One of the ways to explain the relatively few effects of doxycycline PEP on AMR (described in the published studies) is that this has been assessed in PrEP populations with very high levels of antimicrobial consumption. If these studies had been done in populations with lower AB consumption, perhaps a clearer link between doxycycline and AMR would have been seen? Is there evidence of a saturation effect of ABs on AMR? In other words if a population has a high consumption of various classes of ABs they are more likely to have higher MICs and reduced elasticity for further MIC increases? Is there epidemiological and experimental support for this? I would expect that in high consumption populations one is more likely to have bacterial strains with induced multidrug exporters that would raise MICs to multiple ABs including tetracyclines. In this setting adding doxycycline may have little effect on further induction of resistance.