万古霉素治疗神经外科术后中枢神经系统 感染：一项针对处方剂量的回顾性调查

Treatment of postoperative central nervous system infection with vancomycin：a retrospective survey about the dose

目的：调查万古霉素用于治疗神经外科术后中枢神经系统（CNS）感染的处方剂量。方法采用回顾性研究方法，收集2011年1月至2015年12月首都医科大学附属北京天坛医院神经外科术后应用万古霉素的住院患者信息，筛选出CNS感染患者，提取相关数据并进行数据整理。将日剂量2g或30～60mg/kg定义为用药剂量达标，分析实际用药情况与指南规范之间的差距。结果共有5816例患者应用万古霉素，总计46787日次。其中神经外科术后CNS感染患者1198例（占20.6%），用药总日次14083日次（占30.1%），中位用药日次9日次，中位用药剂量26.0mg/kg；男性占50.8%，中位年龄42.0岁，中位体质量68.0kg。万古霉素最常用的处方剂量是1.0g、12h1次，用药6957日次，占49.4%；日剂量达标率为60.3%。目标性用药患者355例，经验性用药患者843例；目标性用药组患者年龄高于经验性用药组〔岁：44.0（32.5，54.0）比41.0（31.0，52.0），P＜0.05〕，用药日次明显多于经验性用药〔日次：11（6，17）比9（6，12），P＜0.01〕，但是两组日剂量无明显差异〔mg/kg：25.4（20.0，30.3）比26.1（20.9，31.0），g：1.80（1.50，2.00）比1.85（1.50，2.00），均P＞0.05〕，且日剂量均未达标。16.3%（195/1198）的患者存在多疗程用药情况，且各疗程间首疗程用药情况无差异。全组患者临床病死率为1.5%（18/1198），死亡组目标性用药、多疗程用药患者比例较存活组高，用药日次多〔目标性用药：72.2%（13/18）比29.0%（342/1180），＞1个疗程的患者比例：83.3%（15/18）比15.3%（180/1180），总日次：29.0（17.8，45.0）比9.0（6.0，14.0），首疗程日次：11.5（7.5，21.5）比8.0（6.0，12.0），均P＜0.05〕。结论用万古霉素治疗神经外科术后CNS感染的实际临床应用情况欠规范，有必要进一步加强对万古霉素临床应用的宣教，提高对指南的依从性。

Objective To evaluate the dose of vancomycin for the treatment of central nervous system （CNS） infection after neurosurgery. Methods The information of hospitalized patients treated by vancomycin after neurosurgery from January 2011 to December 2015 at Beijing Tiantan Hospital, Capital Medical University was collected retrospectively. The patients with CNS infection were retrieved, the relevant data were extracted and systemized. A daily dose of 2 g or 30-60 mg/kg of vancomycin was thought as the standard, and the difference between the actual dose and the guidelines was analyzed. Results There were 5 816 patients used vancomycin for a total of 46 787 days. The number of patients with CNS infection after neurosurgery was 1 198 （20.6%）, the total treatment course was 14 083 days （30.1%）, the median treatment days was 9, the median daily dose was 26.0 mg/kg; and the percentage of male patient was 50.8%, the median age was 42.0 years, and the median body weight was 68.0 kg. The most commonly used dose and frequency of vancomycin was 1.0 g every 12 hours with 6 957 days （49.4%） and 60.3% daily dose of vancomycin reached the standard. 355 patients were treated to the target and 843 patients were treated empirically, the age of targeted treatment group was older than empirical treatment group [years： 44.0 （32.5, 54.0） vs. 41.0 （31.0, 52.0）, P 〉 0.05]. The mean duration of targeted treatment group was obviously longer than empirical treatment group [days： 11 （6, 17） vs. 9 （6, 12）, P 〉 0.01], but there was no difference in the total daily dose between the two groups [mg/kg： 25.4 （20.0, 30.3） vs. 26.1 （20.9, 31.0）, g： 1.80 （1.50, 2.00） vs. 1.85 （1.50, 2.00）, both P 〈 0.05], and daily dose of both groups did not reached the standard goal. 16.3% patients （195/1 198） received multi-courses therapy and there was no difference among the first course of dose. The clinical mortality of all patients was 1.5% （18/1 198）. The targeted treatment and multi-courses had a higher proportion in the death group, and the treatment durations were longer than the non-death group [the targeted treatment proportion： 72.2% （13/18） vs. 29.0% （342/1 180）, the multi-courses proportion： 83.3% （15/18） vs. 15.3% （180/1 180）, the total treatment duration： 29.0 （17.8, 45.0） vs. 9.0 （6.0, 14.0）, the days of the first course： 11.5 （7.5, 21.5） vs. 8.0 （6.0, 12.0）, all P 〉 0.05]. Conclusions The dose of vancomycin to treat postoperative CNS infection was inappropriate in a majority of patients. Clinician＆#39;s education regarding appropriate vancomycin dosing is recommended to achieve compliance with the guidelines.