Peroral Ciprofloxacin Therapy Impairs the Generation of a Protective Immune Response in a Mouse Model for Salmonella enterica Serovar Typhimurium Diarrhea, while Parenteral Ceftriaxone Therapy Does Not
Peroral Ciprofloxacin Therapy Impairs the Generation of a Protective Immune Response in a Mouse Model for Salmonella enterica Serovar Typhimurium Diarrhea, while Parenteral Ceftriaxone Therapy Does Not
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DOI：
10.1128/aac.05819-11
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发表时间：
2012-05-01
影响因子：
4.9
通讯作者：
Hardt, Wolf-Dietrich
中科院分区：
文献类型：
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作者：
Endt, Kathrin;Maier, Lisa;Hardt, Wolf-Dietrich
非伤寒沙门氏菌 (NTS) 会导致自限性腹泻，有时甚至会导致严重疾病。仅在严重病例和免疫功能低下的患者中才考虑抗生素治疗。抗生素治疗的有益效果和适应性免疫反应的后果尚不清楚。我们使用沙门氏菌腹泻小鼠模型来评估环丙沙星（15 mg/kg 体重，胃内注射，每天 2 次，5 天）或肠胃外头孢曲松（50 mg/kg 腹腔注射，5 天）口服治疗的效果，这两种药物是人类患者常用的药物。根据保护性适应性免疫反应的产生、粪便病原体排泄以及无症状排泄者的出现来评估治疗和不良反应。在小鼠模型中，两种疗法均减轻了疾病的严重程度并降低了粪便排出的水平。与临床数据一致，在大多数动物中，治疗结束后 2 至 12 天观察到病原体肠道定植/粪便脱落的反弹。然而，病原体的排出水平和无症状排泄者的出现频率与未经治疗的对照组没有差异。此外，腹腔内用头孢曲松治疗的小鼠产生了适应性免疫，保护小鼠免受野生型肠沙门氏菌血清型鼠伤寒攻击感染的肠病。相反，用环丙沙星胃内治疗的小鼠没有受到保护。因此，抗生素治疗方案可能会破坏适应性免疫反应，但可以优化治疗方案以保持保护性免疫的产生。确定这是否也适用于人类患者可能会很有趣。在这种情况下，小鼠模型可能是进一步机制研究的工具。
Nontyphoidal Salmonella (NTS) species cause self-limiting diarrhea and sometimes severe disease. Antibiotic treatment is considered only in severe cases and immune-compromised patients. The beneficial effects of antibiotic therapy and the consequences for adaptive immune responses are not well understood. We used a mouse model for Salmonella diarrhea to assess the effects of per os treatment with ciprofloxacin (15 mg/kg of body weight intragastrically 2 times/day, 5 days) or parenteral ceftriaxone (50 mg/kg intraperitoneally, 5 days), two common drugs used in human patients. The therapeutic and adverse effects were assessed with respect to generation of a protective adaptive immune response, fecal pathogen excretion, and the emergence of nonsymptomatic excreters. In the mouse model, both therapies reduced disease severity and reduced the level of fecal shedding. In line with clinical data, in most animals, a rebound of pathogen gut colonization/fecal shedding was observed 2 to 12 days after the end of the treatment. Yet, levels of pathogen shedding and frequency of appearance of nonsymptomatic excreters did not differ from those for untreated controls. Moreover, mice treated intraperitoneally with ceftriaxone developed an adaptive immunity protecting the mice from enteropathy in wild-type Salmonella enterica serovar Typhimurium challenge infections. In contrast, the mice treated intragastrically with ciprofloxacin were not protected. Thus, antibiotic treatment regimens can disrupt the adaptive immune response, but treatment regimens may be optimized in order to preserve the generation of protective immunity. It might be of interest to determine whether this also pertains to human patients. In this case, the mouse model might be a tool for further mechanistic studies.