Multidisciplinary Approaches to Antimicrobial Resistance: Mechanisms, Combination Therapies, and Model-Informed Optimization

Antimicrobial resistance (AMR) represents one of the most critical threats to global health, undermining the efficacy of standard treatments and complicating the management of infectious diseases. As the discovery pipeline for novel chemical entities slows, relying solely on traditional monotherapies is no longer sufficient. To preserve the utility of existing antibiotics and ensure the success of novel agents, a multidisciplinary strategy is required—one that integrates deep mechanistic understanding with innovative therapeutic combinations and quantitative pharmacological modeling.This Research Topic aims to bridge the gap between fundamental microbiology and translational pharmacology in the field of infectious diseases. We seek to explore how distinct resistance mechanisms—such as efflux pump overexpression, enzymatic degradation, and target modification—can be circumvented through synergistic combination therapies and precision dosing strategies. Furthermore, we will highlight the role of model-informed drug development (MIDD) in optimizing pharmacokinetic/pharmacodynamic (PK/PD) indices across in vitro and in vivo models to predict clinical outcomes and suppress the emergence of resistance.We invite researchers to submit original research and reviews that advance the pharmacological management of infectious diseases. Potential themes include, but are not limited to:•Mechanisms of Action and Resistance: Characterisation of molecular pathways governing drug entry, metabolism, and efflux in multidrug-resistant (MDR) pathogens.•Combination Therapies: Pharmacological evaluation of synergistic drug combinations, including antibiotic-adjuvant pairs and repurposing strategies to overcome specific resistance phenotypes.•Model-Informed Optimization: Application of PK/PD modeling and simulation to optimize dosing regimens and predict bacterial killing versus resistance suppression.•Novel Targets and Screens: Identification of new cellular targets for antimicrobial intervention and the development of mechanistic or phenotypic screens for anti-infective agents.•In Silico Approaches: In silico studies, including virtual screening, molecular docking, and structure‑based modeling, when coupled with experimental validation in vitro and/or in vivo to support mechanistic or pharmacological insights into antimicrobial potency, resistance modulation, or target engagement.•Translational Pharmacology: Studies linking in vitro potency and in vivo efficacy to guide the clinical positioning of novel or repurposed antimicrobial agents, including implications for clinical trial design and treatment guidelines.This Research Topic focuses strictly on pharmacological interventions. Submissions purely focused on clinical epidemiology, retrospective studies without mechanistic insight, or meta-analyses are outside the scope of this collection. Topic editors: Maria Ponticelli, Pornpan Koomanachai Source: https://www.frontiersin.org/research-topics/78019/multidisciplinary-approaches-to-antimicrobial-resistance-mechanisms-combination-therapies-and-model-informed-optimization