哌拉西林／三唑巴坦治疗血液病发热性中性粒细胞减少症的有效性和安全性的临床研究

Clinical effects and safety of piperacillin/tazobactam in treating neutropenic febrile patients with malignant hematopathy

目的评价哌拉西林／三唑巴坦对治疗血液病发热性中性粒细胞减少症患者的临床疗效和安全性。方法采用前瞻性、非对照、开放性多中心临床试验对中性粒细胞减少伴发热患者进行研究。哌拉西林／三唑巴坦剂量为每8h给予4．5g，缓慢静脉滴注30min以上，在体温恢复正常或中性粒细胞减少症缓解后继续使用至少4～5d。结果共有218例粒缺伴发热血液病患者人选，其中造血干细胞移植组33例，非移植组185例。根据取得临床感染证据的等级不同分为：（1）不明原因发热（FUO）162例（74．31％）；（2）临床确定感染（CDI）33例（15．14％）；（3）微生物学确定感染（MDI）23例（10．55％）。本次临床试验治疗总有效率为65．60％，细菌清除率为71．43％，不良反应发生率为5．04％。治疗起效时间（2．5±1．2）d，平均用药时间（9．4±8．1）d。造血干细胞移植组与非移植组患者疗效比较差异无统计学意义（X2=2．058，P〉0．05），且两者在起效时间上差异亦无统计学意义（t=1．892，P〉0．05）。参加试验粒缺患者经哌拉西林／三唑巴坦治疗后血象白细胞和绝对中性粒细胞计数均较治疗前显著上升（t=4．092，P〈0．01；t=4．248，P〈0．01），治疗前后肝肾功能上无显著性变化。结论本临床研究结果表明哌拉西林／三唑巴坦在治疗血液病粒缺患者合并感染中疗效好、安全，可作为免疫力低下患者合并感染的经验性治疗。

Objective To evaluate the effect and safety of piperacillin/tazobactam on neutropenic febrile patients with Malignant Hematopathy. Methods 218 patients with malignant hematopathy complicated by infectious fever, 162 （74.31%） with fever of unknown origin （FUO）, 33 （ 15.14% ） with clinically defined infection （CDI）, and 23 （10.55%） with microbiologically defined infection （MDI）, underwent intravenous drip of piperacillin/tazobactam at the dose of 4.5 g for 30 min every 8 hours till 4 - 5 d after the temperature returned to normal or neutropenia was relieved. Twenty hours before and after treatment blood routine, blood biochemical and electrolytes, and bacteriological examination, chest X-ray examination were conducted. The changes of symptoms and signs were observed. Results The total effective rate was 65.60% , the bacteria clearance rate was 71.43%, and the adverse reaction rate was 5.04%. The average defervescence time was （2.5 ± 1.2） days, and the duration of antibiotic therapy was （9. 4 ± 8. 1 ） days. There were not significant differences in the curative effect and defervescence time between the patients undergoing chemotherapy and those undergoing hematopoietic stem cell transplantation （ X2 = 2. 058, P 〉 0.05, and t = 1. 892, P 〉 0.05 ）. After the piperacillin/tazobactam treatment the white blood cell count and absolute neutrophile granulocyte count of the patients significantly increased （t = 4. 092, P 〈0.01;t = 4. 248,P 〈 0.01 ）. However, the hepatic and renal functions did not change obviously after treatment. Conclusions Piperacillin/tazobactam therapy is effective and safe empirical antibacterial therapy in febrile neutropenie patients with hematological malignancies.