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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic Acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone.
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Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic Acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone.

机译：与单独使用头孢曲松相比，利福平再加头孢曲松治疗实验性脑膜炎可降低脑脊液中脂磷壁酸的浓度并减少神经元损伤。

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摘要

Rifampin (RIF) releases smaller quantities of lipoteichoic acids (LTAs) from Streptococcus pneumoniae than ceftriaxone (CRO). Due to the rapid development of resistance, RIF cannot be used as a single agent for therapy of bacterial meningitis. For this reason, we compared the effect of treatment with RIF followed by treatment with CRO (RIF-CRO) or the effect of treatment with clindamycin (CLI) followed by treatment with CRO (CLI-CRO) to that of CRO alone on the concentrations of LTAs and teichoic acids in vitro. The effects of RIF-CRO on LTA concentrations in cerebrospinal fluid (CSF) and on neuronal injury were investigated in a rabbit model of S. pneumoniae meningitis. In vitro, bacterial titers were effectively reduced by CRO, RIF-CRO, and CLI-CRO when each drug was used at 10 micro g/ml. The levels of release of LTAs after the initiation of therapy were lower in RIF-CRO- and CLI-CRO-treated cultures than in cultures treated with CRO alone (P < 0.05 from 3 to 12 h after initiation of treatment). Similarly, in rabbits, the increase in the amount of LTAs in CSF was lower in RIF-CRO-treated animals than in CRO-treated animals (P = 0.02). The density of dentate apoptotic granular cells was lower after RIF-CRO therapy than after CRO therapy (medians, 58.4 and 145.6/mm(2), respectively; 25th quartiles, 36.3 and 81.7/mm(2), respectively; 75th quartiles, 100.7 and 152.3/mm(2), respectively; P = 0.03). Therefore, initiation of therapy with a protein synthesis-inhibiting antibacterial and continuation of therapy with a combination that includes a beta-lactam may be a strategy to decrease neuronal injury in bacterial meningitis.
机译：与头孢曲松（CRO）相比，利福平（RIF）从肺炎链球菌释放的脂蛋白含量较低（LTA）。由于耐药性的迅速发展，RIF不能用作治疗细菌性脑膜炎的单一药物。因此，我们比较了单独使用CRO与RIF联合CRO（RIF-CRO）或克林霉素（CLI）联合CRO（CLI-CRO）联合治疗的效果。体外LTA和硫磷酸的检测。在兔肺炎链球菌脑膜炎模型中研究了RIF-CRO对脑脊液（CSF）中LTA浓度的影响以及对神经元损伤的影响。在体外，当每种药物以10微克/毫升使用时，CRO，RIF-CRO和CLI-CRO可有效降低细菌滴度。 RIF-CRO和CLI-CRO处理的培养物中LTA释放的水平低于单独CRO处理的培养物中的LTA释放水平（治疗开始后3到12 h，P <0.05）。类似地，在兔子中，RIF-CRO处理的动物的CSF中LTA的增加量低于CRO处理的动物（P = 0.02）。 RIF-CRO治疗后齿状凋亡小细胞的密度低于CRO治疗后（中位数分别为58.4和145.6 / mm（2）;第25四分位数分别为36.3和81.7 / mm（2）;第75四分位数为100.7和152.3 / mm（2），分别为P = 0.03）。因此，用抑制蛋白质合成的抗菌剂开始治疗并用包括β-内酰胺的组合物继续治疗可能是减少细菌性脑膜炎中神经元损伤的一种策略。

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