Atkinson B A, Bouthet C, Bocanegra R, Correa A, Luther M F, Graybill J R
Department of Medicine, University of Texas Health Science Center at San Antonio, USA.
J Antimicrob Chemother. 1995 May;35(5):631-40. doi: 10.1093/jac/35.5.631.
Candida glabrata is an emerging opportunist pathogen in immunosuppressed patients. C. glabrata is resistant to many antifungal agents and until recently, there have been no standard treatment regimens for this organism. A mouse model was established using mice immunosuppressed with 5 fluorouracil to evaluate amphotericin B, flucytosine, fluconazole and their combinations to treat an intravenously induced C. glabrata infection. Treatment with fluconazole, flucytosine, amphotericin B or a combination was begun one day after infection. Following 5 days of treatment, the mice were killed for fungal counts in kidneys and spleen. At the doses used, amphotericin B was superior to fluconazole or flucytosine alone in the treatment of C. glabrata infections. Flucytosine reduced the fungal burden in the kidney for only two of four isolates of C. glabrata. The combination of fluconazole and flucytosine was superior to these agents alone in reducing the tissue burden in the kidney for one isolate of C. glabrata. High doses of fluconazole alone produced modest reductions in kidney counts but did not reduce spleen tissue counts. There was poor correlation between in-vitro MICs and in-vivo results.
光滑念珠菌是免疫抑制患者中一种新兴的机会致病菌。光滑念珠菌对许多抗真菌药物耐药,直到最近,针对这种微生物还没有标准的治疗方案。利用用5-氟尿嘧啶免疫抑制的小鼠建立了一个小鼠模型,以评估两性霉素B、氟胞嘧啶、氟康唑及其联合用药治疗静脉内诱导的光滑念珠菌感染的效果。感染后一天开始用氟康唑、氟胞嘧啶、两性霉素B或联合用药进行治疗。治疗5天后,处死小鼠以检测肾脏和脾脏中的真菌数量。在所使用的剂量下,两性霉素B在治疗光滑念珠菌感染方面优于单独使用氟康唑或氟胞嘧啶。氟胞嘧啶仅对四株光滑念珠菌中的两株降低了肾脏中的真菌负荷。氟康唑和氟胞嘧啶联合用药在降低一株光滑念珠菌的肾脏组织负荷方面优于单独使用这些药物。单独使用高剂量氟康唑可适度降低肾脏中的真菌数量,但未降低脾脏组织中的真菌数量。体外最低抑菌浓度(MIC)与体内结果之间的相关性较差。