Department of Pharmacy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Antimicrob Agents Chemother. 2018 Oct 24;62(11). doi: 10.1128/AAC.01205-18. Print 2018 Nov.
Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute. Within the entire cohort, 42 patients (88%) received L-AMB as empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1 to 313 days). A documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 patients (90%) survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patient developed an increase in serum creatinine levels of grade 3 or higher. In univariate analyses using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.
脂质体两性霉素 B(L-AMB)广泛用于经验性或抢先治疗以及造血干细胞移植(CBT)后侵袭性真菌感染的治疗。我们回顾性分析了 2006 年至 2017 年间我院 48 例成人 CBT 患者应用 L-AMB 的疗效和安全性。在整个队列中,42 例(88%)患者接受 L-AMB 作为经验性或抢先治疗。L-AMB 的日平均剂量和累积剂量中位数分别为 1.20mg/kg/天(范围 0.62-2.60mg/kg/天)和 30.6mg/kg(范围 0.7-241.5mg/kg)。L-AMB 治疗中位时间为 21.5 天(范围 1-313 天)。1 例患者在 L-AMB 治疗期间发生真菌突破感染,43 例(90%)患者在 L-AMB 治疗结束后至少 7 天存活。在 L-AMB 治疗期间,经常观察到 3 级或更高的低钾血症和肝毒性。然而,没有患者发生 3 级或更高的血清肌酐水平升高。使用逻辑回归模型的单变量分析显示,L-AMB 治疗持续时间超过 21 天和 L-AMB 累积剂量超过 30mg/kg 与肾毒性和 3 级低钾血症显著相关。这些数据表明,低剂量 L-AMB 可能对接受 CBT 的成年患者安全且有效。