Optimizing Antimicrobial Cycling Strategies to Combat Multidrug Resistance

Antimicrobial resistance (AMR) is a major global health challenge that threatens the effectiveness of antimicrobial therapies across human, veterinary, food, and environmental sectors. Although antimicrobial cycling has long been proposed as a stewardship strategy to reduce the emergence of resistant pathogens, its clinical effectiveness remains controversial due to inconsistent evidence and the complexity of bacterial evolution. Recent advances in microbial genomics, rapid diagnostics, evolutionary biology, and computational modelling now offer new opportunities to optimize antimicrobial cycling through precision, evidence-based approaches.Despite decades of investigation, several key questions remain unanswered. Under which conditions is antimicrobial cycling more effective than alternative stewardship strategies? How should cycling protocols be designed to exploit evolutionary trade-offs and collateral sensitivity while minimizing the emergence of multidrug resistance? Can real-time genomic surveillance and rapid diagnostic technologies support adaptive cycling strategies tailored to local epidemiology? Addressing these questions is essential to move antimicrobial cycling from a theoretical concept to an evidence-based clinical and public health intervention.This Research Topic seeks to clarify under which biological, ecological and clinical conditions antimicrobial cycling is effective, how it compares with alternative stewardship strategies such as mixing and combination therapy, and how modern genomic and computational approaches can improve its implementation. This topic aims to provide a multidisciplinary platform to explore innovative approaches for optimizing antimicrobial cycling and delaying the evolution of antimicrobial resistance. We welcome studies evaluating cycling strategies in clinical, veterinary, food-production, and environmental settings, as well as investigations comparing cycling with complementary stewardship approaches such as antibiotic mixing or combination therapy. Contributions exploring the repurposing of older antibiotics, β-lactam/β-lactamase inhibitor combinations, or alternative antimicrobial agents—including bacteriophages, antimicrobial peptides, essential oils, siderophores, and other non-conventional compounds—are encouraged when their application contributes to optimized cycling strategies. We also welcome studies integrating mathematical modelling, evolutionary genetics, collateral sensitivity networks, whole-genome sequencing, CRISPR-based diagnostics, and resistance surveillance to design predictive, adaptive, and data-driven cycling protocols.The sub-topics of interest include:• Optimization of antimicrobial cycling protocols using experimental, clinical, or computational approaches.• Evolutionary mechanisms, collateral sensitivity, and resistance trade-offs underlying cycling strategies.• Comparative studies of antimicrobial cycling, antibiotic mixing, and combination therapy within antimicrobial stewardship programmes only when these are evaluated as alternative or integrated strategies to optimise antimicrobial use and delay resistance evolution.• Repurposing of existing antimicrobials and evaluation of innovative antimicrobial agents within cycling-based stewardship.• Translation of antimicrobial cycling strategies into clinical practice, infection prevention, and public health policies.In this article collection, we welcome the following article types: FAIR² DATA Direct Submission, FAIR² Data, Hypothesis and Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Systematic Review, Technology and Code. Submissions should address antimicrobial cycling or directly contribute to its optimization, implementation, or evaluation. Studies focused solely on the discovery of novel antimicrobial compounds without implications for stewardship or resistance management are outside the scope.By integrating expertise from microbiology, infectious diseases, evolutionary biology, pharmacology, computational sciences, and public health, this Research Topic aims to clarify the role of antimicrobial cycling in modern antimicrobial stewardship. The collection will identify current knowledge gaps, promote interdisciplinary collaboration, and generate evidence to support the development of data-driven strategies that preserve antimicrobial efficacy and reduce the global burden of multidrug-resistant pathogens. Topic editors: Maria Teresa Mascellino, Silpak Biswas, Ning Dong, Chen Xu Source: https://www.frontiersin.org/research-topics/80152/optimizing-antimicrobial-cycling-strategies-to-combat-multidrug-resistance