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

Bacteriophage therapy beyond antibiotics: emerging innovations for infectious and non-infectious diseases

The advancement of synthetic biology and the rise of antimicrobial resistance have led to the development of bacteriophage therapy for more than antibacterial applications. This review focuses on applications to multidrug-resistant infections, biofilm diseases, cancer research, veterinary medicine and animal production. Recent research suggests phages can be used in combination with antibiotics to enhance treatment of large multidrug resistant pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. This could also help to restore antibiotic sensitivity by making bacteria change resistance related structures or mechanisms. Despite this, there are several challenges for the use of phage therapy prior to its widespread clinical application, including phage resistance, difference in patient response, unknown pharmacokinetic parameters, immune issues, and unclear regulatory guidelines. Additionally, in some cases, phages could also play a role in horizontal gene transfer, raising further safety concerns. Beyond antimicrobial therapy, phage display platforms derived from M13, T7 and λ phages have enabled the identification of tumor-targeting peptides, the development of immunomodulatory constructs, and targeted delivery of therapeutic molecules. Over 100 clinical cases and 44 registered trials support the generally favorable safety profile of personalized phage therapy, and highlight the need for better treatment standardization, controlled clinical evaluation, and better regulatory processes. Additionally, engineered phages expressing biofilm degrading enzymes represent promising tools for disrupting matrix-embedded bacterial communities associated with chronic infections and medical devices. In summary, CRISPR-based engineering and genome refactoring highlight the potential of phage-based therapeutics as complements to conventional antimicrobial therapy, although their broader use depends on overcoming biological, clinical, and regulatory challenges.

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

The increasing clinical evidence shows that synthetic biology can effectively overcome the inherent defects of natural bacteriophages, confirming the safety and initial efficacy of bacteriophage therapy.

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.

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 therapy: an alternative approach to combating bacterial resistance

Abstract Antimicrobial resistance is considered one of the greatest threats to global public health, being responsible for millions of deaths annually. Bacteria such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa have developed resistance to multiple classes of antibiotics, making treatment increasingly difficult. In this context, phage therapy has re-emerged as a promising alternative for the treatment of infections caused by multidrug-resistant bacteria. This study was conducted as a literature review based on articles indexed in PubMed, SciELO, and the National Library of Medicine (NLM) databases, considering publications from 2015 to 2025. Studies addressing the efficacy, advantages, limitations, and clinical applications of bacteriophages against multidrug-resistant bacteria were included. Clinical studies demonstrated favorable response rates of up to 66% and complete eradication in 42% of cases treated with personalized phage therapy. In vivo assays showed survival rates ranging from 80% to 100% in murine models infected with multidrug-resistant Acinetobacter baumannii. Recent studies also highlighted the efficacy of phage therapy in urinary tract infections and bacterial biofilm degradation, with reductions exceeding 90% in microbial viability in experimental models. Furthermore, biotechnological advances involving recombinant phages and the CRISPR-Cas system have expanded the therapeutic potential of phage therapy, particularly against biofilms and immune resistance mechanisms. Phage therapy represents an innovative and highly specific strategy for combating infections caused by multidrug-resistant bacteria due to its selective action and self-replication capacity. However, challenges related to immunogenicity, bacterial resistance to phages, and the lack of standardized regulatory frameworks still limit its large-scale clinical application, highlighting the need for further experimental and clinical studies.

Phage therapy: from basic biology to clinical application.