儿童急性白血病合并真菌血症相关危险因素的病例对照研究

目的 探讨急性白血病患儿合并真菌血症的危险因素。方法 以首都医科大学附属北京儿童医院血液肿瘤中心2002年1月至2014年6月收治的急性白血病且2次血培养真菌阳性的病例为真菌血症组；以同期住院、同性别、既往无真菌感染、且未发生真菌血症的急性白血病患儿为对照组，样本量对照组与真菌血症组1∶1。采集年龄、白血病状态（缓解与否）、复发情况、住院时间、是否应用含激素的化疗方案、中性粒细胞缺乏（＜0.5×109·L-1）及其持续时间、中心静脉置管、广谱抗生素应用和合并败血症等因素，行真菌血症组和对照组单因素和多因素分析。结果 真菌血症组纳入48例，男32例，应用化疗药物累计中位时间98（3~300） d，中位年龄5.6（1.4~13.8）岁；对照组纳入96例，应用化疗药物累计中位时间201（4~1 080）d，男64例，中位年龄6.7（1~15）岁。①真菌血症组48例均有发热，中位发热时间8.6（1~42）d。住院至出现真菌血症的中位时间17.6（1~115）d；既往有真菌感染5例（10.4%），合并脏器功能衰竭7例（14.6%）；10例（20.8%）合并细菌败血症；死亡或临终放弃治疗11例（22.9%）。③血培养结果示，近平滑念珠菌和热带念珠菌各17例（35.4%），白色念珠菌8例（16.7%），季也蒙念珠菌2例（4.2%），光滑念珠菌、青霉菌、镰刀菌属和阿萨希毛孢子菌各1例（2.1%）。④单因素分析显示，白血病未缓解、中性粒细胞缺乏及其持续时间＞7 d、应用广谱抗生素、静脉应用抗生素>7 d和合并败血症是急性白血病合并真菌血症的危险因素；多因素Logsitic分析显示，应用广谱抗生素是急性白血病合并真菌血症的独立危险因素，OR=28.3(95%CI: 5.9~136.2)。结论 念珠菌属为急性白血病合并真菌血症的主要病原体，非白色念珠菌占优势。应用广谱抗生素是急性白血病合并真菌血症的独立危险因素。

Risk factors for pediatric acute leukemia complicated with fungemia:a case-control study

Objective To investigated the risk factors for pediatric acute leukemia complicated with fungemia. Methods Pediatric acute leukemia patients with blood culture fungus positive from 01/2002 to 06/2014 were taken as fungemia group,from Oncology Center of Beijing Children's Hospital affiliated to Capital Medical University;While the control group included the patients with same in hospital time,same sex,without fungal infection history and fungemia happened. The sample size was 1:2 for fungemia group to control group. The data of age,morbid state( remission or not),relapse situation,in hospital time,using hormonal chemotherapy regimens or not,neutropenia time and degree,central venous indwelling catheter,using broad-spectrum antibiotics and accompanied with septicemia were collected. Single factor and multiple-factor analyses were used to investigate the risk factors for pediatric acute leukemia complicated with fungemia. Results There were 48 cases in fungemia group,male patients 38,median time of using chemotherapeutics was 98(3-300)d,median age was 5. 6(1. 4-13. 8)years. There were 96 cases in control group,male patients 64,median time of using chemotherapeutics was 201(4 -1 080)d,median age was 6. 7(1 -15) years. ① All 48 cases had fever in fungemia group,median time of fever duration time was 8. 6(1 -42)d. Median time from admitting to hospital to fungemia was 17. 6(1 ~115)d;② 5 cases were with fungal infection history(10. 4%);7 cases were complicated with organ function failur(14. 6%);10 cases with bacteria septicemia(20. 8%);11 cases died or giving up treatment (22. 9%).③ Cultivating result showed that in 17 cases both candida parapsilosis and tropicalis(35. 4%)were positive,in 8 cases candida albicans(16. 7%)positive,in 2 cases season and candida(4. 2%)positive,and candida glabrata,penicilium,fusarium and trichosporon asahii positive in one case respectively(2. 1%).④Single-factor analysis showed that morbid state(no remission), neutropenia time>7 days,neutropenia degree<0. 5 × 109 · L-1 ,using broad-spectrum antibiotics and complicating with other organs fungal infection were risk factors of pediatric acute leukemia complicated with fungemia. Multi-factor analysis showed that using broad-spectrum antibiotics was independent risk factors of pediatric acute leukemia with fungemia,OR=28. 3(95%CI:5. 9-136. 2). Conclusion The main pathogen agent of fungimia was candida,especially non-candida albicans. Using broad-spectrum antibiotics was an independent risk factor of pediatric acute leukemia with fungemia.