Institute of Clinical Pharmacology & Toxicology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy.
Ann Pharmacother. 2011 Jul;45(7-8):e37. doi: 10.1345/aph.1P745. Epub 2011 Jul 12.
To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM).
A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53.
High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function.
Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.
通过实时治疗药物监测（TDM），描述 1 例因病态肥胖和肾功能衰竭导致时间依赖性药物暴露优化，成功使用高剂量达托霉素联合连续输注美罗培南治疗的严重蜂窝织炎病例。
一名 63 岁患有病态肥胖症（体重指数 81.6kg/m²）和肾功能衰竭的男性因严重蜂窝织炎被收入急诊病房。患者入院时实验室风险指数坏死性筋膜炎评分为 9 分，给予达托霉素和美罗培南的广谱抗菌治疗。由于肾功能迅速变化，根据密集的 TDM 方案（达托霉素剂量从 1200mg 每 48 小时 30 分钟 1 次调整为 1200mg 每 36 小时 30 分钟 1 次；美罗培南剂量从 0.25g 每 8 小时 6 小时 1 次调整为 500mg 每 4 小时连续输注）进行剂量调整。72 小时内观察到临床反应。然而，血清肌酸激酶（SCK）的突然升高引起了对达托霉素停药的质疑。药物浓度无毒性；因此，我们决定继续治疗。几天后，观察到显著的临床改善和 SCK 正常化。第 29 天，抗生素治疗转换为阿莫西林/克拉维酸加左氧氟沙星，第 53 天出院时停药。
高剂量达托霉素联合连续输注美罗培南可能确保患有疑似早期坏死性筋膜炎的患者有足够的经验性抗菌覆盖。然而，对于病态肥胖和肾功能变化的患者，由于这些药物的亲水性和估计肾功能的标准方法的不准确性，可能会出现重大挑战。
实时 TDM 可能是优化严重蜂窝织炎、病态肥胖和肾功能变化患者使用高剂量达托霉素联合连续输注美罗培南的药物暴露的宝贵方法。
