Abstract：
OBJECTIVE: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood.
METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year.
RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality.
CONCLUSIONS: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.
METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year.
RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality.
CONCLUSIONS: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.
摘要：
背景：对HIV阴性患者中隐球菌性脑膜炎（CM）的抗真菌易感性与死亡率之间的关系了解甚少。
方法：我们对200例HIV阴性CM患者的1年随访进行了回顾性分析，这些患者接受了新生隐球菌的初始脑脊液（CSF）培养。根据最小抑制浓度(MIC)的截止值,分为两组五种抗真菌药：两性霉素B（AmB），≤0.5µg/ml，>0.5µg/ml；5-氟胞嘧啶（5-FC），≤4微克/毫升，>4微克/毫升；氟康唑(FLU)，≤4微克/毫升，>4µg/ml；伊曲康唑（ITR），≤0.125微克/毫升，>0.125µg/ml；伏立康唑（VOR），<0.25微克/毫升，≥0.25微克/毫升。进行比较以分析临床特征，实验室,1年内不同预后结局下的改良Rankin量表（mRS）评分和CSF结果。
结果：所有新生隐球菌分离株对AmB和VOR敏感，他们中的大多数对5-FC和FLU敏感(95.5%和90.5%，分别），而其中只有55.0%对ITR易感。ITR和VOR的MIC与基线mRS评分显著相关。新生隐球菌菌株的全因死亡率与MIC没有显着相关。实际抗真菌剂的组合和两组抗真菌剂的MIC值对全因死亡率没有显着影响。
结论：大多数新生隐球菌分离株对AmB敏感，VOR,5-FC,和FLU。因为死亡人数少,我们无法评论MIC是否与HIV阴性患者的CM死亡率相关.
方法：我们对200例HIV阴性CM患者的1年随访进行了回顾性分析，这些患者接受了新生隐球菌的初始脑脊液（CSF）培养。根据最小抑制浓度(MIC)的截止值,分为两组五种抗真菌药：两性霉素B（AmB），≤0.5µg/ml，>0.5µg/ml；5-氟胞嘧啶（5-FC），≤4微克/毫升，>4微克/毫升；氟康唑(FLU)，≤4微克/毫升，>4µg/ml；伊曲康唑（ITR），≤0.125微克/毫升，>0.125µg/ml；伏立康唑（VOR），<0.25微克/毫升，≥0.25微克/毫升。进行比较以分析临床特征，实验室,1年内不同预后结局下的改良Rankin量表（mRS）评分和CSF结果。
结果：所有新生隐球菌分离株对AmB和VOR敏感，他们中的大多数对5-FC和FLU敏感(95.5%和90.5%，分别），而其中只有55.0%对ITR易感。ITR和VOR的MIC与基线mRS评分显著相关。新生隐球菌菌株的全因死亡率与MIC没有显着相关。实际抗真菌剂的组合和两组抗真菌剂的MIC值对全因死亡率没有显着影响。
结论：大多数新生隐球菌分离株对AmB敏感，VOR,5-FC,和FLU。因为死亡人数少,我们无法评论MIC是否与HIV阴性患者的CM死亡率相关.
