Pulsed antibiotic release into the environment may foster the spread of antimicrobial resistance.

The WHO has identified rising antibiotic resistance as a 'global threat,' highlighting the urgent need to understand how resistance spreads. A key concept is the minimum selective concentration (MSC)-the threshold at which resistant bacteria gain a competitive advantage. While MSC studies typically use single antibiotics under controlled conditions, real-world environments often contain fluctuating levels and mixtures of antibiotics from sources such as wastewater, complicating the dynamics of resistance spread. This study presents a mathematical model that simulates antibiotic accumulation in aquatic systems to evaluate the resulting influence on resistance selection in microbial communities. It incorporates antibiotic inputs, their photolytic and/or biotic degradation, and microbial competition. Results show that antibiotic accumulation from environmental pulses depends on parameters such as pulse frequency and half-life and may drive the selection of resistant strains. Importantly, combinations of antibiotics significantly alter bacterial competition depending on their interaction type. Synergistic combinations can potentially intensify selection for resistance even when individual antibiotic concentrations are below their respective MSCs. These findings help to understand effects of changing concentrations of multiple antibiotics and to plan mitigation strategies.