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Abstract:
Antimicrobial resistance is one of the major public health threats of the 21st century. There
is a pressing need to adopt more efficient treatment strategies in order to prevent the
emergence and spread of resistant strains. The common approach is to treat patients
with high drug doses, both to clear the infection quickly and to reduce the risk of de novo
resistance. Recently, several studies have argued that, at least in some cases, low-dose
treatments could be more suitable to reduce the within-host emergence of antimicrobial
resistance. However, the choice of a drug dose may have consequences at the population
level, which has received little attention so far. Here, we study the influence of the drug
dose on resistance and disease management at the host and population levels. We
develop a nested two-strain model and unravel trade-offs in treatment benefits between
an individual and the community. We use several measures to evaluate the benefits of any
dose choice. Two measures focus on the emergence of resistance, at the host level and at
the population level. The other two focus on the overall treatment success: the outbreak
probability and the disease burden. We find that different measures can suggest different
dosing strategies. In particular, we identify situations where low doses minimize the risk
of emergence of resistance at the individual level, while high or intermediate doses prove
most beneficial to improve the treatment efficiency or even to reduce the risk of resistance
in the population.
