Antimicrobial resistance (AMR) has emerged as a planetary health emergency, driven not only by the clinical misuse of antibiotics but also by diverse environmental dissemination pathways. This review critically examines the role of environmental compartments—water, soil, and air—as dynamic reservoirs and transmission routes for antibiotic-resistant bacteria (ARB) and resistance genes (ARGs). Recent metagenomic, epidemiological, and mechanistic evidence demonstrates that anthropogenic pressures—including pharmaceutical effluents, agricultural runoff, untreated sewage, and airborne emissions—amplify resistance evolution and interspecies gene transfer via horizontal gene transfer mechanisms, biofilms, and mobile genetic elements. Importantly, it is not only highly polluted rivers such as the Ganges that contribute to the spread of AMR; even low concentrations of antibiotics and their metabolites, formed during or after treatment, can significantly promote the selection and dissemination of resistance. Environmental hotspots such as European agricultural soils and airborne particulate zones near wastewater treatment plants further illustrate the complexity and global scope of pollution-driven AMR. The synergistic roles of co-selective agents, including heavy metals, disinfectants, and microplastics, are highlighted for their impact in exacerbating resistance gene propagation across ecological and geographical boundaries. The efficacy and limitations of current mitigation strategies, including advanced wastewater treatments, thermophilic composting, biosensor-based surveillance, and emerging regulatory frameworks, are evaluated. By integrating a One Health perspective, this review underscores the imperative of including environmental considerations in global AMR containment policies and proposes a multidisciplinary roadmap to mitigate resistance spread across interconnected human, animal, and environmental domains.

The global dissemination of plasmid-mediated mcr genes, which confer resistance to the last-resort antibiotic colistin, represents a critical public health challenge driven by the interplay of clinical, agricultural, and environmental factors. This review examines the genetic and ecological dynamics of mcr-bearing plasmids, focusing on their role in disseminating colistin resistance across diverse bacterial hosts and ecosystems. Key plasmid families demonstrate distinct evolutionary strategies, including IncI2, IncHI2, and IncX4. IncI2 plasmids favor stability in livestock and clinical settings. IncHI2 plasmids, on the other hand, leverage transposons to co-select for multidrug resistance, while IncX4 plasmids achieve global dissemination through streamlined, conjugation-efficient architectures. The pervasive spread of mcr genes is exacerbated by their integration into chromosomes via mobile genetic elements and co-selection with resistance to other antibiotic classes, amplifying multidrug-resistant phenotypes. Environmental reservoirs, food chains, and anthropogenic practices further facilitate cross-niche transmission, underscoring the interconnectedness of resistance under the One Health framework. Addressing this crisis requires coordinated strategies, including reducing colistin misuse in agriculture, enhancing surveillance of high-risk plasmid types, and fostering international collaboration to preserve antimicrobial efficacy and mitigate the threat of untreatable infections.

Background: Phage–antibiotic combinations (PACs) are increasingly proposed for difficult biofilm infections, but planktonic synergy does not reliably predict activity in mature multidrug-resistant (MDR) biofilms. Objective: To identify the biological, pharmacological, evolutionary, methodological, and translational determinants that govern whether phage–antibiotic synergy (PAS) persists in mature MDR biofilms. Methods: This critical narrative review used a structured evidence map updated through 21 August 2026. Fifty-four primary studies met the final operational core criteria after endpoint-eligibility and publication-status verification and were evaluated for biofilm maturity, phage and antibiotic exposure, treatment sequence, resistance evolution, assay choice, and translational level. Main Results: Twenty of 54 studies (37.0%) included at least one qualifying biofilm/PAC condition aged 48 h or longer, and 14 directly compared treatment order. Interaction direction depended on phage identity, bacterial strain, matrix, absolute phage exposure, antibiotic concentration, timing, and endpoint; the schedule maximizing immediate killing did not necessarily best suppress resistance. Nine core studies reached animal models and four human cases met the defined translational criteria, but uncontrolled cases support feasibility rather than comparative efficacy. Negative, antagonistic, and indeterminate outcomes were retained, and CFU, biomass, metabolic, and lysis-based assays could classify the same regimen differently. Conclusions: PAS should be treated as a context-dependent phenotype requiring direct mature-biofilm validation, factorial dose-sequence testing, longitudinal resistance assessment, and site-matched translational confirmation.