Giampaolo Bucaneve, Stelvio Ballanti, and Albano Del Favero, Ospedale S. Maria della Misericordia, Perugia, Italy; Alessandra Micozzi, Giuseppe Gentile, and Robin Foà, "Sapienza" Università di Roma, Roma; Marco Picardi, A. O. Universitaria "Federico II," Napoli; Nicola Cascavilla, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo; Prassede Salutari, Ospedale Civile "Spirito Santo," Pescara; Giorgina Specchia, Università di Bari, Bari; Rosa Fanci, A. O. Universitaria "Careggi," Firenze; Mario Luppi, A. O. Universitaria Policlinico, Modena; Laura Cudillo, Policlinico Tor Vergata, Roma; Renato Cantaffa, A. O. "Pugliese Ciaccio," Catanzaro; Giuseppe Milone, Policlinico "Vittorio Emanuele," Catania; Monica Bocchia, Policlinico "S. Maria alle Scotte," Siena; Giovanni Martinelli, Istituto Europeo Oncologico, Milano; Massimo Offidani, A. O. Universitaria-Ospedali Riuniti, Ancona; Anna Chierichini, Ospedale S. Giovanni Addolorata, Roma; Francesco Fabbiano, Ospedali Riuniti, Palermo; Giovanni Quarta, Ospedale "A. Perrino," Brindisi; Valeria Primon, Ospedale SS Antonio e Biagio, Alessandria; Bruno Martino, A. O. "Bianchi-Melacrino-Morelli," Reggio Calabria; Annunziata Manna, ASL5, La Spezia; Eliana Zuffa, Ospedale S. Maria delle Croci, Ravenna; and Antonella Ferrari, A. O. Sant'Andrea, Roma.
J Clin Oncol. 2014 May 10;32(14):1463-71. doi: 10.1200/JCO.2013.51.6963. Epub 2014 Apr 14.
Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria.
In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment.
Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups.
The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.
经验性抗生素单药治疗被认为是癌症发热性中性粒细胞减少症患者的标准治疗方法，但由于多药耐药（MDR）细菌引起的感染日益普遍，这种方法可能不够充分。
在这项多中心、开放性、随机、优效性试验中，患有血液系统恶性肿瘤的成年发热、高危中性粒细胞减少症（FhrNP）患者被随机分配接受哌拉西林/他唑巴坦（4.5 g 静脉注射，每 8 小时一次）联合或不联合替加环素（50 mg 静脉注射，每 12 小时一次；负荷剂量 100 mg）。主要终点是发热事件的缓解，而无需修改初始分配的治疗。
共纳入 397 例 FhrNP（联合/单药治疗组，187/203），并纳入意向治疗分析（ITTTA）。ITTTA 显示，接受联合治疗的患者中有 67.9%（127/187）和接受单药治疗的患者中有 44.3%（90/203）的治疗结果成功（绝对风险差异（adr），23.6%；95%CI，14%至 33%；P<.001）。联合方案在菌血症（adr，32.8%；95%CI，19%至 46%；P<.001）和临床确诊感染（adr，36%；95%CI，9%至 64%；P<.01）方面优于单药治疗。两组的死亡率和不良事件数量均有限且相似。
在患有癌症的发热、高危、中性粒细胞减少的血液系统患者中，哌拉西林/他唑巴坦联合替加环素安全、耐受良好，并且比单用哌拉西林/他唑巴坦更有效。在多药耐药微生物引起的感染流行率较高的流行学环境中，这种联合治疗可被视为一线经验性抗生素治疗之一。
