伏立康唑治疗血液病侵袭性真菌感染93例报道

Clinical analysis of voriconazole in the treatment of invasive fungal infections of the patients with blood diseases

目的观察伏立康唑治疗血液病患者并发侵袭性真菌感染(IFI)的临床疗效及安全性。方法回顾分析2006—2008年天津医科大学总医院住院的93例血液病患者并发IFI的临床表现及使用伏立康唑的疗效和不良反应。结果93例IFI患者中确诊4例(4.3%)、临床诊断76例(81.7%)、拟诊13例(14.0%)。感染部位以肺部为主(87例,占93.5%),鼻腔感染2例(2.2%),血流感染2例(2.2%)、中枢神经系统和肝脏感染各1例。G试验阳性者74例(80.0%)。22例有真菌学依据,其中念珠菌12例(54.5%),曲霉菌7例(32.0%),隐球菌1例(4.5%),其他2例(9.0%)。出现影像学改变者71例(76.3%),以磨玻璃影最多(44例),其次为多发斑片状阴影(13例),不规则多发结节高密度影5例,有晕轮征者4例,有空洞形成者2例,其他改变3例。伏立康唑静脉用药时间平均14d,序贯伏立康唑口服平均20d,总疗程约34d。93例IFI患者治疗有效71例(76.4%),疗效不佳11例(11.8%),死亡11例(11.8%)。其中拟诊组有效率84.6%,临床诊断组有效率77.6%,两者之间差异无统计学意义(P=0.267)。确诊组治疗有效率25%,疗效明显低于前两组(P<0.05)。影响疗效的主要因素有中性粒细胞绝对值、不同菌属、合并细菌感染、G试验值。中性粒细胞绝对值小于0.2×109/L者疗效明显低于大于0.2×109/L者(56.3%对86.9%,P<0.01)、曲霉菌感染者疗效明显差于念珠菌感染者(83.3%对28.6%,P<0.05)、合并革兰阴性杆菌血流感染及嗜麦芽窄食单胞菌感染患者疗效明显低于无此并发症的患者(42.1%对85.1%,P<0.001)、治疗后G试验未降至正常者疗效明显低于G试验降至正常者(38.1%对94.3%,P<0.001)。治疗相关不良反应主要为肝脏转氨酶的升高(50例,占53.8%),以γ-谷氨酰转肽酶(GGT)升高为主(41例,44.1%),其次为一过性的视觉障碍,均不需要终止伏立康唑的治疗。结论伏立康唑能安全、有效地控制血液病患者并发的IFI。

Objective To investigate the efficacy and adverse effects of voriconazole in the treatment of invasive fungal infections （IFI）of the patients with blood diseases. Methods The clinical manifestations and treatment of 93 1FI patients with blood diseases occurring during 2006 to 2008 were retrospectively analyzed. Results Of the 93 IF/cases with blood diseases,4（4. 3% ）were proven,76（81.7% ）probable and 13（ 14. 0% ）possible. 87（93.5% ）cases were with lower respiratory tract infection,2（2. 2% ）with nasal cavity infection,2（2. 2% ）with Candida bloodstream infection, 1 with central nerve system infection and another 1 with fungus infection of liver. The G test was positive in 74 cases（80. 0% ）. Mycological evidence was found in 22 cases,including Candida（ 12 cases,54. 0% ）, aspergillus （7 cases, 32.0% ）, cryptococcus （ 1 case ,4. 5 % ） and others （2 cases ,9. 0% ）. Computed tomography imaging findings were positive in 71 cases （76. 3% ）, including ground-glass opacity（44 cases）,multiple patchy densities （ 13 cases）, irregular muhifocal node high density shadow （5 cases ）, air-crescent sign （4 cases）, cavity（ 3 cases）and others （3 cases ）. The median time of voriconazole treatment intravenously and orally was 14 and 20 days respectively. 71 IFI （76.4%）cases showed responses to voriconazole, 11 （ 11.8 % ）had no improvement, and another 11 （ 11.8% ） died. The efficacy on possible cases was not significantly different from that on probable cases（ P = 0. 267 ）, but the efficacy on proven cases was significantly lower than that on probable and possible eases（ P = 0. 034 ）. The neutrophile count less than 0. 2 × 10^9/L（ P = 0. 004 ）, invasive fungal Aspergillo- sis, IFI with Gram-Negative bacillus sepsis or Stenotrophomonas malto-philia infections and positive of G test after antifungal treatment predicted poor prognosis （P 〈 0. 001 ）. Adverse effects associated with voriconazole were significant transaminitis（50 cases ,53.4% ）and transient ocular toxicity. It was not necessary to stop voriconazole for reducing those adverse effects. Conclusion Voriconazole is effective and safe in the treatment of IFI cases with blood diseases.