Innovative biotherapeutics for antimicrobial resistance: From monoclonal antibodies to phage therapy

Antimicrobial resistance (AMR) is a mounting global health crisis projected to cause up to 10 million deaths annually by 2050, threatening human health, food security, and economic stability. Conventional antibiotics are increasingly undermined by diverse resistance mechanisms, declining drug discovery pipelines, and ecological consequences, underscoring the urgent need for innovative therapeutic strategies. This review explores monoclonal antibodies (mAbs) and phage therapy as leading bio-therapeutic alternatives, alongside emerging modalities such as antimicrobial peptides (AMPs), Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated antimicrobials, endolysins, and microbiome-based interventions. A narrative synthesis was conducted using peer-reviewed literature retrieved from PubMed, Scopus, Web of Science, Google Scholar, and EBSCOhost, supplemented by clinical trial registries and global AMR surveillance reports. Inclusion criteria encompassed studies published between 2000 and 2025 addressing biotherapeutics within the One Health framework across human, animal, and environmental domains. Findings highlight that mAbs provide pathogen-specific activity, toxin neutralization, and immune enhancement with reduced risk of cross-resistance. Clinical examples include bezlotoxumab for Clostridioides difficile and raxibacumab for anthrax, demonstrating efficacy in resistant infections. Mechanisms of phage therapy include direct bacteriolysis, biofilm penetration, and adaptability through engineered phages and cocktails, with compassionate clinical use showing promising outcomes in multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii . Other biotherapeutics, including AMPs and endolysins, exhibit broad antimicrobial activity and are progressing through early-stage trials. Despite these advances, challenges persist in regulatory harmonization, manufacturing scalability, and equitable access, particularly in low- and middle-income countries. In conclusion, innovative biotherapeutics represent a critical frontier in AMR control, complementing or supplanting conventional antibiotics. Their integration into clinical practice requires sustained investment, interdisciplinary collaboration, and One Health strategies to ensure global accessibility and longterm efficacy. Addressing scientific gaps, regulatory barriers, and socioeconomic inequities will be essential to realize the transformative potential of these novel therapies in combating AMR.