Barchiesi F, Arzeni D, Del Prete M S, Sinicco A, Falconi Di Francesco L, Pasticci M B, Lamura L, Nuzzo M M, Burzacchini F, Coppola S, Chiodo F, Scalise G
Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Ospedale Umberto Io, Italy.
J Antimicrob Chemother. 1998 May;41(5):541-8. doi: 10.1093/jac/41.5.541.
Over a 16 month period we conducted a prospective study in a cohort of 45 HIV-positive patients to detect the development of resistance to fluconazole and to analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were tested for their in-vitro susceptibility to fluconazole. Multiple strains of Candida albicans simultaneously isolated from a given patient were typed by electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7). Cure (complete resolution of signs and symptoms and negative post-treatment cultures) and improvement (complete resolution of signs and symptoms but positive post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes of OPC, respectively. Failure (absence of improvement or exacerbation of signs and symptoms) was observed in seven episodes (7%) from four patients. In two of these four patients a significant and progressive increase in fluconazole MICs was observed: from 0.25 to 16 mg/L in one patient, and from < or = 0.125 to 32 mg/L in the second one. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain different fluconazole MICs, indicating that, in order to avoid misleading results, one should perform in-vitro susceptibility testing by using a multiple colony inoculum rather than an inoculum made from a single colony. A total of 213 strains of C. albicans isolated from seven patients who suffered from four or more episodes of OPC through the course of the study were typed by electrophoretic karyotyping. Five individuals (71%) were infected with yeasts with only one DNA type, while the other two patients showed the presence of two or three different DNA types. The simultaneous presence of multiple types was found only in one of the seven subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the treatment of OPC in HIV patients. Isolation of fluconazole-resistant strains of C. albicans with this regimen is rare. The vast majority of HIV patients are infected with a unique strain of C. albicans throughout each episode of infection. A minority of patients, however, can harbour strains of C. albicans with variable patterns of fluconazole susceptibility simultaneously.
在16个月的时间里，我们对45名HIV阳性患者进行了一项前瞻性研究，以检测对氟康唑耐药性的发展情况，并分析口腔念珠菌病（OPC）的流行病学特征。每一次发作均采用口服氟康唑100mg/天，持续10天进行治疗。对所有酵母分离株进行了氟康唑体外药敏试验。从同一患者同时分离出的多株白色念珠菌通过电泳核型分析进行分型。总体而言，45名患者中共诊断出106次OPC发作：18/45名患者（40%）仅有一次发作，11/45名患者（24%）有两次发作，其余16/45名患者（36%）有三次或更多次发作（范围为3 - 7次）。OPC发作中分别有30/106次（28%）治愈（体征和症状完全消退且治疗后培养阴性）和69/106次（65%）改善（体征和症状完全消退但治疗后培养阳性）。4名患者的7次发作（7%）出现治疗失败（体征和症状无改善或加重）。在这4名患者中的2名患者中观察到氟康唑MIC显著且进行性升高：一名患者从0.25mg/L升至16mg/L，另一名患者从≤0.125mg/L升至32mg/L。对单个分离平板上的多个菌落进行检测表明，获得不同的氟康唑MIC并不罕见，这表明为避免产生误导性结果，应使用多个菌落接种物而非单个菌落接种物进行体外药敏试验。通过电泳核型分析对在研究过程中患有4次或更多次OPC发作的7名患者分离出的总共213株白色念珠菌进行了分型。5名个体（71%）感染的酵母只有一种DNA类型，而另外两名患者显示存在两种或三种不同的DNA类型。在7名受试者中仅1名发现同时存在多种类型。我们的数据证实了氟康唑100mg/天治疗HIV患者OPC的疗效。用该方案分离出耐氟康唑的白色念珠菌菌株的情况很少见。绝大多数HIV患者在每次感染发作期间均感染单一菌株的白色念珠菌。然而，少数患者可能同时携带对氟康唑敏感性模式不同的白色念珠菌菌株。
