Daptomycin Dosage Optimization in Renal Impairment Using Model-Informed Precision Dosing.

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Hamza Sayadi, Yeleen Fromage, Marc Labriffe, Clément Danthu, Caroline Monchaud, Jean-Baptiste Woillard
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Abstract

Background: Daptomycin's efficacy and toxicity are closely related to its exposure, which can vary widely among individuals. The patient, a 59-year-old male with an estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73 m² and a weight of 64 kg, was treated with 850 mg of daptomycin every other day for infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). For patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m², the dosing recommendations are not explicitly defined in the endocarditis guidelines. Subsequently, the pharmacology department was contacted to adjust the dosage.

Methods: A population pharmacokinetic model developed by Dvorchik et al. was used for Bayesian estimation of the patient's pharmacokinetic parameters. The 24-hour area under the curve (AUC24) of daptomycin was calculated at steady state using peak and trough plasma samples.

Results: The minimum inhibitory concentration (MIC) of the MRSA strain was 0.25 mg/L. An AUC24/MIC ratio below 666 is associated with higher mortality risk, while an AUC24 above 939 h·mg/L correlates with increased risk of muscular toxicity. Initial AUC24 estimation was 1091 h·mg/L. Following a dosage reduction to 700 mg every other day, the AUC24 increased to 1600 h·mg/L. Further reduction to 500 mg every other day brought the AUC24 down to 750 h mg/L, with two subsequent measurements showing consistent AUC24 values of 500 h·mg/L, which is within the target range.

Conclusions: Daptomycin ended 6 weeks after the initial negative blood culture, with no adverse effects or recurrence of MRSA infection. This case underscores the need for therapeutic drug monitoring and a multidisciplinary approach to adjust daptomycin doses in patients with renal impairment.

在肾功能不全的情况下,利用模型指导的精确给药优化达托霉素剂量
背景:达托霉素的疗效和毒性与暴露量密切相关,而暴露量因人而异。患者是一名59岁的男性,估计肾小球滤过率(eGFR)为12毫升/分钟/1.73平方米,体重64公斤,因耐甲氧西林金黄色葡萄球菌(MRSA)引起的感染性心内膜炎而接受达托霉素治疗,每天服用850毫克达托霉素。对于肾小球滤过率低于 30 mL/min/1.73 m² 的患者,心内膜炎指南中并未明确规定用药建议。随后,我们联系了药学部门以调整剂量:方法:使用 Dvorchik 等人开发的群体药代动力学模型对患者的药代动力学参数进行贝叶斯估计。利用血浆峰值和谷值样本计算达托霉素在稳态时的 24 小时曲线下面积(AUC24):结果:MRSA 菌株的最低抑菌浓度(MIC)为 0.25 mg/L。AUC24/MIC比值低于666与较高的死亡风险有关,而AUC24高于939 h-mg/L则与肌肉毒性风险增加有关。最初的 AUC24 估计值为 1091 h-mg/L。在剂量减少到每隔一天 700 毫克后,AUC24 升至 1600 毫克/升。进一步减量至每隔一天 500 毫克后,AUC24 降至 750 毫克/升,随后两次测量显示 AUC24 值始终为 500 毫克/升,在目标范围内:结论:达托霉素在最初血培养阴性后6周结束治疗,未出现不良反应或MRSA感染复发。本病例强调了对肾功能损害患者进行治疗药物监测和采用多学科方法调整达托霉素剂量的必要性。
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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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