Impact of cyadox on human colonic microflora in chemostat models.

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.