Adjuvant non-bacteriolytic and anti-inflammatory combination therapy in pneumococcal meningitis: an investigation in a mouse model.
Adjuvant non-bacteriolytic and anti-inflammatory combination therapy in pneumococcal meningitis: an investigation in a mouse model.
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肺炎球菌脑膜炎的辅助非溶菌和抗炎联合治疗：小鼠模型的研究
DOI：
10.1016/j.cmi.2018.03.039
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
U. Koedel
中科院分区：
文献类型：
--
作者：
C. Höhne;B. Angele;T. Hogen;H. W. Pfister;H. Tufekci;U. Koedel
目的抗生素、地塞米松和支持性重症监护治疗改善了肺炎球菌脑膜炎的预后，但死亡率仍然很高。在这里，我们研究了非溶菌抗生素达托霉素与几种抗炎药的辅助联合治疗，以确定目前最有希望的肺炎球菌脑膜炎的辅助联合治疗。治疗在感染后21小时开始，包括头孢曲松+(A)地塞米松，(B)地塞米松+达托霉素，(C)达托霉素，(D)达托霉素+抗IL1抗体，(E)达托霉素+罗可维汀，或(F)达托霉素+抗C5抗体。动物被跟踪，直到感染后45小时。结果达托霉素联合抗C5抗体辅助治疗优于地塞米松辅助治疗，能明显减轻患者的临床症状(临床评分1.1分±1.1分对5.0分±2.7分，P<0.0083)，改善探查活动(旷场试验17.8分±88.2分对7.4分±44.3分/2分钟)。在急性期，听力损害(短声刺激阈值96.1±14.7比114.8±9.3分贝SPL)降低(P<0.0083)。此外，在感染后2周，探索活动度(14.4±77.3越野/2分钟比6.3±77.2，P<0.05)和认知功能(t迷宫测试，探索时间72.4±14.3比48.7±25.6%，P<0.05)得到改善。与地塞米松辅助治疗相比，达托霉素联合抗IL-1β抗体或罗可维汀治疗肺炎球菌脑膜炎疗效不明显。结论非溶血性抗生素达托霉素联合抗C5抗体治疗肺炎球菌性脑膜炎优于常规辅助地塞米松治疗。
ObjectivesTherapy 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.MethodsC57BL/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.ResultsAdjunctive 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.ConclusionsAn 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.
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影响因子：
5.2
作者：
Gerber, P;Stucki, A;Cottagnoud, P
通讯作者：
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细菌性脑膜炎：当前的治疗方法和未来可能的治疗选择
影响因子：
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影响因子：
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DOI：
--
发表时间：
2010
期刊：
The Annals of Pharmacotherapy
影响因子：
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作者：
M Shawn Riser;Christopher M. Bland;C. Rudisill;P. B. Bookstaver
通讯作者：
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影响因子：
14.5
作者：
Schmidt, H;Heimann, B;Nau, R
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Nau, R