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目的:探究癫痫伴有细菌感染患者进行抗菌治疗时,拉莫三嗪(LTG)与利福平(RFP)在其体内相互作用对LTG血药浓度以及癫痫症状的影响。方法:通过神经科门诊收集16例伴有混合菌感染的癫痫患者,回顾性分析在LTG抗癫痫治疗方案中添加RFP进行抗菌治疗的临床资料,采用LC-MS/MS法监测拉莫三嗪血清浓度,通过自身前后对照以及多疗程间对比的方法观察在为期约2个月的RFP治疗前、治疗中以及停止治疗后LTG标准化血药浓度(CDRLTG)、癫痫症状以及发作次数变化。结果:16例患者的CDRLTG在RFP抗菌治疗第3天有明显的下降。相比于RFP治疗前,6例患者的CDRLTG在治疗第6天下降(44.23±15.78)%,9例患者在第14天下降(66.19±15.73)%,两者有显著统计学差异(P=0.020)。1例患者连续服用RFP42 d后,CDRLTG可由2.65μg·mL~(-1)·kg·mg~(-1)下降至0.38μg·mL~(-1)·kg·mg~(-1)。单一疗程中,多例患者在RFP治疗3~5 d时出现癫痫发作,7 d后却未见症状加重或发作频率升高;多疗程相互比较,患者发作症状较前一疗程减轻,次数减少。结论:RFP可重复显著地降低癫痫患者体内LTG浓度,此作用随着合用时间延长而显著加强。长期抗菌治疗有助于改善癫痫患者症状以及降低发作次数。
OBJECTIVE: To investigate the effect of LTG and RFP in vivo on the concentration of LTG and the symptoms of epilepsy in patients with epilepsy and bacterial infection. METHODS: Sixteen patients with epilepsy with mixed bacterial infection were collected through the neurology clinic. The clinical data of anti-bacterial therapy with RFP added to LTG antiepileptic treatment were retrospectively analyzed. The lamotrigine serum was monitored by LC-MS / MS The changes of LTG normalized plasma concentration (CDRLTG), epilepsy symptoms and the number of seizures were observed before and after RFP treatment of about 2 months through self-control and multi-treatment comparison. Results: CDRLTG in 16 patients showed a significant decrease on the 3rd day of RFP antibacterial therapy. The CDRLTG of 6 patients decreased (44.23 ± 15.78)% on the 6th day and that of 9 patients (66.19 ± 15.73)% on the 14th day compared with that before the RFP treatment. There was a significant difference between the two (P = 0.020). In one patient, after continuous administration of RFP for 42 days, CDRLTG decreased from 2.65 μg · mL -1 · kg · mg -1 to 0.38 μg · mL -1 · kg · mg -1. In a single course of treatment, many patients experienced epileptic seizures 3 to 5 days after RFP treatment, but no symptoms or seizure frequency increased after 7 days. Compared with each other, patients’ seizures were relieved and their frequency decreased. Conclusion: RFP can significantly and repeatedly reduce the concentration of LTG in patients with epilepsy, and this effect is significantly enhanced with prolongation of time. Long-term antimicrobial treatment can help to improve the symptoms of epilepsy and reduce the number of attacks.