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增加克拉霉素剂量治疗实验性肺炎支原体肺炎的疗效。

Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.

机构信息

Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

J Antimicrob Chemother. 2011 Oct;66(10):2323-9. doi: 10.1093/jac/dkr306. Epub 2011 Jul 25.

Abstract

OBJECTIVES

Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model.

METHODS

BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness.

RESULTS

Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05).

CONCLUSIONS

Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.

摘要

目的

肺炎支原体呼吸道感染是儿童和成人急性呼吸道感染的常见病因。我们评估了增加克拉霉素剂量在肺炎支原体呼吸道感染的小鼠模型中的优化治疗效果。

方法

BALB/c 小鼠经鼻腔单次接种肺炎支原体或 SP4 肉汤(对照)。每天皮下给予克拉霉素(10、25 或 75mg/kg/天)或安慰剂的小鼠进行分组治疗。治疗后 1、2、3、6 和 12 天评估各组小鼠。观察变量包括定量肺炎支原体培养、肺组织病理学评分、支气管肺泡灌洗液(BAL)细胞因子/趋化因子/生长因子浓度和乙酰甲胆碱雾化后评估气道高反应性的肺量计。

结果

克拉霉素的高剂量治疗可显著提高抗菌疗效,减少肺炎支原体定量培养(P<0.05),同时也显著改善疾病严重程度标志物,包括降低肺组织病理学评分、BAL 细胞因子浓度和气道高反应性(P<0.05)。

结论

克拉霉素的剂量递增治疗在治疗实验性肺炎支原体呼吸道感染方面具有显著更高的疗效。

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