Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster
Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster
复制标题
小剂量诺氟沙星和环丙沙星治疗会加重仓鼠的钩端螺旋体病。
DOI：
10.1016/j.micpath.2016.11.018
复制
发表时间：
2017-01-01
影响因子：
3.8
通讯作者：
Wu, Rui
中科院分区：
文献类型：
--
作者：
Wu, Dianjun;Zhang, Wenlong;Wu, Rui
抗生素在钩端螺旋体病的治疗中起着重要作用。适当浓度的许多抗生素提高了存活率并减轻了组织损伤，而当给药策略低于亚治疗水平时，观察到更差的治疗效果。在本研究中，我们研究了低剂量诺氟沙星（10，20和30 mg/kg）和环丙沙星（1，2和5 mg/kg）对钩端螺旋体病的仓鼠模型使用问号钩端螺旋体黄疸出血血清型。以诺氟沙星10 mg/kg剂量给药，观察肝、肾、肺等靶器官的组织病理学变化和细菌负荷情况。采用RT-PCR方法检测诺氟沙星组和未治疗组大鼠肺组织中炎性因子IL-1 β和TNF-α的表达。作为阴性对照的所有未处理动物显示50%的存活率，而用10和20 mg/kg剂量的诺氟沙星和1和2 mg/kg剂量的环丙沙星处理的仓鼠显示比未处理组更低的存活率。诺氟沙星10 mg/kg剂量组细菌负荷增加，靶器官组织损伤加重。诺氟沙星组组织中IL-1 β和TNF-α的诱导延迟。我们的研究表明小剂量诺氟沙星和环丙沙星治疗钩端螺旋体病的风险增加。(C)2016爱思唯尔有限公司版权所有
Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1 beta and TNF-alpha was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1 beta and TNF-alpha was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis. (C) 2016 Elsevier Ltd. All rights reserved.