Risk assessment of ciprofloxacin, flavomycin, olaquindox and colistin sulfate based on microbiological impact on human gut biota

Trace levels of veterinary antibiotics that reside in livestock products may disturb the balance of human intestinal microbiota and impair the colonized barrier function, which is critical to protect against the invasion or overgrowth of exogenous pathogens. We investigated the colonization barrier disruption effect of ciprofloxacin, flavomycin, olaquindox and colistin sulfate by the minimum inhibitory concentration (MIC) assay in pure culture of human gut bacteria and evaluated the no-observed-effect-concentration (NOEC) and acceptable daily intake (ADI) based on the microbiological impact. MICs of the antibiotics were tested for total 100 isolates composed of 10 isolates from each of 10 predominant genera of human faeces that were freshly collected from healthy women at 1 × 105 and 1 × 109 colony-forming units (CFU)/ml. MIC assay was also conducted with 10 ATCC standard bacteria species of human fecal microbiota for the comparison with freshly isolated human fecal mirobiota. The most susceptible bacteria were Escherichia coli for ciprofloxacin and colistin sulfate, Fusobacterium spp. for flavomycin and Eubacterium spp. for olaquindox. MIC values were lower at 1 × 105 than at 1 × 109 CFU/ml. The susceptibility of feacal microbiota freshly isolated from healthy women tended to be similar with those of ATCC standard bactera. NOEC (μg/ml) and ADI (μg/kg BW/day) were evaluated as 0.008 and 0.15 for ciprofloxacin, 0.25 and 1 for flavomycin, 0.125 and 3 for olaquindox and 1.0 and 7 for colistin sulfate, respectively.