Kromann Sofie, Kudirkiene Egle, Li Lili, Thoefner Ida, Daldorph Elisabeth, Christensen Jens Peter, Meng Hecheng, Olsen Rikke Heidemann
Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Research Institute of Food Safety and Nutrition, Jinan University, Guangzhou, People's Republic of China.
PLoS One. 2017 Oct 11;12(10):e0185914. doi: 10.1371/journal.pone.0185914. eCollection 2017.
There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens.
由于临床上重要细菌的耐药性增加,当前的抗生素正在失去其价值,因此迫切需要新型抗生素。舍曲林是一种已上市的抗抑郁药物,已被证明在体外可改变细菌活性,包括增加大肠杆菌对抗生素的敏感性。本研究的目的是调查舍曲林的抗菌活性在临床环境下是否能够得到证实,包括舍曲林是否能增强四环素对实验性诱导的家禽上行感染的治疗效果。总共40只鸡被分成四组,每组10只。使用手术感染模型,所有鸡都用4×10³ 个四环素耐药大肠杆菌菌株的菌落形成单位(CFU)进行攻击,随后分别用高剂量舍曲林、四环素、两者的组合进行治疗或不接受治疗。攻击后7天,所有鸡均进行剖检,并对病变进行病理评分。接受高剂量舍曲林或高剂量舍曲林与四环素联合治疗的组中,平均病变评分显著更高(P<0.05)。总之,以高剂量(治疗人类抑郁症最大治疗剂量的四倍)舍曲林作为辅助治疗抗生素耐药大肠杆菌感染会加剧鸡感染的病理结果。