Safety of prolonged thrice-weekly high-dose daptomycin in a hemodialysis patient with prosthetic valve endocarditis

Michael Bosco, Nadeem Baalbaki
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Abstract

Background

Daptomycin (DAP) is a cyclic lipopeptide antibiotic with in vitro, concentration-dependent bactericidal activity against many clinically relevant gram-positive organisms including Staphylococcus spp. and Enterococcus spp. High-dose DAP (i.e., > 9 mg/kg) has been associated with improved survival outcomes in patients with invasive enterococci infections. Although generally well tolerated, DAP is associated with myopathy and rhabdomyolysis. Limited data regarding the safety of high-dose DAP in hemodialysis (HD) patients, especially with doses ≥ 12 mg/kg, are available. Here, we describe the safety outcomes in a HD patient who received prolonged, thrice-weekly, high-dose DAP. To the best of our knowledge, this is the first case report looking at the safety of long-term DAP doses up to 18 mg/kg.

Case summary

A 65-year-old male with a medical history significant for end-stage renal disease on intermittent HD was diagnosed as having prosthetic valve endocarditis secondary to vancomycin-resistant Enterococcus faecium (VRE). He was deemed a poor surgical candidate and the decision was made for conservative management. DAP was continued for approximately 4 months at a dose of 12 mg/kg on 48-hour interdialytic days and 18 mg/kg on the 72-hour interdialytic day. Creatine phosphokinase (CPK) was monitored once or twice weekly. Average CPK during therapy was 92.3 U/L ± 38.9. Overall, DAP was well tolerated and the patient did not experience any signs or symptoms of myopathy or rhabdomyolysis based on daily review of systems.

Practice implications

Although more data are needed to assess the safety of this particular dosing strategy, our case findings suggest that prolonged DAP doses ≥ 12 mg/kg can be safely considered in those receiving intermittent HD, especially when aggressive treatment is needed for invasive VRE infection.

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在一名患有人工瓣膜心内膜炎的血液透析患者中长期使用每周三次大剂量达托霉素的安全性
背景达托霉素(DAP)是一种环状脂肽类抗生素,对许多临床相关的革兰氏阳性菌(包括葡萄球菌属和肠球菌属)具有体外浓度依赖性杀菌活性。虽然一般耐受性良好,但 DAP 与肌病和横纹肌溶解症有关。目前有关血液透析(HD)患者使用大剂量 DAP(尤其是剂量≥ 12 mg/kg)安全性的数据有限。在此,我们描述了一名长期接受每周三次大剂量 DAP 的血液透析患者的安全性结果。据我们所知,这是第一份研究长期使用剂量高达 18 毫克/千克的 DAP 的安全性的病例报告。病例摘要一位 65 岁的男性患者因终末期肾病而接受间歇性 HD 治疗,被诊断为继发于耐万古霉素肠球菌(VRE)的人工瓣膜心内膜炎。他被认为不适合手术治疗,因此决定采取保守治疗。DAP 持续使用了约 4 个月,剂量为 48 小时间歇日 12 毫克/千克,72 小时间歇日 18 毫克/千克。每周监测一到两次肌酸磷酸激酶(CPK)。治疗期间的平均 CPK 为 92.3 U/L ± 38.9。虽然还需要更多数据来评估这种特殊给药策略的安全性,但我们的病例结果表明,对于接受间歇性 HD 的患者,尤其是需要积极治疗侵袭性 VRE 感染的患者,可以安全地考虑将 DAP 剂量延长至≥ 12 mg/kg。
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