Environmental exposure to antibiotics drives and sustains antibiotic resistance in Neisseria gonorrhoeae: A modelling study

Ciprofloxacin resistance is widespread in Neisseria gonorrhoeae, despite its discontinuation as recommended treatment option in 2007. Unintentional low-level exposure to ciprofloxacin, e.g., environmental or food-borne, might provide sufficiently high selection pressure to maintain resistance and compensate potential fitness costs. We used a mathematical within-host model of gonorrhoea to investigate the effect of low-level ciprofloxacin exposure on susceptibility. We present a mechanistic within-host model of gonococcal infections in the male urethra, to simulate the influence of low-level ciprofloxacin exposures on gonococcal ciprofloxacin susceptibility. We assessed the impact of repeated exposures to varying amounts of ciprofloxacin [Formula] in a chain of sequentially transmitted infections. Daily exposure to at least 0.15mg ciprofloxacin was sufficient to select for low-level resistance. Moreover, in the absence of ciprofloxacin treatment, resistant variants could revert back to variants with lower levels of resistance. However, background exposure can balance fitness costs of resistance and prevent a complete reversion to the fully susceptible variant. Even for human-host restricted pathogens such as Neisseria gonorrhoeae, a One Health approach that considers unintentional antibiotic exposures is needed to avoid the emergence and spread of resistance.