Kartalija M, Kaye K, Tureen J H, Liu Q, Täuber M G, Elliott B R, Sande M A
Infectious Diseases Laboratory, San Francisco General Hospital, CA 94143-0811, USA.
J Infect Dis. 1996 May;173(5):1216-21. doi: 10.1093/infdis/173.5.1216.
Fluconazole is effective in the therapy of cryptococcal meningitis in patients with AIDS. The optimal dosage of fluconazole and the impact of combination with flucytosine are not known. In this study, rabbits with experimental cryptococcal meningitis were given fluconazole at low, intermediate, or high dose or in combination with a low or intermediate dose of flucytosine. Serial cerebrospinal fluid (CSF) examinations showed that all three doses of fluconazole and low-dose fluconazole in combination with intermediate-dose flucytosine were effective in reducing CSF cryptococcal titer, lactate, white blood cell count, and cryptococcal antigen (CRAG) titers. The intermediate and high doses of fluconazole reduced CSF fungal (P < .05) and CRAG (P < .001) titers earlier than low-dose fluconazole alone or in combination with flucytosine. Only the highest dose of fluconazole reduced brain edema after 7 days. In this model of cryptococcal meningitis, there was evidence of a dose response with fluconazole but no in vivo synergism with flucytosine.
氟康唑对艾滋病患者的隐球菌性脑膜炎治疗有效。氟康唑的最佳剂量以及与氟胞嘧啶联合使用的效果尚不清楚。在本研究中，给患有实验性隐球菌性脑膜炎的兔子分别给予低、中、高剂量的氟康唑，或与低剂量或中剂量的氟胞嘧啶联合使用。连续的脑脊液（CSF）检查表明，所有三种剂量的氟康唑以及低剂量氟康唑与中剂量氟胞嘧啶联合使用均能有效降低脑脊液中的隐球菌滴度、乳酸水平、白细胞计数和隐球菌抗原（CRAG）滴度。氟康唑的中、高剂量比单独使用低剂量氟康唑或与氟胞嘧啶联合使用能更早地降低脑脊液真菌（P <.05）和CRAG（P <.001）滴度。仅最高剂量的氟康唑在7天后可减轻脑水肿。在这个隐球菌性脑膜炎模型中，有证据表明氟康唑存在剂量反应，但与氟胞嘧啶无体内协同作用。
