Exploiting ecology in drug pulse sequences in favour of population reduction

TL;DR

This study models two-species population dynamics under drug treatment, showing that short, periodic pulses exploiting ecological competition can be more effective for population extinction than prolonged treatments.

Contribution

It introduces a deterministic model analyzing how ecological competition influences optimal drug pulse scheduling for population eradication.

Findings

Shorter, periodic drug pulses can outperform longer treatments due to species competition.

There exist timescales where low-stress regimes are as effective as high-stress regimes.

Ecological competition can be exploited to optimize treatment timing for better outcomes.

Abstract

A deterministic population dynamics model involving birth and death for a two-species system, comprising a wild-type and more resistant species competing via logistic growth, is subjected to two distinct stress environments designed to mimic those that would typically be induced by temporal variation in the concentration of a drug (antibiotic or chemotherapeutic) as it permeates through the population and is progressively degraded. Different treatment regimes, involving single or periodical doses, are evaluated in terms of the minimal population size (a measure of the extinction probability), and the population composition (a measure of the selection pressure for resistance or tolerance during the treatment). We show that there exist timescales over which the low-stress regime is as effective as the high-stress regime, due to the competition between the two species. For multiple periodic treatments, competition can ensure that the minimal population size is attained during the first pulse when the high-stress regime is short, which implies that a single short pulse can be more effective than a more protracted regime. Our results suggest that when the duration of the high-stress environment is restricted, a treatment with one or multiple shorter pulses can produce better outcomes than a single long treatment. If ecological competition is to be exploited for treatments, it is crucial to determine these timescales, and estimate for the minimal population threshold that suffices for extinction. These parameters can be quantified by experiment.