Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Ann Pharmacother. 2012 Dec;46(12):e35. doi: 10.1345/aph.1R412. Epub 2012 Dec 11.
To report the successful treatment of external ventricular-drain (EVD)-associated infection due to vancomycin-resistant Enterococcus faecium (VRE) with intraventricular daptomycin and intravenous linezolid.
A 64-year-old white male with a complicated medical history was admitted to the neurosurgical unit with Scedosporium apiospermum meningitis and hydrocephalus requiring management with a right and left EVD. On day 28, cerebrospinal fluid cultures from the right EVD grew VRE. Despite initiation of intravenous linezolid, cultures from the right EVD remained positive. Intraventricular daptomycin 5 mg daily was initiated and administered into the right EVD for 7 days. Cerebrospinal fluid was collected from EVD outputs and analyzed for daptomycin concentrations. VRE in cultures from the EVD cleared after 1 day of therapy and no adverse effects were noted. Right and left EVD daptomycin concentrations were discordant throughout therapy by at least a 3-fold difference. First-dose peak and trough daptomycin concentrations in the cerebrospinal fluid were 112.2 and 1.34 μg/mL, respectively, for the right EVD and 37.4 and 0.37 μg/mL, respectively, for the left EVD. Daptomycin accumulation was evident after 3 days of therapy.
Varying doses and frequencies of intraventricular daptomycin have been reported effective for VRE ventriculitis. Intraventricular drug distribution may not be homogeneous throughout the central nervous system. Therefore, daptomycin minimum inhibitory concentration for VRE, cerebrospinal fluid communication throughout the central nervous system, EVD output, and the potential for drug accumulation should be considered when selecting a dose and frequency.
Intraventricular daptomycin may be an option for EVD-associated VRE infections that do not respond to conventional therapy. Intraventricular daptomycin 5 mg is a reasonable initial dose in adults with VRE ventriculitis, based on our experience in this patient.
报告一例万古霉素耐药粪肠球菌（VRE）引起的外引流相关脑室感染，采用脑室注射达托霉素联合静脉注射利奈唑胺成功治疗。
一名 64 岁白人男性，有复杂的病史，因耳念珠菌性脑膜炎和脑积水需要行右脑室和左脑室引流术而被收入神经外科病房。第 28 天，右脑室引流的脑脊液培养出 VRE。尽管开始静脉注射利奈唑胺，但右脑室引流的培养结果仍为阳性。开始每天向右侧脑室注入 5mg 达托霉素，持续 7 天。从右脑室引流的脑脊液中收集样本，分析达托霉素浓度。治疗 1 天后，右脑室引流的 VRE 清除，未出现不良反应。在整个治疗过程中，右脑室和左脑室的达托霉素浓度差异至少为 3 倍。右侧脑室第一剂量峰和谷浓度分别为 112.2μg/ml 和 1.34μg/ml，左侧脑室第一剂量峰和谷浓度分别为 37.4μg/ml 和 0.37μg/ml。治疗 3 天后，出现达托霉素蓄积。
已报道不同剂量和频率的脑室注射达托霉素对 VRE 脑室炎有效。脑室药物分布在整个中枢神经系统可能不均匀。因此，在选择剂量和频率时，应考虑 VRE 的达托霉素最小抑菌浓度、整个中枢神经系统的脑脊液连通性、脑室引流的速度和药物蓄积的潜力。
对于常规治疗无效的外引流相关 VRE 感染，脑室注射达托霉素可能是一种选择。根据我们在该患者中的经验，对于 VRE 脑室炎的成人，5mg 的脑室注射达托霉素可能是一个合理的初始剂量。
