预防性应用唑类药物对两性霉素B治疗侵袭性真菌感染影响的Meta分析

发布时间：2018-01-14 00:18

本文关键词：预防性应用唑类药物对两性霉素B治疗侵袭性真菌感染影响的Meta分析　出处：《暨南大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的美国传染病学会（2002年）和德国血液与肿瘤协会传染病工作组（2008年）均对化疗后中性粒细胞减少的患者推荐使用唑类药物预防侵袭性真菌感染，患者一旦被诊断为侵袭性真菌感染，则选择多烯类药物进行治疗。但其依据来源于对所有抗真菌药物预防性应用的meta分析，缺乏单独预防性应用唑类药物的meta分析。本研究通过meta分析的方法验证这种先后顺序用药的方法是否有可靠的循证医学依据。方法 1.检索1966年1月至2014年2月的Pubmed、EMBASE、Web of Science、TheCochrane Central Register of Controlled Trials、EBSCO、Ovid、相关期刊论文、中国科技期刊数据库（维普）、万方数字化期刊全文数据库、中国生物医学文献数据库(CBM)等有关对化疗后中性粒细胞减少患者预防性应用唑类药物的临床随机对照试验。以“fluconazole（氟康唑）”、“itraconazole（伊曲康唑）”、“ketoconazole(酮康唑)”、“miconazole(咪康唑)”，“voriconazole(伏立康唑)”，“posaconazole（泊沙康唑）”、“azoles(唑类药物)”和“amphotericinB(两性霉素B)”、“Ambisome,L-amB(两性霉素B脂质体）”、“amphotericin Blipid complex（两性霉素B脂质复合体）”、“amphotericin B colloidal dispersion（两性霉素B胶状分散体）”，“antifungal(抗真菌的)”，“candida(念珠菌属)”、“yeast(酵母菌)”、“mold(霉菌)”、“aspergillus(曲霉菌属)”、“zygomycosis(接合菌病)”、“mycoses（真菌病）”，“neutropenia（中性粒细胞减少症）”、“chemotherapy（化学疗法）”、“cancer(癌症)”、“bone marrowtransplant(骨髓移植)”、“leukemia（白血病）”以及“prophylaxis（预防）”等作为主题词。 2.对符合纳入标准的文献，分别对预防性应用唑类药物组与安慰剂或空白对照组患者的侵袭性真菌感染的死亡专率、全因死亡率的数据进行记录。 3.采用RevMan5.2软件对入选试验进行Meta分析，得出合并后侵袭性真菌感染的死亡专率以及全因死亡率的相对危险度（RR）及其95%的可信区间（CI）。用漏斗图结合Egger法、Begg法检测潜在的发表偏倚。结果共纳入8项随机对照试验（RCT），包含1435名化疗后中性粒细胞减少患者符合入选标准。Meta分析结果显示： 1.侵袭性真菌感染的死亡专率分析预防应用唑类药物组与安慰剂或空白对照组相比，结果显示前期预防性应用唑类药物，后期应用两性霉素B进行治疗，可以降低化疗后中性粒细胞减少患者的侵袭性真菌感染的死亡专率，RR值为0.39（95%CI:0.18~0.86, P=0.21）。 2.全因死亡率的分析预防应用唑类药物组与安慰剂或空白对照组相比，结果显示前期预防性应用唑类药物，后期应用两性霉素B进行治疗，化疗后中性粒细胞减少患者的全因死亡率无显著统计学差异，RR值为1.14（95%CI:0.90~1.45, P=0.95）。结论前期预防性应用唑类药物，后期应用两性霉素B进行治疗，可以降低化疗后中性粒细胞减少患者的侵袭性真菌感染的死亡专率，但对其全因死亡率无明显影响。
[Abstract]:objective
The Infectious Diseases Society of America (2002) and the German Association of infectious diseases and tumor blood group (2008) of neutropenia after chemotherapy in patients with recommended azole prophylaxis of invasive fungal infection patients, once diagnosed with invasive fungal infection, then treatment of polyene drugs. But according to sources for all the antifungal drug preventive application of meta analysis, analysis of the lack of individual preventive use of azole meta. Methods this study through meta analysis and validation of this sequence of therapy is a reliable basis for evidence-based medicine.
Method
1. search from January 1966 to February 2014 Pubmed, EMBASE Web, of Science, TheCochrane Central Register of Controlled Trials, EBSCO, Ovid, Chinese CNKI, China scientific journal database (VIP), Wanfang digital periodical full-text database, China biomedical literature database (CBM) related to post chemotherapy neutropenia with preventive application of azoles in randomized clinical trials. "(Fu Kangzuo fluconazole)," itraconazole "(itraconazole)", "ketoconazole (Tong Kangzuo)," miconazole "(miconazole)", "voriconazole" (voriconazole), posaconazole (Bo Sha Kang Zuo) "," azoles (azoles) "and" amphotericinB (amphotericin B) "," Ambisome, L-amB (liposomal amphotericin B) "," amphotericin Blipid complex (amphotericin B lipid complex), "amphotericin B C" Olloidal dispersion (amphotericin B colloidal dispersion), "antifungal" (antifungal) "," Candida (Candida) "," yeast (yeast), "mold" (mould) "," Aspergillus (aspergillus) "," zygomycosis (zygomycosis) "," mycoses (fungi disease) "," neutropenia (neutropenia), "chemotherapy" (chemotherapy) "," cancer "(cancer), bone marrowtransplant (bone marrow transplant), leukemia (leukemia) and prophylaxis (prevention)" as the theme.
2., according to the inclusion criteria, the death rate and the all-cause mortality data of invasive fungal infection in the prophylactic application group were compared with those in placebo or blank control group.
3. Meta analysis was performed by RevMan5.2 software. The mortality rate and the relative risk (RR) of invasive fungal infection and the confidence interval of 95% (CI) were obtained. The potential publication bias was detected by funnel plot combined with Egger method and Begg method.
Result
A total of 8 randomized controlled trials (RCT), including 1435 patients with neutrophils after chemotherapy, were included in the.Meta analysis.
Analysis of death specificity of 1. invasive fungal infection
The application of azole prophylaxis compared with group with placebo or blank control group showed early prophylactic use of azoles, late application of amphotericin B treatment can reduce post chemotherapy neutropenia patients with invasive fungal infection of the death rate, the value of RR was 0.39 (95%CI:0.18~0.86, P=0.21).
Analysis of 2. total cause mortality
The application of azole prophylaxis compared with group with placebo or blank control group showed early prophylactic use of azoles, late application of amphotericin B treatment after chemotherapy neutropenia in patients with all-cause mortality had no significant difference. The RR value was 1.14 (95%CI,:0.90~1.45, P=0.95) conclusion.
Early prophylactic use of azole drugs and amphotericin B later can reduce the mortality rate of invasive fungal infection in patients with neutrophils after chemotherapy, but it has no significant effect on all-cause mortality.

【学位授予单位】：暨南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R519

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