauda R, Ortona L
Department of Infectious Diseases, Catholic University, Rome, Italy.
J Antimicrob Chemother. 1996 Oct;38(4):691-9. doi: 10.1093/jac/38.4.691.
The objective of this case-control study, conducted in a large Italian university hospital over a 12-month period, was to evaluate the risk factors associated with the emergence of azole resistant oral candidosis in 64 Human Immunodeficiency Virus (HIV) infected patients. A swab was obtained from each patient by brushing candidal lesions. Candida albicans was isolated in 41 patients (64%), Candida glabrata in ten (16%), Candida krusei in five (8%), Candida kefyr in two (3%), Candida tropicalis in two (3%), and Candida lipolytica and Candida guilliermondii in one case, respectively. Two patients suffered a double infection i.e. C. albicans+C. krusei and C. albicans+C. glabrata, respectively. Candida species were tested in vitro for their susceptibility to ketoconazole, fluconazole, itraconazole and amphotericin B. MICs of the four antifungal drugs were obtained for each yeast using a microdilution broth method developed in our laboratory. Twenty four (37%) of the isolated strains were resistant both to itraconazole and fluconazole, five (8%) to fluconazole alone, and two (3%) to ketoconazole alone, while none of the isolated strains was resistant to amphotericin B. Patients with oral candidosis caused by a strain resistant to one or more azole drug were compared to control patients with azole-susceptible oral candidosis. On univariate analysis, more than five episodes of oral candidosis in the last year (P = 0.01), previous use of azole therapy (P = 0.001), C2-3 category of HIV infection (P = 0.01) and low number of circulating CD4+ T-cells (P = 0.03) were significantly associated with an increased risk for the development of azole resistance. However, previous use of azole therapy was the only factor selected by a stepwise logistic regression analysis which was independently associated with the isolation of azole resistant strains (P = 0.003). Our findings indicate that, in view of the potential risk for the emergence and selection of azole resistant strains of Candida in patients with AIDS, it is important to carefully choose the antifungal drug for the therapy of mild fungal infections after evaluation of the in-vitro susceptibility of the isolated strains.
这项病例对照研究在一家大型意大利大学医院进行，为期12个月，目的是评估64例感染人类免疫缺陷病毒（HIV）的患者中与唑类耐药口腔念珠菌病出现相关的危险因素。通过擦拭念珠菌病变部位从每位患者获取拭子。41例患者（64%）分离出白色念珠菌，10例（16%）为光滑念珠菌，5例（8%）为克柔念珠菌，2例（3%）为凯菲念珠菌，2例（3%）为热带念珠菌，1例分别为解脂念珠菌和季也蒙念珠菌。2例患者分别遭受双重感染，即白色念珠菌+克柔念珠菌和白色念珠菌+光滑念珠菌。对念珠菌属进行体外酮康唑、氟康唑、伊曲康唑和两性霉素B敏感性测试。使用我们实验室开发的微量稀释肉汤法获得每种酵母的四种抗真菌药物的最低抑菌浓度（MIC）。分离出的菌株中有24株（37%）对伊曲康唑和氟康唑均耐药，5株（8%）仅对氟康唑耐药，2株（3%）仅对酮康唑耐药，而分离出的菌株中无一株对两性霉素B耐药。将由对一种或多种唑类药物耐药的菌株引起口腔念珠菌病的患者与唑类敏感口腔念珠菌病的对照患者进行比较。单因素分析显示，过去一年中口腔念珠菌病发作超过5次（P = 0.01）、既往使用唑类治疗（P = 0.001）、HIV感染的C2 - 3类别（P = 0.01）和循环CD4 + T细胞数量低（P = 0.03）与唑类耐药发生风险增加显著相关。然而，既往使用唑类治疗是逐步逻辑回归分析中唯一选择的与分离出唑类耐药菌株独立相关的因素（P = 0.003）。我们的研究结果表明，鉴于艾滋病患者中念珠菌唑类耐药菌株出现和选择的潜在风险，在评估分离菌株的体外敏感性后，谨慎选择抗真菌药物用于轻度真菌感染的治疗非常重要。
