Marie J P, Marjanovic Z, Vekhoff A, Bouvet A, Chast F, Levy V, Baudard M, Legrand O, Rio B, Delmer A, Zittoun R
Department of Hematology, Hôtel-Dieu of Paris, France.
Support Care Cancer. 1999 Mar;7(2):89-94. doi: 10.1007/s005200050233.
The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P = 0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P = 0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients.
本试验的目的是评估哌拉西林与他唑巴坦联合用药在控制中性粒细胞减少患者发热方面的潜在优势。在这项单中心研究中，共有247例发热发作的患者被前瞻性随机分组，分别接受我们的标准治疗方案，即头孢他啶3g/天（1g，每日3次）加妥布霉素3mg/kg/天（1.5mg/kg，每日2次），或哌拉西林12g/天加他唑巴坦1.5g/天（4g + 0.5g，每日3次）加妥布霉素3mg/kg/天（1.5mg/kg，每日2次）。头孢他啶组所有持续发热的病例均加用万古霉素，但哌拉西林/他唑巴坦组仅在微生物学证实有耐药时才加用。所有247例发作均通过“意向性治疗”分析进行评估。两组在年龄、性别、基础疾病、接受的化疗、口腔去污、临床和细菌学记录以及中性粒细胞减少的严重程度和持续时间方面匹配良好。含哌拉西林/他唑巴坦的治疗方案（54.4%）比含头孢他啶的治疗方案（37.6%）更频繁地使初始抗菌治疗成功（72小时时无热，无需更换抗生素）（P = 0.008）。在哌拉西林/他唑巴坦治疗期间观察到的严重感染事件（感染性死亡或因感染导致基础疾病治疗延迟）较少（P = 0.02）（2.6%），低于头孢他啶治疗方案（11.3%），尽管根据所采用的规则，使用哌拉西林/他唑巴坦时糖肽类药物的添加频率较低（54.4%对77.4%）。该试验证实了哌拉西林/他唑巴坦联合用药对发热性中性粒细胞减少患者经验性治疗的疗效。这种抗生素联合用药使此类患者经验性糖肽类抗生素的使用显著减少。
