恶性血液病合并侵袭性真菌感染的早期诊断及治疗研究
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摘要
目的1.应用半乳甘露聚糖(GM)试剂盒检测恶性血液病伴有侵袭性真菌感染(IFI)高危因素患者的血清GM值,评价其对IFI的诊断、疗效预测价值;
2.研究伊曲康唑治疗恶性血液病合并侵袭性真菌感染的疗效;3.建立恶性血液病合并侵袭性真菌感染的早期计算机辅助预测系统。方法1.采集135例IFI高危因素患者的644份血清,应用Elisa方法按GM检测试剂盒检测抗真菌治疗前后GM抗原水平变化。参照IFI分层诊断标准进行评价;2.回顾性分析127例恶性血液病合并侵袭性真菌感染患者应用伊曲康唑治疗的结果;3.应用临床回顾性研究方法研究了南方医院1997年至2007年的恶性血液病合并细菌或真菌感染的病例,采用Binary Logistic回归分析,建立判别模型,利用计算机编程技术开发辅助诊断系统软件。结果1.GM阳性患者52例,其中在确诊组5例、临床诊断组9例、拟诊组32例、不符合IFI组6例,阳性率分别为71.4%、64.3%、43.8%和14.6%;本次GM试验灵敏度0.67,特异度0.85,阳性预测值0.70,阴性预测值0.83;GM阳性患者选择覆盖曲霉菌的抗生素治疗的有效率65.7%,治疗后平均GM值从由2.02±0.62降至0.63±0.17(t=15.651,P=0.000),而用氟康唑治疗的有效率为27.3%,显著低于非氟康唑治疗组。GM阴性患者采用氟康唑或两性霉素B、伊曲康唑药物间疗效无明显差别,治疗后平均GM值从0.38±0.22降至0.33±0.21(t=1.609,P=0.112);2.伊曲康唑临床总有效率47.2%(60/127);在确诊、临床诊断和拟诊组病例的有效率分别为66.7%(16/24)、51.5%(33/64)、28.2%(11/39);拟诊组低于确诊组(x~2=8.974,P=0.004);拟诊组低于临床诊断组(x~2=5.403,P=0.025),副作用轻微。伊曲康唑对检出菌株,接受移植、使用激素及负荷量给药的患者有效率高于对照组(x~2=25.321,P=0.000;x~2=13.023,P=0.000;x~2=16.552,P=0.000;x~2=13.119,P=0.000);3.共收集到符合条件的病例304例,其中真菌感染194例,细菌感染110例,建立了回归方程,方程的分类能力为95.4%,有效性检验P=0.000,据此开发了计算机辅助早期诊断系统,应用于临床,符合率为92.3%。结论1.GM试验灵敏度中等、特异性较高,高危患者检测阳性应立即抗曲霉菌治疗,动态检测GM值变化可有效判断治疗效果;2.伊曲康唑对治疗恶性血液病合并侵袭性真菌感染有良好的疗效,且药物安全可靠;3.计算机辅助恶性血液病合并侵袭性真菌感染的早期诊断系统具有一定的临床参考价值。
Objective 1.To evaluate the diagnosis and prediction value of serum galactomannan(GM) Platelia Aspergillus Kit in malignant hematologic disease complicated with invasive fungal infections(IFI).2.To investigate the efficacy of intravenous administration of itraconazole on invasion fungal infections in patients with hematologic malignancies.3.To establish computer aided early diagnosis system of malignant hematologic disease complicated with invasive fungal infections(IFI). Methods 1.644 serum samples obtained from 135 high risk patients were collected, and ELISA assay was used to analyse the change of GM antigen.2.Using itraconazole to treat 127 patients with hematologic malignancies affiliating invasive fungal infections,retrospective analyzing the therapeutic result.3.304 cases obtained from 1997 to 2007 in Nanfang hospital,and adopt binary logistic analysis to establish regression model.Computer program was built base on this results.Results 1.According to the classification criterion of IFI,the GM positive patient in proven, probable,possible and improbable IFI groups were 5,9,32,and 6,respectively;And the positive rate in every groups were respectively 71.4%,64.3%,43.8%and 14.6%. The sensitivity and specificity of the galactomannan ELISA assay were 0.67 and 0.85 and the positive and negative predictive values were 0.70 and 0.83 respectively.The therapic effect of amphotericin B or itraconazole to GM positive patient is superior than that of Fluconazol,but which was not founded in GM negative patients.After antithngal therapy,,the average OD values of the GM positive patients decreased from 2.02±0.62 to 0.63±0.17(t=15.651,P=0.000),But in GM negative patients,the number were 0.38±0.22 and 0.33±0.21(t=1.609,P=0.112).2.The total efficacy rate was 47.2%(60/127).The efficacy rates of the patients with confirmed diagnosis,with clinical diagnosis and with recommended diagnosis were 66.7%(16/24)、51.5%(33/64),28.2%(11/39) respective.The efficacy rate of recommended diagnosis group was obviously lower than confirmed diagnosis group(x~2=8.974,P=0.004) and lower than clinical diagnosis group(x~2=5.403,P=0.025).The adverse side effect of itraconazole was little.The efficacy rates in groups which were checked out fungus, accepted transplantation,used hormone and treated with loading dose of itraconazole are higher than control group(x~2=25.321,P=0.000;x~2=13.023,P=0.000; x~2=16.552,P=0.000;x~2=13.119,P=0.000).3.The regression model's Classification is 95.4%,and the model coefficients is 0.000.The computer program was used in Nanfang hospital,and the validity is 92.3%.Conclusion 1.The sensitivity of galactomannan ELISA assay was moderate,but its specificity was high.The patient with high risk factor whose GM test is positive should begin antifungle therapy immediately,but the negative result can not exclusive IFI.The change of GM values can be as a reliable index to predict the antifungle effect.2.Itraconazole can treated patients with hematologic malignancies affiliating invasive fungal infections effectually and safety.3.Computer aided system is effective to help to early diagnose the malignant hematologic disease complicated with invasive fungal infections.
2.研究伊曲康唑治疗恶性血液病合并侵袭性真菌感染的疗效;3.建立恶性血液病合并侵袭性真菌感染的早期计算机辅助预测系统。方法1.采集135例IFI高危因素患者的644份血清,应用Elisa方法按GM检测试剂盒检测抗真菌治疗前后GM抗原水平变化。参照IFI分层诊断标准进行评价;2.回顾性分析127例恶性血液病合并侵袭性真菌感染患者应用伊曲康唑治疗的结果;3.应用临床回顾性研究方法研究了南方医院1997年至2007年的恶性血液病合并细菌或真菌感染的病例,采用Binary Logistic回归分析,建立判别模型,利用计算机编程技术开发辅助诊断系统软件。结果1.GM阳性患者52例,其中在确诊组5例、临床诊断组9例、拟诊组32例、不符合IFI组6例,阳性率分别为71.4%、64.3%、43.8%和14.6%;本次GM试验灵敏度0.67,特异度0.85,阳性预测值0.70,阴性预测值0.83;GM阳性患者选择覆盖曲霉菌的抗生素治疗的有效率65.7%,治疗后平均GM值从由2.02±0.62降至0.63±0.17(t=15.651,P=0.000),而用氟康唑治疗的有效率为27.3%,显著低于非氟康唑治疗组。GM阴性患者采用氟康唑或两性霉素B、伊曲康唑药物间疗效无明显差别,治疗后平均GM值从0.38±0.22降至0.33±0.21(t=1.609,P=0.112);2.伊曲康唑临床总有效率47.2%(60/127);在确诊、临床诊断和拟诊组病例的有效率分别为66.7%(16/24)、51.5%(33/64)、28.2%(11/39);拟诊组低于确诊组(x~2=8.974,P=0.004);拟诊组低于临床诊断组(x~2=5.403,P=0.025),副作用轻微。伊曲康唑对检出菌株,接受移植、使用激素及负荷量给药的患者有效率高于对照组(x~2=25.321,P=0.000;x~2=13.023,P=0.000;x~2=16.552,P=0.000;x~2=13.119,P=0.000);3.共收集到符合条件的病例304例,其中真菌感染194例,细菌感染110例,建立了回归方程,方程的分类能力为95.4%,有效性检验P=0.000,据此开发了计算机辅助早期诊断系统,应用于临床,符合率为92.3%。结论1.GM试验灵敏度中等、特异性较高,高危患者检测阳性应立即抗曲霉菌治疗,动态检测GM值变化可有效判断治疗效果;2.伊曲康唑对治疗恶性血液病合并侵袭性真菌感染有良好的疗效,且药物安全可靠;3.计算机辅助恶性血液病合并侵袭性真菌感染的早期诊断系统具有一定的临床参考价值。
Objective 1.To evaluate the diagnosis and prediction value of serum galactomannan(GM) Platelia Aspergillus Kit in malignant hematologic disease complicated with invasive fungal infections(IFI).2.To investigate the efficacy of intravenous administration of itraconazole on invasion fungal infections in patients with hematologic malignancies.3.To establish computer aided early diagnosis system of malignant hematologic disease complicated with invasive fungal infections(IFI). Methods 1.644 serum samples obtained from 135 high risk patients were collected, and ELISA assay was used to analyse the change of GM antigen.2.Using itraconazole to treat 127 patients with hematologic malignancies affiliating invasive fungal infections,retrospective analyzing the therapeutic result.3.304 cases obtained from 1997 to 2007 in Nanfang hospital,and adopt binary logistic analysis to establish regression model.Computer program was built base on this results.Results 1.According to the classification criterion of IFI,the GM positive patient in proven, probable,possible and improbable IFI groups were 5,9,32,and 6,respectively;And the positive rate in every groups were respectively 71.4%,64.3%,43.8%and 14.6%. The sensitivity and specificity of the galactomannan ELISA assay were 0.67 and 0.85 and the positive and negative predictive values were 0.70 and 0.83 respectively.The therapic effect of amphotericin B or itraconazole to GM positive patient is superior than that of Fluconazol,but which was not founded in GM negative patients.After antithngal therapy,,the average OD values of the GM positive patients decreased from 2.02±0.62 to 0.63±0.17(t=15.651,P=0.000),But in GM negative patients,the number were 0.38±0.22 and 0.33±0.21(t=1.609,P=0.112).2.The total efficacy rate was 47.2%(60/127).The efficacy rates of the patients with confirmed diagnosis,with clinical diagnosis and with recommended diagnosis were 66.7%(16/24)、51.5%(33/64),28.2%(11/39) respective.The efficacy rate of recommended diagnosis group was obviously lower than confirmed diagnosis group(x~2=8.974,P=0.004) and lower than clinical diagnosis group(x~2=5.403,P=0.025).The adverse side effect of itraconazole was little.The efficacy rates in groups which were checked out fungus, accepted transplantation,used hormone and treated with loading dose of itraconazole are higher than control group(x~2=25.321,P=0.000;x~2=13.023,P=0.000; x~2=16.552,P=0.000;x~2=13.119,P=0.000).3.The regression model's Classification is 95.4%,and the model coefficients is 0.000.The computer program was used in Nanfang hospital,and the validity is 92.3%.Conclusion 1.The sensitivity of galactomannan ELISA assay was moderate,but its specificity was high.The patient with high risk factor whose GM test is positive should begin antifungle therapy immediately,but the negative result can not exclusive IFI.The change of GM values can be as a reliable index to predict the antifungle effect.2.Itraconazole can treated patients with hematologic malignancies affiliating invasive fungal infections effectually and safety.3.Computer aided system is effective to help to early diagnose the malignant hematologic disease complicated with invasive fungal infections.
引文
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