Tiede Christoph, Chiriac Ute, Dubinski Daniel, Raimann Florian J, Frey Otto R, Röhr Anka C, Wieduwilt Anna, Eibach Michael, Filmann Natalie, Senft Christian, Zacharowski Kai, Seifert Volker, Mersmann Jan
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe University, 60590 Frankfurt am Main, Germany.
Department of Pharmacy, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Antibiotics (Basel). 2021 Nov 20;10(11):1421. doi: 10.3390/antibiotics10111421.
Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20-30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.
脑膜炎或脑室炎等脑部感染的有效抗生素治疗因脑脊液（CSF）中药物渗透率低而受到阻碍。由于有人提出持续输注美罗培南和万古霉素以及常规治疗药物监测（TDM）可优化脑室炎患者的抗菌药物暴露，因此我们科室实施了个体化给药策略。我们对首批9例接受持续输注和TDM指导的剂量优化治疗（目标浓度为20 - 30mg/L）的脑室炎患者的血清和脑脊液中美罗培南和万古霉素的浓度进行了回顾性分析。初始给药中位数分别为美罗培南8.8g/24h和万古霉素4.25g/24h，结果美罗培南血清中位数浓度为21.3mg/L，万古霉素为24.5mg/L；美罗培南脑脊液浓度为3.4mg/L，万古霉素为1.7mg/L。美罗培南脑脊液渗透率中位数为15%，万古霉素为7%。初始给药时，除1例患者外，所有患者脑脊液浓度均高于1mg/L。根据TDM进行剂量调整可确保所有患者在治疗48小时内脑脊液浓度充足。鉴于渗透率有限，基于肾功能持续输注美罗培南和万古霉素并进行TDM指导的剂量优化似乎是在脑室炎患者中获得足够脑脊液浓度的合理方法。
