title: Impact of cyadox on human colonic microflora in chemostat models.
abstract: 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.
authors: 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.
authors: Haihong
authors: H
authors: Hao
authors: Weige
authors: W
authors: Guo
authors: Zahid
authors: Z
authors: Iqbal
authors: Guyue
authors: G
authors: Cheng
authors: Xu
authors: X
authors: Wang
authors: Menghong
authors: M
authors: Dai
authors: Lingli
authors: L
authors: Huang
authors: Yulian
authors: Y
authors: Wang
authors: Dapeng
authors: D
authors: Peng
authors: Zhenli
authors: Z
authors: Liu
authors: Zonghui
authors: Z
authors: Yuan
mesh_terms: D000890:Anti-Infective Agents / Q000633:toxicity*; D001441:Bacteroides fragilis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D001644:Bifidobacterium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D003106:Colon / Q000187:drug effects / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D016983:Enterococcus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D005243:Feces / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D019055:No-Observed-Adverse-Effect Level; D011810:Quinoxalines / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D019155:Veterinary Drugs / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D011810:Quinoxalines; D019155:Veterinary Drugs; C020728:cyadox
keywords: Chemostat; Cyadox; Human colonic microflora; Microbiological safety