Allendoerfer R, Marquis A J, Rinaldi M G, Graybill J R
Department of Medicine, University of Texas Health Science Center, San Antonio.
Antimicrob Agents Chemother. 1991 Apr;35(4):726-9. doi: 10.1128/AAC.35.4.726.
To assess the possible beneficial effects of combined therapy (fluconazole and flucytosine) in the treatment of cryptococcal meningitis in the immunocompromised host, we compared therapy with fluconazole and flucytosine, individually and combined, in the experimental murine model. BALB/c athymic (nu/nu) mice were infected intracerebrally with 150 to 300 CFU of Cryptococcus neoformans. In mortality studies, treatment was initiated 24 h postinfection and continued for 10 to 14 days with either fluconazole (1 to 15 mg/kg of body weight per day), flucytosine (60 to 120 mg/kg/8 h), both drugs, or 0.3% Noble agar (control). Combined therapy delayed mortality significantly when compared with controls and single-drug regimens. This was observed over a broad range of doses. Quantitative determinations of CFU in brain tissue demonstrated a significantly lower burden of C. neoformans in mice receiving combined therapy. The results indicate that combined therapy with fluconazole and flucytosine is superior to single-drug therapy.
为评估联合治疗（氟康唑和氟胞嘧啶）在免疫功能低下宿主中治疗新型隐球菌性脑膜炎的潜在有益效果，我们在实验性小鼠模型中比较了氟康唑和氟胞嘧啶单独及联合治疗的效果。将150至300 CFU新型隐球菌脑内接种于BALB/c无胸腺（nu/nu）小鼠。在死亡率研究中，感染后24小时开始治疗，用氟康唑（每日1至15毫克/千克体重）、氟胞嘧啶（每8小时60至120毫克/千克）、两种药物联合或0.3%诺布尔琼脂（对照）持续治疗10至14天。与对照组和单药治疗方案相比，联合治疗显著延迟了死亡率。在广泛的剂量范围内均观察到这一现象。对脑组织中CFU的定量测定表明，接受联合治疗的小鼠新型隐球菌负荷显著降低。结果表明，氟康唑和氟胞嘧啶联合治疗优于单药治疗。
