Department of Neurology, Klinikum der Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 München, Germany.
Department of Neurology, Klinikum der Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 München, Germany.
Clin Microbiol Infect. 2019 Jan;25(1):108.e9-108.e15. doi: 10.1016/j.cmi.2018.03.039. Epub 2018 Apr 9.
Therapy with antibiotics, dexamethasone, and supportive intensive care has improved the prognosis of pneumococcal meningitis, but mortality remains high. Here, we investigated an adjunctive combination therapy of the non-bacteriolytic antibiotic daptomycin plus several anti-inflammatory agents to identify the currently most promising adjunctive combination therapy for pneumococcal meningitis.
C57BL/6 mice were infected by injection of pneumococci into the cisterna magna. Treatment was begun 21 h after infection, and consisted of ceftriaxone plus (a) dexamethasone, (b) dexamethasone plus daptomycin, (c) daptomycin, (d) daptomycin plus an anti-IL1 antibody, (e) daptomycin plus roscovitine, or (f) daptomycin plus an anti-C5 antibody. Animals were followed until 45 h after infection. Furthermore, adjunctive daptomycin plus anti-C5 antibodies were assessed in a long-term follow-up.
Adjunctive treatment with daptomycin and an anti-C5 antibody was superior to adjunctive dexamethasone and reduced disease symptoms (clinical score 1.1 ± 1.1 versus 5.0 ± 2.7, p < 0.0083), improved explorative activity (open field test 17.8 ± 8.2 versus 7.4 ± 4.3 crossed fields/2 minutes, p < 0.0083), and reduced hearing impairment (thresholds for click stimulus 96.1 ± 14.7 versus 114.8 ± 9.3 dB SPL, p < 0.0083) in the acute stage. Furthermore, explorative activity (14.4 ± 7.3 crossed fields/2 minutes versus 6.3 ± 7.2, p < 0.05) and cognitive function (t-maze test, exploration time previously unknown alley 72.4 ± 14.3 versus 48.7 ± 25.6%, p < 0.05) was improved at 2 weeks after infection. Treatment with daptomycin plus an anti-IL-1β antibody or roscovitine was not of significant benefit in comparison to adjunctive therapy with dexamethasone.
An adjunctive combination of the non-lytic antibiotic daptomycin plus an anti-C5 antibody was superior to standard therapy with adjunctive dexamethasone in the treatment of pneumococcal meningitis.
抗生素、地塞米松和支持性强化治疗改善了肺炎球菌性脑膜炎的预后，但死亡率仍然很高。在这里，我们研究了一种非溶血性抗生素达托霉素联合几种抗炎药物的辅助联合治疗方法，以确定目前治疗肺炎球菌性脑膜炎最有前途的辅助联合治疗方法。
C57BL/6 小鼠通过向枕骨大孔注射肺炎球菌感染。感染后 21 小时开始治疗，包括头孢曲松加（a）地塞米松，（b）地塞米松加达托霉素，（c）达托霉素，（d）达托霉素加抗 IL1 抗体，（e）达托霉素加罗司维汀或（f）达托霉素加抗 C5 抗体。动物一直观察到感染后 45 小时。此外，还评估了辅助性达托霉素联合抗 C5 抗体在长期随访中的作用。
辅助性达托霉素联合抗 C5 抗体治疗优于辅助性地塞米松治疗，可改善疾病症状（临床评分 1.1±1.1 与 5.0±2.7，p<0.0083），改善探索性活动（旷场试验 17.8±8.2 与 7.4±4.3 交叉场/2 分钟，p<0.0083），并减轻听觉损伤（点击刺激阈值 96.1±14.7 与 114.8±9.3 dB SPL，p<0.0083）在急性期。此外，探索性活动（14.4±7.3 交叉场/2 分钟与 6.3±7.2，p<0.05）和认知功能（t 迷宫试验，以前未知通道的探索时间 72.4±14.3 与 48.7±25.6%，p<0.05）在感染后 2 周时得到改善。与辅助性地塞米松治疗相比，达托霉素联合抗 IL-1β 抗体或罗司维汀治疗并无显著益处。
非溶血性抗生素达托霉素联合抗 C5 抗体的辅助联合治疗在治疗肺炎球菌性脑膜炎方面优于标准的辅助地塞米松治疗。
