关键词: 恩诺沙星, 离体恒化器模型, 人体肠道菌群, 残留, 安全评价

Abstract:

【Objective】 The effects of low concentrations of enrofloxacin on human intestinal microflora were evaluated by using chemostat models of the human large bowel, which would be helpful for establishing the microbiological ADI of enrofloxacin. 【Method】 Four steady state microbial communities were established in chemostats using inocula from human feces. Three chemostats were exposed to enrofloxacin (0.2, 2, and 20 mg•L-1, respectively) for 8 days; one served as a no-drug control. Changes of bacterial populations, the relative levels of resistant aerobic and facultative anaerobes to ciprofloxacin, colonization resistance against exogenous Salmonella, and the microflora structure after drug exposure were assayed by plate counting method and PCR-DGGE. 【Result】 Results showed that 2 mg•L-1 and 20 mg•L-1 enrofloxacin significantly reduced flora populations of total aerobic and facultative anaerobes, Escherichia.coli, Enterococcus, and the total anaerobic bacteria (P＜0.05 or P＜0.01). The percentages of resistant aerobic and facultative anaerobes and E.coli were increased significantly after treatment with 0.2, 2 and 20 mg•L-1 enrofloxacin (P＜0.05 or P＜0.01). Seven days after treatment, the percentages of resistant aerobic and facultative anaerobes, and E.coli were decreased, but still higher than the control group (P＜0.01). The number, Shannon’s diversity index and Sorenson’s similarity index of PCR-DGGE lanes decreased significantly after treatment with 20 mg•L-1 enrofloxacin (P＜0.05 or P＜0.01). The colonization barrier against Salmonella was disrupted by 2 mg•L-1 and 20 mg•L-1 enrofloxacin. 【Conclusion】 0.2 mg•L-1 enrofloxacin (equal to 3.67 μg•kg-1 b.w.) can increase the percentage of resistant aerobic flora to ciproflxacin. Thus the ADI (6.2 μg•kg-1 b.w.) of enrofloxacin and ciprofloxacin established by Ministry of Agriculture may affect human intestinal microflora by selecting resistant aerobic flora.

Key words: enrofloxacin, chemostat model, human intestinal microflora, residue, safety evaluation