Phage Therapy Enhanced by Using Engineered Bacteriophages: A Powerful Antibacterial Tool to Address the Dilemma Posed by Multidrug-Resistant Bacterial Infections

Bacteriophage Therapy as a Promising Substitute for Antibiotics: Current Advances, Clinical Applications, and Future Perspectives

Accumulating experimental and clinical evidence indicates that bacteriophage therapy could become an important component of future antimicrobial strategies, and Continued multidisciplinary research, standardized clinical protocols, and well-designed randomized clinical trials are essential to establish its long-term efficacy and safety.

Phage as a prospective arsenal against superbugs

The escalating crisis of antimicrobial resistance (AMR) necessitates the urgent development of alternatives to traditional antibiotics. Bacteriophage (phage) therapy, which utilizes viruses that specifically infect and lyse bacteria, has re-emerged as a promising therapeutic strategy. This review comprehensively examines the current landscape, beginning with the modern, genome-based classification of phages and detailing their key therapeutic advantages, including high specificity, self-amplification, and biofilm-penetrating capability. We explore advanced biotechnological applications such as genetic engineering of phages, the use of phage-derived proteins, and synergistic phage-antibiotic combinations (PAS). The translational workflow from phage sourcing and biobanking to characterization, formulation, and clinical delivery is critically analyzed, alongside major therapeutic areas like chronic wounds and pulmonary infections. Despite promising clinical evidence from compassionate use and trials, significant scientific, regulatory, and commercial hurdles remain. The integration of synthetic biology and artificial intelligence is poised to overcome these challenges, steering phage therapy toward becoming a precise and adaptable component of the modern antimicrobial arsenal.

Phage and CRISPR based precision antimicrobials: a dual strategy against multidrug-resistant bacteria

This review critically examines bacteriophage-based antimicrobials, CRISPR-Cas therapeutic systems, and their emerging integration as CRISPR-armed phages, highlighting their comparative advantages, current limitations, and future potential as promising targeted antimicrobial approach platforms requiring further clinical validation.

The Therapeutic Potential of Phages in Multi-Drug Resistance Infections and Future Directions

Phage therapy has been revisited as a biologically based strategy to tackle the escalating global crisis of multidrug-resistant (MDR) bacterial infections. Distinct from conventional antibiotics, bacteriophages target specific bacterial strains precisely, replicate locally at infection sites, penetrate bacterial biofilms, and exert synergistic effects with multiple antimicrobial agents. These inherent mechanistic advantages minimize collateral damage to the host’s commensal microbiota. However, existing regulatory frameworks—originally established for chemically synthesized, mass-produced drugs—fail to accommodate personalized, living biological phage products, leading to uncertain approval pathways and inconsistent manufacturing supervision. Clinical experience of phage therapy is predominantly derived from compassionate-use cases via multiple administration routes, including intravenous, inhaled, and topical delivery. This review systematically analyzes major challenges restricting clinical application, such as standardized production, quality control, pharmacokinetic characterization, rapid pathogen identification, and regulatory adaptation, as well as the limited performance of fixed phage cocktails against genetically heterogeneous bacterial populations. Current clinical practice demonstrates that phage therapy exhibits acceptable safety profiles across intravenous, inhaled, and topical administration routes, with promising therapeutic outcomes in otherwise untreatable MDR infections. Nevertheless, stable and reproducible clinical outcomes are hindered by multiple scientific and operational obstacles: the absence of unified standards for phage production and quality control, insufficient understanding of route-dependent pharmacokinetics, the imperative demand for rapid pathogen identification to enable precise phage matching, and the limited efficacy of fixed-cocktail regimens against genetically diverse clinical isolates. The successful integration of phage therapy into routine clinical practice relies on coordinated progress in diagnostic infrastructure construction, GMP-compliant phage repository establishment, international regulatory harmonization, and high-quality evidence generation through well-designed clinical trials. Rather than serving as a universal substitute for antibiotics, phage therapy is best implemented as a precision complementary component within comprehensive antimicrobial stewardship strategies.

Bacteriophage purification technologies for advanced clinical translation.

The rising rates of antimicrobial resistance (AMR) have become a significant concern, especially as untreatable infections spiral out of control. This has opened new opportunities for developing novel therapeutic approaches. The therapeutic application of phage therapy, utilizing bacteriophages, has gained importance for combating multidrug-resistant (MDR) pathogens, either as an adjuvant or as an alternative to antibiotics. This review evaluates recent advancements in bacteriophage purification technologies in the context of phage therapy against antibiotic resistance, including their modes of action, prospective pharmacology, host ranges, and co-evolution with bacteria. We have also reviewed conventional and emerging bacteriophage purification techniques that aim to enhance the therapeutic potential of bacteriophages, including microfluidics, aqueous two-phase systems, monolithic columns, and chromatography-based membrane systems for endotoxin removal, to improve contaminant removal while maintaining phage infectivity and structural integrity. These modern and efficient purification strategies are being upgraded as a framework towards highly specific, reliable, scalable, and regulatory-compliant purification platforms. Such advancements aim to facilitate the removal of endotoxins, cell debris, and other impurities while preserving phage infectivity and structural integrity. These components are of great importance for the provision and clinical translation of phage therapy, as there is an urgent need for an efficient purification strategy to ensure high-grade purity, safety, and consistency of phage preparations. We also outline the primary associated challenges of phage resistance, immunogenicity, and manufacturing standardization that hinder the development of phage therapy. While there are hurdles to overcome, the use of phages has the potential to form an integrated approach to personalized medicine in addressing antibiotic-resistant strains in the post-antibiotic era.

Phage therapy: from basic biology to clinical application.