Miura Katsuhiro, Nakagawa Masaru, Takahashi Hiromichi, Uchino Yoshihito, Kodaira Hitomi, Iriyama Noriyoshi, Sakagami Masashi, Ohtake Shimon, Kobayashi Sumiko, Hojo Atsuko, Kurita Daisuke, Kobayashi Yujin, Kusuda Machiko, Hirabayashi Yukio, Hatta Yoshihiro, Takei Masami
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
Int J Hematol. 2016 Mar;103(3):334-40. doi: 10.1007/s12185-015-1926-6. Epub 2015 Dec 29.
We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.
我们开展了一项临床试验，以研究阿贝卡星（ABK）——一种对耐甲氧西林金黄色葡萄球菌（MRSA）具有活性的独特氨基糖苷类药物——在合并高危感染的血液系统恶性肿瘤患者中的疗效和安全性。ABK以约5mg/kg的剂量与各种广谱β-内酰胺类药物静脉联合给药，随后进行治疗药物监测（TDM）。共记录到54次发热或感染发作，44例（81%）进行了TDM。49例（91%）患者的绝对中性粒细胞计数低于500/μl，47例（87%）患者正在接受细胞毒性化疗。在开始使用ABK之前，52例（96%）患者接受过氟喹诺酮类药物（n = 37）和/或广谱β-内酰胺类药物（n = 34）治疗。有10例确诊感染，包括1例MRSA肺炎，44例发热性中性粒细胞减少。所有患者治疗结束时的有效率为80%，达到最大浓度≥16μg/ml或接受TDM指导的ABK剂量调整的患者有效率显著更高（n = 19，95%对71%，P = 0.039）。6例（11%）观察到肾毒性，但总体可接受。本研究表明，在有限条件下，TDM指导的ABK给药可能适用于血液系统恶性肿瘤患者。
