两性霉素B与氟康唑序贯、联合治疗非艾滋病相关隐球菌性脑膜炎

Efficacy of sequential or combined amphotericin B and fluconazole therapy in non-acquiredimmunodeficiency syndrome-related cryptecoccal meningitis

目的探讨在联合5-氟胞嘧啶的基础上，两性霉素B与氟康唑序贯、联合治疗非AIDS相关隐球菌性脑膜炎的疗效。方法将117例非AIDS相关隐球菌性脑膜炎患者根据治疗方法分为5组，在使用5-氟胞嘧啶的基础上，应用两性霉素B组38例、氟康唑组25例、先氟康唑后两性霉素B组18例、先两性霉素B后氟康唑组15例及联合组21例，比较各组治疗后脑脊液中各指标变化。统计学处理采用t检验，单因素方差分析、多个独立样本检验和卡方检验。结果两性霉素B组、氟康唑组、先氟康唑后两性霉素B序贯组、先两性霉素B后氟康唑序贯组及联合组治疗后的颅内压分别为（208．6±75．1）、（191．5±94．5）、（185．0±76．3）、（201．9±69．7）和（223．1±89．3）mmH2O（1mmH2O=0．0098kPa），差异无统计学意义（F=0．611，P=0．656）；脑脊液隐球菌中位数分别为0、10、0、3和0个／mL，差异无统计学意义（X^2=7．638，P=0．090）；脑脊液蛋白水平分别为0．55、0．69、0．67、0．53和0．96g／L，差异无统计学意义（F=7．063，P=0．133）；治愈率分别为55．3％（21／38）、32．0％（8／25）、9／18、6／15和47．6％（10／Z1），差异无统计学意义（X^2=3．638，P=0．457）；加重或死亡的比率分别为28．9％（11／38）、44．4％（11／25）、5／18、4／15和23．8％（5／21），差异无统计学意义（X^2=2．785，P=0．604）。结论两性霉素B与氟康唑及两者序贯或联合治疗对隐球菌性脑膜炎均有较好的疗效。

Objective To explore the efficacy of sequential or combined amphotericin B （AraB） and fluconazole （FCZ） therapy on a 5-flucytosine-based regimen in non-acquired immunodeficiency syndrome （AIDS）-related cryptococcal meningitis. Methods A tatal of 117 cases of non-AIDS-related cryptococcal meningitis treated with 5-flurocytosine-based regimens were retrospectively divided into five groups： AmBgroup （n=38）, FCZ group （n=25）, FCZ and AraB sequential group （n=18）, AraB and FCZ sequential group （n=15）, AraB and FCZ combination group （n=21）. The number in cerebrospinal fluid （CSF） of the five groups were compared. Statistical analyses included t test, one- way analysis of variance, K independent samples test and chi-square test. Results Intracranial pressure of AraB group, FCZ group, FCZ and AraB sequential group, AraB and FCZ sequential group,AraB and FCZ combination group were （208. 6±75. 1）, （191. 5±94. 5）, （185.0±76.3）,（201. 9±69. 7） and （223. 1±89. 3） mm H2O （1 mm H2O=0.0098 kPa）, respectively, and the differences were not statistically significant （F= 0. 611, P=0. 656）. Median cryptococcus counts in CSF of the five groups were 0, 10, 0, 3 and 0/mL, respectively, with no statistical significance （X^2= 7. 638, P=0. 090）. CSF protein levels of the five groups were 0.55, 0.69, 0.67, 0.53 and 0.96 g/L, respectively, with no significant differences among groups （F=7.063, P=0.133）. The cure rates of the five groups were 55.3% （21/38）, 32.0% （8/25）, 9/18, 6/15 and 47.6% （10/21）, respectively; progression rates or mortality of the five groups were 28.9%（11/38）, 44.4% （11/25）, 5/18, 4/15 and 23.8%（5/21）, respectively; and the differences among cure rates （X^2=3.638, P=0.457） and progression rates or mortality （X^2= 2.785, P = 0. 604） were not statistically significant. Conclusion FCZ or AmB alone, sequential or combined therapy were all effective in the treatment of cryptococcal meningitis.