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脑室注射万古霉素治疗开颅术后颅内感染患者的方法学和药代动力学研究。

The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy.

机构信息

Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China.

Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China.

出版信息

J Crit Care. 2015 Feb;30(1):218.e1-5. doi: 10.1016/j.jcrc.2014.09.020. Epub 2014 Oct 2.

DOI:10.1016/j.jcrc.2014.09.020
PMID:25449880
Abstract

OBJECTIVE

The purpose of the study was to investigate the pharmacokinetics of combined intravenous (i.v.) and intracerebroventricular (i.c.v.) vancomycin for patients with intracranial infections after craniotomy and to provide the basis for establishing the intracranial local administration criterion.

METHODS

Fourteen postoperative intracranial infection cases with surgical cavity/ventricular drainages were given vancomycin (1.0 g, i.v. drip for 2 hours, quaque 12 h, and a simultaneous i.c.v. injection of 10 mg). Their blood and cerebral spinal fluid (CSF) specimens were collected at each time point before and after administrations. The concentrations and biochemical properties were measured.

RESULTS

The 1-hour serum vancomycin concentration reached a peak of 46.38 ± 33.39 mg/L; the trough concentration of 48 hours was 8.10 ± 7.11 mg/L; the CSF vancomycin concentration reached a peak of 382.17 ± 421.00 mg/L at 0.25 hours, and the 48-hour trough concentration was 30.82 ± 29.53 mg/L. The inhibitory quotient was calculated at 15.4 by the minimum inhibitory concentration 2 mg/L of target bacteria and had reached the range of 10 to 20 recommended by Infectious Diseases Society of America guidelines. The pH value and osmotic pressure of CSF were found to have no significant changes before and after administration. There was no increasement of seizures and ototoxicity in our study. Before the drug administration and 1 week later, the changes of creatine had no statistically significant, with P > .05.

CONCLUSIONS

The combined i.v. and i.c.v. administration may improve CSF vancomycin concentrations without side effects at the same dosage. Our finding suggests that it can be an option for the treatment of severe intracranial infections after craniotomy; however, its safety and effectiveness need to be confirmed by further large-scale studies.

摘要

目的

研究目的是探讨颅内感染开颅术后患者静脉(i.v.)和脑室内(i.c.v.)万古霉素联合给药的药代动力学,为建立颅内局部给药标准提供依据。

方法

对 14 例术后颅内感染伴手术腔/脑室引流的患者,给予万古霉素(1.0 g,静脉滴注 2 小时,每 12 小时 1 次,同时脑室内注射 10 mg)。在给药前后的各个时间点采集患者的血和脑脊髓液(CSF)标本,测量浓度和生化性质。

结果

1 小时血清万古霉素浓度达到峰值 46.38±33.39mg/L;48 小时谷浓度为 8.10±7.11mg/L;0.25 小时脑脊液万古霉素浓度达到峰值 382.17±421.00mg/L,48 小时谷浓度为 30.82±29.53mg/L。根据目标细菌的最低抑菌浓度 2mg/L 计算抑菌指数为 15.4,达到美国传染病学会指南推荐的 10-20 范围。给药前后 CSF 的 pH 值和渗透压均无明显变化。本研究中未发现癫痫发作和耳毒性增加。给药前和 1 周后,肌酸变化无统计学意义,P>.05。

结论

在相同剂量下,静脉和脑室内联合给药可能会提高 CSF 中万古霉素的浓度,且无副作用。我们的发现表明,对于开颅术后严重颅内感染的治疗,这可能是一种选择;但需要进一步的大规模研究来证实其安全性和有效性。

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