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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Comparative In Vivo Efficacies of Tedizolid in Neutropenic versus Immunocompetent Murine Streptococcus pneumoniae Lung Infection Models
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Comparative In Vivo Efficacies of Tedizolid in Neutropenic versus Immunocompetent Murine Streptococcus pneumoniae Lung Infection Models

机译：泰迪唑胺中泰迪唑氏菌与免疫活性鼠链球菌肺炎链球菌肺炎感染模型的比较

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Given that tedizolid exhibits substantial lung penetration, we hypothesize that it could achieve good efficacy against Streptococcus pneumoniae lung infections. We evaluated the pharmacodynamics of tedizolid for treatment of S. pneumoniae lung infections and compared the efficacies of tedizolid human-simulated epithelial lining fluid (ELF) exposures in immunocompetent and neutropenic murine lung infection models. ICR mice were rendered neutropenic via intraperitoneal cyclophosphamide injections and then inoculated intranasally with S. pneumoniae suspensions. Immunocompetent CBA/J mice were inoculated similarly. Single daily tedizolid doses were administered 4 h postinoculation (termed 0 h). Changes in log(10) CFU at 24 h compared with 0-h controls were estimated. Ratios of area under the free-drug concentration-time curve to MIC (fAUC(0-24)/MIC) required to achieve various efficacy endpoints against each isolate were estimated using the Hill equation. Tedizolid doses in neutropenic and immunocompetent mice that mimic the human-simulated ELF exposure were examined. Stasis, 1-log reduction, and 2-log reduction were achieved at fAUC(0-24)/MIC of 8.96, 24.62, and 48.34, respectively, in immunocompetent mice and 19.21, 48.29, and 103.95, respectively, in neutropenic mice. Tedizolid at 40 mg/kg of body weight/day and 55 mg/kg/day in immunocompetent and neutropenic mice, respectively, resulted in ELF AUC(0-24) comparable to that achieved in humans following a 200-mg once-daily clinical dose. These human-simulated ELF exposures were adequate to attain >= 2-log reduction in bacterial burden at 24 h in 3 out of 4 isolates in both models and 1.58-and 0.74-log reductions with the fourth isolate in immunocompetent and neutropenic mice, respectively. Tedizolid showed potent in vivo efficacy against S. pneumoniae in both immunocompetent and neutropenic lung infection models, which support its consideration for S. pneumoniae lung infections.
机译：鉴于泰迪佐德表现出大量的肺渗透，我们假设它可以对肺炎链球菌肺感染进行良好的疗效。我们评估了泰迪唑啉的药效学，用于治疗肺炎肺炎肺部感染，并比较免疫合并和中性细胞鼠肺部感染模型中泰中唑德人模拟上皮衬里液（ELF）曝光的疗效。通过腹膜内环磷酰胺注射注射ICR小鼠，然后用S.肺炎血管悬浮液接种鼻内。免疫合作的CBA / J小鼠类似地接种。单每日柚子剂量施用4小时后常规（称为0小时）。估计与0-H控制相比，24小时对数（10）CFU的变化。利用山地方程估计，估计在麦克风（Fauc（0-24）/ mic）所需的自由药物浓度曲线下的面积比（Fauc（0-24）/ MIC）。检查了中性级和免疫合并小鼠的泰中唑粒剂，用于模拟人模拟的ELF暴露。在8.96,24.62和48.34的Fauc（0-24）/ MIC，分别在免疫竞争小鼠和19.21,48.29和103.95中，在中性小鼠中分别在8.96,24.62和48.34和103.95中实现了STASIS，1-降低降低。分别在40mg / kg的体重/天和55mg / kg /天的免疫活性剂和中性小鼠中的樱桃蛋白，导致ELF AUC（0-24）与在200mg曾经每日临床后的人类达到的人剂量。这些人模拟的ELF曝光是足以获得> = 2-80次在24小时的24小时内减少24小时，分别与免疫活性剂和中性小鼠的第四个分离物中的第四个分离物中的4分离物中的4个分离物中的3个分离物中的34小时。 。泰迪佐德在免疫活性剂和中性肺部感染模型中对S.肺炎的体内疗效表现出有效的。

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