Hao Haihong, Guo Weige, Iqbal Zahid, Cheng Guyue, Wang Xu, Dai Menghong, Huang Lingli, Wang Yulian, Peng Dapeng, Liu Zhenli, Yuan Zonghui
National Reference Laboratory of Veterinary Drug Residues/MOA Key Laboratory of the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
Regul Toxicol Pharmacol. 2013 Dec;67(3):335-43. doi: 10.1016/j.yrtph.2013.08.011. Epub 2013 Aug 22.
The aim of this study was to evaluate the microbiological safety of cyadox, a new member of quinoxaline-1,4-dioxides (QdNOs), on human intestinal flora. Four chemostats containing human fecal flora were exposed to 0, 16, 32, and 128 μg/mL of cyadox, respectively. Bacterial populations, resistance rates of two predominant bacteria and short-chain fatty acids (SCFA) were monitored daily prior to and during drug MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products exposure. Colonization resistance (CR) of each community was determined by three successive daily challenges of Salmonella typhimurium. Efflux pump gene (oqxAB) in the Escherichia coli and Enterococcus strains were analyzed by PCR amplification and DNA sequencing. No change in SCFA was observed after exposure to different concentrations of cyadox. Lower concentration of cyadox (16 μg/mL) had no adverse effect on human microflora. However, higher concentrations of cyadox (32 and 128 μg/mL) could change bacterial population and increase the proportion of resistant E. coli and Enterococcus. More than 26% (12/46) of cyadox resistant E. coli strains contained oqxAB gene, while all the resistant Enterococcus were negative to oqxAB gene. Relationship between the occurrence of oqxAB gene and cyadox exposure is inconclusive. Our data indicated that 16 μg/mL might be the no observed effect concentration (NOEC) of cyadox. Derived microbiological acceptable daily intake (mADI) would be 1552.03 μg/kg d. The data obtained in present study indicated that cyadox was a safe member of QdNOs family of antimicrobial agents.
本研究旨在评估喹喔啉-1,4-二氧化物（QdNOs）新成员喹乙醇对人体肠道菌群的微生物安全性。四个装有人类粪便菌群的恒化器分别暴露于0、16、32和128μg/mL的喹乙醇中。在药物暴露之前及期间，每天监测细菌种群、两种优势菌的耐药率和短链脂肪酸（SCFA）。通过每日连续三次用鼠伤寒沙门氏菌进行挑战来测定每个群落的定植抗力（CR）。通过PCR扩增和DNA测序分析大肠杆菌和肠球菌菌株中的外排泵基因（oqxAB）。暴露于不同浓度的喹乙醇后，未观察到SCFA有变化。较低浓度的喹乙醇（16μg/mL）对人体微生物群没有不良影响。然而，较高浓度的喹乙醇（32和128μg/mL）会改变细菌种群，并增加耐药大肠杆菌和肠球菌的比例。超过26%（12/46）的喹乙醇耐药大肠杆菌菌株含有oqxAB基因，而所有耐药肠球菌的oqxAB基因均为阴性。oqxAB基因的出现与喹乙醇暴露之间的关系尚无定论。我们的数据表明，16μg/mL可能是喹乙醇的未观察到效应浓度（NOEC）。由此得出的微生物可接受每日摄入量（mADI）为1552.03μg/kg·d。本研究获得的数据表明，喹乙醇是QdNOs类抗菌剂中的安全成员。
