Focussing on resistance to front-line drugs is the most effective way to combat the antimicrobial resistance crisis

In medical, scientific and political arenas relating to antimicrobial resistance (AMR) there is currently an intense focus on multi-drug resistant pathogens that render last-line antimicrobial treatments ineffective. We question the current emphasis of attention on resistance to last-line antimicrobials, arguing that tackling resistance to front-line antimicrobials has a greater public health benefit. Using AMR monitoring data on 25 drug-pathogen combinations from across Europe, here we show that the presence of front-line pathogen resistance initiates a cascade of resistance selection that ultimately leads to pathogen resistance to last-line antimicrobials. We then interrogate, by modelling the dynamics of resistance evolution, whether 3 key interventions in the strategic response to AMR are more effectively targeted at front-line or last-line treatment. We show that interventions that make front-line therapy more effective by use of antimicrobial adjuvants or front-line resistance diagnostics or by introduction of a novel, front-line antimicrobial all lead to a larger reduction in mortality and morbidity than the same interventions implemented in last-line therapy. Mass use of a newly discovered antimicrobial in front-line infection management to maximise its public health benefit is contrary to current policy but may provide valuable incentives for drug developers. We demonstrate that funding, publications, and attention to those publications do not reflect the importance of front-line antimicrobials and are disproportionately devoted to last-line antimicrobials that account for less than 10% of antimicrobial prescriptions. While studying resistance to last-line drugs is undoubtedly important, our work relays a strong message to public health agencies, funding bodies, and researchers that allocating resources to front-line infections can be a more effective way to combat the antimicrobial resistance crisis.