Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy
Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy
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DOI：
10.1056/nejm199907293410502
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发表时间：
1999-07-29
影响因子：
158.5
通讯作者：
Gaya, H
中科院分区：
文献类型：
--
作者：
Kern, WV;Cometta, A;Gaya, H
背景静脉注射抗菌药物已成为经验性治疗癌症患者发热和粒细胞减少症的标准选择。如果口服经验性治疗与静脉治疗一样有效，它将提供诸如改善生活质量和降低成本的优势。方法在一项前瞻性、开放的多中心试验中，我们随机将粒细胞减少症在10天内缓解的发热癌症患者分配到经验组，分别接受口服环丙沙星(750 mg，每日两次)加阿莫西林-克拉维酸(625 mg，每日三次)或标准剂量的头孢曲松加阿米卡星静脉注射治疗。所有患者都住院治疗，直到退烧。这项研究的主要目的是确定两种方案之间是否存在等效性，定义为成功率在10%或更低的绝对差异。结果在第二次中期分析中证明了等效性，试验在353名患者登记后终止。在对312例按方案治疗并可评价的患者的分析中，口服治疗组治疗成功率为86%(95%可信区间，80~91%)，静脉治疗组治疗成功率为84%(95%可信区间，78~90%；P=0.02)。在意向治疗分析中，结果是相似的(分别为80%和77%；P=0.03)，以及发热持续时间、改变方案的时间、改变的原因、治疗持续时间和存活率。两组不良事件的类型略有不同，但发生率相似。结论对于有发热和粒细胞减少的低风险癌症患者，口服环丙沙星联合阿莫西林-克拉维酸片与静脉注射治疗效果相同。(N Engl J Med 1999；341：312-8)(C)1999年，马萨诸塞州医学会。
Background Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost.Methods In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less.Results Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency.Conclusions In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy. (N Engl J Med 1999; 341:312-8.) (C) 1999, Massachusetts Medical Society.