Dannaoui E, Abdul M, Arpin M, Michel-Nguyen A, Piens M A, Favel A, Lortholary O, Dromer F
Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, CNRS FRE2849, Institut Pasteur, 25, rue du Dr. Roux, 75724 Paris Cedex 15, France.
Antimicrob Agents Chemother. 2006 Jul;50(7):2464-70. doi: 10.1128/AAC.01520-05.
The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.
在法国进行的一项多中心前瞻性研究中，采用不同技术（包括CLSI方法、Etest和酵母氮碱（YNB）培养基中的肉汤微量稀释法），测定了从连续的人类免疫缺陷病毒阳性和阴性患者中分离出的新型隐球菌菌株对氟康唑、两性霉素B和氟胞嘧啶等抗真菌药物的体外敏感性。评估了体外数据与抗真菌治疗开始2周后的临床结果之间的关系。此外，确定了菌株血清型与抗真菌药物体外活性之间的相关性，并比较了不同技术获得的药敏结果。37例患者接受两性霉素B与氟胞嘧啶联合作为一线治疗，22例仅接受两性霉素B治疗，15例仅接受氟康唑治疗。无论测试哪种抗真菌药物，与对给定治疗有反应的患者分离出的菌株相比，对于未对给定治疗产生反应的患者分离出的菌株，无论是采用CLSI方法、Etest还是YNB培养基中的肉汤微量稀释法，均未出现MIC升高的趋势。对于氟康唑和两性霉素B，通过CLSI或Etest方法获得的D血清型菌株的MIC显著低于A血清型菌株，而氟胞嘧啶的MIC根据血清型无差异。这些发现表明，用所使用的技术测定的新型隐球菌的体外抗真菌药敏性无法预测隐球菌病患者的早期临床结果。
