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干细胞移植中每日单次剂量庆大霉素的毒性

Toxicity of single daily dose gentamicin in stem cell transplantation.

作者信息

Warkentin D, Ippoliti C, Bruton J, Van Besien K, Champlin R

机构信息

CSU Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver, Canada.

出版信息

Bone Marrow Transplant. 1999 Jul;24(1):57-61. doi: 10.1038/sj.bmt.1701831.

Abstract

To determine the safety of single daily dose (SDD) gentamicin in recipients of stem cell transplantation (SCT), we evaluated all adult patients at MD Anderson Cancer Center who received SDD gentamicin for treatment of febrile neutropenia. Thirty-three patients received gentamicin 5 mg/kg i.v. every 24 h. Mean duration of therapy was 7 days (range 3-32 days). All patients received vancomycin and 17 received cisplatinum. All patients had normal renal function prior to therapy. Serum gentamicin levels were monitored only when renal function deteriorated. The incidence of nephrotoxicity and clinically significant ototoxicity was 3% and 12%, respectively. All four patients who developed ototoxicity had normal renal function before and during therapy. The mean duration of gentamicin therapy was significantly longer in patients who developed ototoxicity, 20 days vs 9 days (P = 0.001). Patients treated with SDD gentamicin for >10 days were more likely to develop ototoxicity (P = 0.045). Single daily dosing of gentamicin was associated with clinically significant ototoxicity in 12% of our patients. A larger randomized EORTC trial evaluating SDD vs MDD amikacin failed to detect a difference in ototoxicity. However, the median duration of therapy was only 8 days. The increased incidence of ototoxicity in our study may be due to prolonged therapy, type of aminoglycoside used, concomitant ototoxic agents, small sample size, or a combination of the above.

摘要

为确定干细胞移植(SCT)受者每日单次剂量(SDD)庆大霉素的安全性,我们评估了MD安德森癌症中心所有接受SDD庆大霉素治疗发热性中性粒细胞减少症的成年患者。33例患者每24小时静脉注射5mg/kg庆大霉素。平均治疗持续时间为7天(范围3 - 32天)。所有患者均接受了万古霉素治疗,17例接受了顺铂治疗。所有患者在治疗前肾功能均正常。仅在肾功能恶化时监测血清庆大霉素水平。肾毒性和具有临床意义的耳毒性发生率分别为3%和12%。所有发生耳毒性的4例患者在治疗前和治疗期间肾功能均正常。发生耳毒性的患者庆大霉素平均治疗持续时间明显更长,分别为20天和9天(P = 0.001)。接受SDD庆大霉素治疗>10天的患者更易发生耳毒性(P = 0.045)。在我们的患者中,12%接受SDD庆大霉素治疗出现了具有临床意义的耳毒性。一项更大规模的评估SDD与每日多次剂量(MDD)阿米卡星的欧洲癌症研究与治疗组织(EORTC)随机试验未能检测到耳毒性方面的差异。然而,治疗的中位持续时间仅为8天。我们研究中耳毒性发生率增加可能是由于治疗时间延长、所用氨基糖苷类药物类型、伴随的耳毒性药物、样本量小或上述因素的综合作用。

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