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中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (03) : 262 -267. doi: 10.3877/cma.j.issn.1673-5250.2019.03.005

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论著

卡泊芬净治疗儿童血液病合并侵袭性真菌病的临床评价
邱坤银1, 廖雄宇1, 郭淑仪1, 吴若豪1, 黄科1, 黎阳1, 徐宏贵1, 方建培1, 周敦华1,()   
  1. 1. 中山大学孙逸仙纪念医院儿科,广州 510120
  • 收稿日期:2018-10-29 修回日期:2019-04-17 出版日期:2019-06-01
  • 通信作者: 周敦华

Clinical evaluation of caspofungin in treatment of invasive fungal disease in children with hematological diseases

Kunyin Qiu1, Xiongyu Liao1, Shuyi Guo1, Ruohao Wu1, Ke Huang1, Yang Li1, Honggui Xu1, Jianpei Fang1, Dunhua Zhou1,()   

  1. 1. Department of Pediatrics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
  • Received:2018-10-29 Revised:2019-04-17 Published:2019-06-01
  • Corresponding author: Dunhua Zhou
  • About author:
    Corresponding author: Zhou Dunhua, Email:
  • Supported by:
    Special Fund Project of Guangdong Science and Technology Development(2017A020215086)
引用本文:

邱坤银, 廖雄宇, 郭淑仪, 吴若豪, 黄科, 黎阳, 徐宏贵, 方建培, 周敦华. 卡泊芬净治疗儿童血液病合并侵袭性真菌病的临床评价[J/OL]. 中华妇幼临床医学杂志(电子版), 2019, 15(03): 262-267.

Kunyin Qiu, Xiongyu Liao, Shuyi Guo, Ruohao Wu, Ke Huang, Yang Li, Honggui Xu, Jianpei Fang, Dunhua Zhou. Clinical evaluation of caspofungin in treatment of invasive fungal disease in children with hematological diseases[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(03): 262-267.

目的

探讨卡泊芬净治疗儿童血液病合并侵袭性真菌病(IFD)的疗效及安全性。

方法

选择2013年6月至2016年6月,于中山大学孙逸仙纪念医院儿科血液肿瘤病区诊断为合并IFD,并且接受卡泊芬净治疗的57例血液病患儿为研究对象。回顾性分析其临床病例资料。采用χ2检验及t检验,对本组血液病合并不同诊断级别IFD患儿的卡泊芬净治疗有效率、各诊断级别IFD卡泊芬净一线及二线治疗的有效率及不同诊断级别IFD的血液病患儿卡泊芬净治疗后12周生存率,卡泊芬净治疗有效和无效患儿的疗程,以及不同中性粒细胞缺乏时间患儿的卡泊芬净治疗有效率,进行统计学比较,并评价卡泊芬净治疗血液病合并IFD的安全性。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并且与所有患儿监护人均签署卡泊芬净使用知情同意书。

结果

①本组血液病患儿中,91.2%(52/57)为单一部位合并IFD,以肺部最为常见(78.9%,45/57);确诊IFD为5例(8.8%),临床诊断IFD为38例(66.7%),拟诊IFD为14例(24.5%)。②卡泊芬净治疗57例血液病合并IFD患儿的总有效率为86.0%(49/57)。临床诊断和拟诊IFD患儿的卡泊芬净治疗有效率为90.4%(47/52),高于确诊IFD患儿的40.0%(2/5),并且差异有统计学意义(χ2=9.597,P=0.001)。③确诊和临床诊断IFD患儿的卡泊芬净一线治疗有效率为96.7%(29/30),显著高于二线治疗的76.9%(10/13),并且差异有统计学意义(χ2=4.190,P=0.041)。拟诊IFD患儿卡泊芬净一线治疗有效率为90.0%(9/10),亦显著高于二线治疗的25.0%(1/4),并且差异有统计学意义(χ2=5.915,P=0.015)。④确诊、临床诊断及拟诊IFD的血液病患儿卡泊芬净治疗后12周的生存率比较,差异无统计学意义(P>0.05)。⑤卡泊芬净治疗有效患儿的疗程为(16±7) d,显著长于治疗无效患儿的(8±6) d,并且差异有统计学意义(t=3.730,P=0.032)。⑥卡泊芬净对中性粒细胞缺乏时间≥14 d患儿的治疗有效率为66.6%,显著低于中性粒细胞缺乏时间<14 d患儿的92.9%,并且差异有统计学意义(χ2=6.284,P=0.012)。⑦本组患儿无一例发生与使用卡泊芬净相关的不良反应。

结论

卡泊芬净治疗儿童血液病合并IFD疗效确切,患儿中性粒细胞缺乏可影响其疗效。该药无明显药物不良反应,推荐应用于血液病合并IFD儿童一线抗真菌治疗,治疗疗程建议>14 d。

Objective

To investigate the efficacy and safety of caspofungin in treatment of children with hematological diseases complicated with invasive fungal disease (IFD).

Methods

From June 2013 to June 2016, a total of 57 children with hematological diseases who were diagnosed as complicated with IFD, and treated by caspofungin in the department of Pediatric Hematology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, were chosen as research objects. Their clinical case data were analyzed retrospectively. Chi-square test and t test were applied to compare treatment effective rates of caspofungin between hematological disease children with different diagnostic grades of IFD, treatment effective rates of caspofungin between the first-line and the second-line treatment in each diagnostic grades of IFD, the survival rates of hematological disease children with different diagnostic grades of IFD after 12 weeks of caspofungin treatment, also the courses of caspofungin treatment between hematological disease children with effective and ineffective treatment, as well as treatment effective rates of caspofungin between hematological disease children with different duration of neutropenia. And the safety of caspofungin in treatment of children with hematological diseases complicated with IFD was also evaluated. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013, and all guardians of these children signed the informed consent forms for treatment by caspofungin.

Results

①Among hematological disease children of this study, 91.2%(52/57) were single site infected with fungi, and pulmonary infection by fungi was the most common (78.9%, 45/57). Among them, 5 cases (8.8%) were proven IFD, 38 cases (66.7%) were probable IFD, and 14 cases (24.5%) were possible IFD. ②The total treatment effective rate of caspofungin in 57 hematological disease children was 86.0%(49/57). Treatment effective rate of caspofungin in probable and possible IFD children were 90.4%(47/52), which were higher than that of 40.0%(2/5) in proven IFD children, and the difference was statistically significant (χ2=9.597, P=0.001). ③Treatment effective rate of caspofungin as the first-line treatment in hematological disease children with proven and probable IFD was 96.7%(29/30), which was higher than that of 76.9%(10/13) in caspofungin as the second-line treatment, and the difference was statistically significant (χ2=4.190, P=0.041). The effective rate of caspofungin as the first-line treatment in hematological disease children with possible IFD was 90.0%(9/10), which was higher than that of 25.0%(1/4) in caspofungin as the second-line treatment, and the difference was statistically significant (χ2=5.915, P=0.015). ④There was no significant difference among proven, probable and possible IFD in the survival rates after 12 weeks of treatment by caspofungin (P>0.05). ⑤The course of treatment in hematological disease children with effective treatment of caspofungin was (16±7) d, which was longer than that in hematological disease children with ineffective treatment (8±6) d, and the difference was statistically significant (t=3.730, P=0.032). ⑥The effective rate of caspofungin between hematological disease children with duration of neutropenia≥14 d was 66.6%, which was significantly lower than that of hematological disease children with duration of neutropenia <14 d (92.9%), and the difference was statistically significant (χ2=6.284, P=0.012). ⑦None of hematological disease children occurred adverse reactions related to the treatment by caspofungin.

Conclusions

Caspofungin has significant curative effect in treatment of hematological diseases complicated with IFD in children, and neutropenia might affect its effect. Caspofungin has no obvious adverse reactions and it can be recommended for the first-line antifungal therapy in hematological disease children complicated with IFD, and its course of treatment would be more than 14 d.

表1 确诊和临床诊断侵袭性真菌病的血液病患儿中,卡泊芬净一线及二线治疗的疗效评估结果[例数(%)]
表2 拟诊侵袭性真菌病的血液病患儿中,卡泊芬净一线及二线治疗的疗效评判指标评估结果[例数(%)]
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