Antibiotic treatment influences outcome in murine sepsis: Mediators of increased morbidity

Antibiotic treatment influences outcome in murine sepsis: Mediators of increased morbidity
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DOI:
10.1097/00024382-199808000-00005
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发表时间:
1998-08-01
期刊:
影响因子:
3.1
通讯作者:
Remick, DG
Remick, DG
中科院分区:
医学2区
文献类型:
--
作者:
Newcomb, D;Bolgos, G;Remick, DG

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不同的抗生素治疗可能会影响 Balb/c 小鼠盲肠结扎穿刺 (CLP) 后的生存和生理反应。将广谱亚胺培南 (IMP) 与庆大霉素、克林霉素和环丙沙星的三重抗生素混合物 (3AB) 进行比较。对照小鼠注射 5% 葡萄糖 (D5W)。使用 25 号针进行 CLP 后,植入 Mini-Mitter 来测量温度和活动。治疗从 CLP 后 2 小时注射 1 吨抗生素或 D5W 开始,每 12 小时注射一次,持续 3 天。 IMP 小鼠的存活率高于 3AB 或 D5W 小鼠。从 CLP 后 12 小时注射开始,3AB 总是会引起 D5W 或 IMP 未观察到的深度低温反应。在 CLP 后的第一个晚上,IMP 小鼠的夜间活动水平高于 3AB 或 D5W 小鼠。为了确定这种低温反应的原因并进一步研究抗生素选择可能对小鼠生理学产生的急性影响,在 CLP 后 24 小时注射抗生素后 0.5 和 1.5 小时处死的小鼠的血浆和腹膜中测量了 IL-1、IL-6、TNF 和 KC 以及脂多糖 (LPS) 的动力学表现。与 IMP 或 D5W 小鼠相比,3AB 小鼠的细胞因子和 LPS 浓度在三个时间点的任何一个都没有显着差异。我们的数据表明,与包含 IMP 的治疗相比,包含 3AB 的抗生素治疗会产生更高的发病率和死亡率。然而,这些改变的机制并不是由于细胞因子或脂多糖的全身水平升高。
Different antibiotic treatments may affect the survival and physiological responses of Balb/c mice following cecal ligation and puncture (CLP). The broad spectrum imipenem (IMP) was compared with a triple antibiotic mixture of gentamicin, clindamycin, and ciprofloxacin (3AB). Control mice received injections of 5% dextrose (D5W). After CLP with a 25 gauge needle, Mini-Mitters were implanted to measure temperature and activity. Therapy began with 1 mt injections of antibiotics or D5W 2 h post-CLP and continued every 12 h for 3 days. Survival was higher in IMP mice than in 3AB or D5W mice. Starting with the injection 12 h after CLP, 3AB always induced a profound hypothermic response not observed with D5W or IMP. Nocturnal activity levels were higher in IMP mice compared with 3AB or D5W mice during the first night following CLP. To determine the cause of this hypothermic response and to further investigate the acute effects that antibiotic choice may have on murine physiology, the kinetic appearance of IL-l, IL-6, TNF, and KC as well as lipopolysaccharide (LPS), were measured in the plasma and peritoneum of mice sacrificed at 0.5, and 1.5 h after antibiotic injection at 24 h post-CLP. Cytokine and LPS concentrations in 3AB mice were not significantly different at any of the three time points when compared with IMP or D5W mice. Our data demonstrate that antibiotic therapy consisting of 3AB produces greater morbidity and mortality compared with therapy consisting of IMP. However, the mechanism of these alterations is not due to elevated systemic levels of cytokines or LPS.