Resist or perish: fate of a microbial population subjected to a periodic presence of antimicrobial

TL;DR

This study models how periodic antimicrobial exposure influences microbial resistance evolution and population extinction, revealing that treatment efficacy depends on antimicrobial mode and exposure timing.

Contribution

It introduces a stochastic model analyzing resistance evolution under periodic antimicrobial exposure, highlighting the impact of drug mode and exposure frequency on eradication success.

Findings

Fast alternations favor resistance establishment unless antimicrobial increases death rate.

Longer periods lead to population extinction upon first antimicrobial addition.

Biocidal drugs are more effective than biostatic drugs in treatment regimes.

Abstract

The evolution of antimicrobial resistance can be strongly affected by variations of antimicrobial concentration. Here, we study the impact of periodic alternations of absence and presence of antimicrobial on resistance evolution in a microbial population, using a stochastic model that includes variations of both population composition and size, and fully incorporates stochastic population extinctions. We show that fast alternations of presence and absence of antimicrobial are inefficient to eradicate the microbial population and strongly favor the establishment of resistance, unless the antimicrobial increases enough the death rate. We further demonstrate that if the period of alternations is longer than a threshold value, the microbial population goes extinct upon the first addition of antimicrobial, if it is not rescued by resistance. We express the probability that the population is eradicated upon the first addition of antimicrobial, assuming rare mutations. Rescue by resistance can happen either if resistant mutants preexist, or if they appear after antimicrobial is added to the environment. Importantly, the latter case is fully prevented by perfect biostatic antimicrobials that completely stop division of sensitive microorganisms. By contrast, we show that the parameter regime where treatment is efficient is larger for biocidal drugs than for biostatic drugs. This sheds light on the respective merits of different antimicrobial modes of action.