• Phage Therapy in the Antibiotic Resistance Era: A Comprehensive Review of Its Use Against Drug-Resistant Infections
  • Ghazaleh Esfandiari,1,* Mohammad Amin Saghi,2 Saba Soradi Mahkan,3
    1. Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Mashhad, Iran
    2. Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Mashhad, Iran
    3. Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Mashhad, Iran


  • Introduction: Antibiotic resistance in infectious disease is now one of the world's most pressing health concerns, and the post-antibiotic era may establish itself. The excessive use of antibiotics has led to resistant organisms, and infections have emerged as a serious threat worldwide. The rising incidence of such infections, coupled with the dwindling pace of new antibiotic development, has hastened the search for alternative treatments. Bacteriophages, viruses that infect bacteria, are promising candidates against resistant pathogens. Lytic phages can selectively target bacteria, spare eukaryotic cells, and minimize interference with the natural microbiota. Phage therapy has been tested in burns, sepsis, otitis media, and urinary tract infections already with fewer side effects. Endolysins, phage-encoded peptidoglycan-degrading enzymes at the late infection stages, lyse bacteria and have been promoted to treat multidrug-resistant infections. Phages also prevent biofilm formation, further enhancing their therapeutic potential. the aim of this study is to speak about bacteriophages as potential substitutes for antibiotics in treating drug-resistant infections.
  • Methods: A search was conducted in the PubMed database using the key words "bacteriophage," "phage therapy," and "antibiotic resistance." The search was limited to articles published during the years 2020 to 2025. Retrieved articles were reviewed, with particular focus on studies that outlined the application of bacteriophages for the treatment of antibiotic-resistant infections.
  • Results: Studies show that bacteriophages can be highly effective against drug-resistant bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, and MRSA. Promising results have also been reported in infections caused by Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Clinical evidence suggests that phage therapy not only helps reduce bacterial load but also supports recovery in conditions such as bacteremia, urinary tract infections, diabetic foot ulcers, and respiratory infections—especially when used alongside antibiotics. In one clinical trial, more than 85% of patients showed either a significant reduction or complete clearance of infection, without any serious adverse events. Even when phages were used alone, outcomes were encouraging. However, the immune system remains a major obstacle: in many cases, host immune responses can neutralize the phages and limit their therapeutic benefit, particularly in immunocompetent individuals.
  • Conclusion: Bacteriophage therapy represents a promising and innovative approach to counter the global challenge of antibiotic resistance. Evidence from both experimental and clinical studies highlights their potential to effectively target multidrug-resistant pathogens, with encouraging safety profiles. Nonetheless, the successful translation of phage therapy into routine clinical practice requires further optimization, including standardized protocols, large-scale clinical trials, and robust regulatory frameworks. With these advancements, bacteriophages could evolve from experimental tools into reliable therapeutic options for the post-antibiotic age.
  • Keywords: Phage Therapy, Antibiotic, Infection