Tamura Kazuo
The First Department of Internal Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan.
Int J Antimicrob Agents. 2005 Dec;26 Suppl 2:S123-7; discussion S133-40. doi: 10.1016/j.ijantimicag.2005.08.001. Epub 2005 Oct 24.
The Japan Febrile Neutropenia Study Group (JFNSG) Trial was a multicenter, open, randomized study designed to validate the first Japanese guidelines for the management of neutropenic cancer patients with unexplained fever issued in 1998. The trial compared cefepime monotherapy with cefepime plus amikacin combination therapy in febrile neutropenic patients with hematological disorders. The JFNSG found that monotherapy with cefepime was, in general, as effective as combination therapy. In terms of subset analyses, defervescence appeared to occur more frequently in leukemic patients and in those with profound neutropenia treated with the dual combination. The conclusion of the trial was that the 1998 guidelines were applicable to the Japanese febrile neutropenic patient population. The JFNSG met again in 2003 to revise these guidelines. An important addition to the guidelines was a distinction between low- and high-risk patients. Low-risk febrile neutropenic patients can receive oral ciprofloxacin or levofloxacin, with or without amoxicillin/clavulanic acid, on an outpatient basis, or intravenous (i.v.) monotherapy with cefepime, ceftazidime or a carbapenem. High-risk patients can receive i.v. cefepime, ceftazidime or a carbapenem, or an i.v. dual combination with cefepime, ceftazidime or a carbapenem plus an aminoglycoside. Those patients with a documented infection with methicillin-resistant Staphylococcus aureus should also receive a glycopeptide. It remains to be determined whether existing assessment scoring systems apply to Japanese patients; whether a broad-spectrum cephalosporin plus an aminoglycoside combination is required as the initial management of patients with acute leukemia and/or profound neutropenia; which antibacterial drugs should be used when first- and second-line agents fail; what are the appropriate oral agents and dosing regimens for low-risk patients; whether serology or the polymerase chain reaction should be the preferred marker for initiating preemptive antifungal therapy; and whether the azoles or the candins should be the preferred antifungal agents.
日本发热性中性粒细胞减少症研究组（JFNSG）试验是一项多中心、开放性、随机研究，旨在验证1998年发布的首版日本不明原因发热的中性粒细胞减少癌症患者管理指南。该试验比较了头孢吡肟单药治疗与头孢吡肟加阿米卡星联合治疗在血液系统疾病发热性中性粒细胞减少患者中的效果。JFNSG发现，一般而言，头孢吡肟单药治疗与联合治疗效果相当。在亚组分析方面，白血病患者以及严重中性粒细胞减少患者接受联合治疗时退热似乎更频繁。该试验的结论是，1998年指南适用于日本发热性中性粒细胞减少患者群体。JFNSG于2003年再次开会修订这些指南。指南的一项重要补充是区分低风险和高风险患者。低风险发热性中性粒细胞减少患者可在门诊接受口服环丙沙星或左氧氟沙星治疗，可加用或不加用阿莫西林/克拉维酸，或接受头孢吡肟、头孢他啶或碳青霉烯类药物的静脉单药治疗。高风险患者可接受静脉注射头孢吡肟、头孢他啶或碳青霉烯类药物，或接受头孢吡肟、头孢他啶或碳青霉烯类药物与氨基糖苷类药物的静脉联合治疗。那些有耐甲氧西林金黄色葡萄球菌感染记录的患者还应接受糖肽类药物治疗。现有评估评分系统是否适用于日本患者；急性白血病和/或严重中性粒细胞减少患者的初始治疗是否需要广谱头孢菌素加氨基糖苷类药物联合治疗；一线和二线药物治疗失败时应使用哪些抗菌药物；低风险患者合适的口服药物和给药方案是什么；血清学或聚合酶链反应是否应作为启动抢先抗真菌治疗的首选标志物；以及唑类或棘白菌素类是否应作为首选抗真菌药物，这些问题仍有待确定。
