Division of Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka City, Iwate, 020-8505, Japan.
Division of Hematology, Department of Internal Medicine, Iwate Prefectural Chubu Hospital, Kitakami, Japan.
Ann Hematol. 2019 May;98(5):1209-1216. doi: 10.1007/s00277-019-03634-w. Epub 2019 Mar 1.
Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1-2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124.
中性粒细胞减少伴发热是血液系统恶性肿瘤患者，尤其是急性白血病患者的常见并发症。美罗培南对革兰阳性和革兰阴性菌具有强大而广泛的抗菌活性，被推荐为中性粒细胞减少伴发热患者的一线经验性治疗药物。相比之下，多利培南在中性粒细胞减少伴发热和血液系统恶性肿瘤患者中的安全性和疗效有限。在这项随机、前瞻性、合作、开放性临床试验中，我们比较了多利培南（1.0 g，每 8 小时 1 次）与美罗培南（1.0 g，每 8 小时 1 次）作为中性粒细胞减少伴发热患者的一线经验性抗菌治疗药物。为了评估疗效和安全性，133 例接受化疗期间或化疗后发生中性粒细胞减少伴发热的急性白血病或高危骨髓增生异常综合征住院患者被随机分配至这两种药物组。治疗 3-5 天内无需调整治疗即可退热（即主要终点）的患者比例，多利培南组和美罗培南组之间无显著差异（分别为 60.0%和 45.6%；P=0.136）。然而，治疗 7 天内退热的患者比例在多利培南组显著高于美罗培南组（分别为 78.4%和 60.2%；P=0.037）。两组的不良反应（1-2 级）发生率相似。因此，我们得出结论，多利培南和美罗培南都可安全耐受，用于治疗急性白血病或高危骨髓增生异常综合征伴中性粒细胞减少伴发热的患者，且多利培南的临床疗效不劣于美罗培南。UMIN 临床试验注册编号：000006124。
