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肺炎混合感染小鼠模型中 lascufloxacin 和左氧氟沙星对肺炎链球菌和中间普氏菌的体内药效学。

In vivo pharmacodynamics of lascufloxacin and levofloxacin against Streptococcus pneumoniae and Prevotella intermedia in a pneumonia mixed-infection mouse model.

机构信息

Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, 480-1195, Japan; Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute, 480-1195, Japan.

Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute, 480-1195, Japan.

出版信息

Anaerobe. 2021 Jun;69:102346. doi: 10.1016/j.anaerobe.2021.102346. Epub 2021 Feb 15.

DOI:10.1016/j.anaerobe.2021.102346
PMID:33600958
Abstract

This study aimed to evaluate the antimicrobial activity of a new quinolone, lascufloxacin, for the treatment of complicated pneumonia caused by Streptococcus pneumoniae and Prevotella intermedia using a neutropenic mice pneumonia mixed-infection model. In this study, one S. pneumoniae and four P. intermedia isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the reduction of the bacterial count comparatively to the non-treated mice (log colony forming units (cfu)/mL) obtained in the lungs of the treated mice after 24 h. Consequently, the bacterial densities of S. pneumoniae (KY-9) and P. intermedia (335) in the lungs of control animals were 8.20 ± 0.19 log cfu/mL and 5.26 ± 1.50 log cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log cfu/mL, p < 0.001; levofloxacin 4.30 ± 0.75 log cfu/mL, p < 0.001), but also P. intermedia (lascufloxacin: 1.54 ± 0.57 log cfu/mL, p < 0.001; levofloxacin: 2.79 ± 0.55 log cfu/mL, p = 0.0102). Additionally, levofloxacin demonstrated attenuated antimicrobial efficacies against S. pneumoniae in the mixed-infection model compared with that in the single infection model. In contrast, lascufloxacin showed enhanced antimicrobial activities against S. pneumoniae and P. intermedia in the mixed-infection model. In conclusion, lascufloxacin resulted in enhanced efficacies against S. pneumoniae and P. intermedia, in both the single and mixed-infection models used. These data support the clinical utility of lascufloxacin for use against S. pneumoniae and P. intermedia in the treatment of pneumonia.

摘要

本研究旨在使用中性粒细胞减少症小鼠肺炎混合感染模型,评估新型喹诺酮类药物拉司氟沙星治疗肺炎链球菌和中间普雷沃菌引起的复杂性肺炎的抗菌活性。在本研究中,使用了一株肺炎链球菌和四株中间普雷沃菌分离株。抗菌疗效通过比较治疗后 24 小时小鼠肺部的细菌计数与未经治疗的小鼠(log 菌落形成单位(cfu)/mL)来计算。结果,肺炎链球菌(KY-9)和中间普雷沃菌(335)在对照组动物肺部的细菌密度分别为 8.20±0.19 log cfu/mL 和 5.26±1.50 log cfu/mL。在模拟人类剂量下,拉司氟沙星和左氧氟沙星对肺炎链球菌(拉司氟沙星:1.88±0.43 log cfu/mL,p<0.001;左氧氟沙星:4.30±0.75 log cfu/mL,p<0.001)和中间普雷沃菌(拉司氟沙星:1.54±0.57 log cfu/mL,p<0.001;左氧氟沙星:2.79±0.55 log cfu/mL,p=0.0102)均表现出较高的抗菌活性。此外,与单一感染模型相比,左氧氟沙星在混合感染模型中对肺炎链球菌的抗菌疗效减弱。相比之下,拉司氟沙星在混合感染模型中对肺炎链球菌和中间普雷沃菌的抗菌活性增强。综上所述,拉司氟沙星在单一和混合感染模型中对肺炎链球菌和中间普雷沃菌的疗效增强。这些数据支持拉司氟沙星在治疗肺炎中用于治疗肺炎链球菌和中间普雷沃菌的临床应用。

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