Next-Generation Antimicrobials for One Health: Phages, CRISPR, and Precision Strategies to Combat AMR in LMICs

Background: Antimicrobial resistance (AMR) is a mounting global threat to human, animal, and environmental health. Low- and middle-income countries (LMICs) bear a disproportionate burden due to limited diagnostics, weak regulatory frameworks, and constrained access to novel antibiotics. Conventional therapies are increasingly ineffective, underscoring the urgent need for innovative, precision-targeted interventions. Scope: This narrative review synthesizes emerging next-generation antimicrobial strategies—including bacteriophage therapy, CRISPR-Cas antimicrobials, engineered antimicrobial peptides (AMPs), enzybiotics, and nanotechnology-enabled delivery systems—through a One Health lens. Emphasis is placed on feasibility, scalability, and applicability in LMIC contexts. Key Findings: Preclinical and early clinical studies demonstrate that phages, CRISPR-Cas antimicrobials, and engineered AMPs can reduce multidrug-resistant infections by 60–95%. Enzybiotics and nanotechnology platforms enhance biofilm disruption, stability, and targeted delivery. Combinatorial approaches (e.g., phage–CRISPR, AMP–nanoparticle formulations) further improve antimicrobial efficacy and may mitigate resistance development. Challenges & Outlook: Deployment in LMICs is constrained by delivery optimization, manufacturing costs, regulatory gaps, and infrastructure limitations. Solutions tailored to local production capacity, cold-chain independence, and cost-effectiveness are critical. Integrating these strategies with genomic surveillance, stewardship programs, and One Health governance can accelerate safe and equitable implementation. Tailoring next-generation antimicrobials to LMICs requires cost-effective, locally producible, cold-chain-independent formulations, integrated One Health deployment, and strengthened regulatory and workforce capacity to ensure equitable access and sustainability. Conclusion: Next-generation antimicrobials provide precision-targeted, multi-domain solutions to combat AMR. Strategic combinations, optimized delivery platforms, and LMIC-adapted policies are essential to translating preclinical promise into effective One Health interventions that reduce the global AMR burden.