Association between quinolone use in food animals and gonococcal resistance to ciprofloxacin: an ecological study

Abstract Background Concentrations of fluoroquinolones up to 200-fold lower than the MIC have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration – MSC). We aimed to i) establish what the ciprofloxacin MSC is for Neisseria gonorrhoeae and ii) Assess at a country level if the prevalence of gonococcal ciprofloxacin resistance is associated with the concentration of quinolones used in food animal production (an important determinant of long-term low dose ciprofloxacin exposures in humans). Methods i). To assess if sub-inhibitory ciprofloxacin concentrations could select for de novo generated resistant mutants, susceptible WHO-P was serially passaged at 1, 1/10, 1/100 and 1/1000 of the ciprofloxacin MIC of WHO-P (0.004mg/L) on GC agar plates. ii) Spearman’s correlation was used to assess the association between the prevalence of ciprofloxacin resistance in N. gonorrhoeae and the two independent variables – quinolone use for animals and quinolone consumption by humans. Results Ciprofloxacin concentrations as low as 1/1000 of the MIC of WHO-P were able to select for ciprofloxacin resistance. The prevalence of ciprofloxacin resistance in N. gonorrhoeae was positively associated with quinolone use for food animals (ρ=0.47; P=0.004; N=34). Conclusion Further individual level research is required to assess if low doses of ciprofloxacin from ingested foodstuffs are able to select for ciprofloxacin resistance in N. gonorrhoeae and other species.