Unlocking the Power of Phage Therapy in Combating Antimicrobial Resistance: Insights from a Systematic Review and Meta-Analysis
Abstract
Background: Epidemiological research about phage therapy is continuing to highlight the potential of phage as an effective treatment option for antimicrobial-resistant (AMR) infections. Bacteriophage are defined as viruses that especially target and lyse the bacterial cells, offering an appropriate and traditional approach in controlling multi drug resistant (MDR) bacterial infections. Purpose: This systematic review and meta-analysis focuses on evaluating the therapeutic efficacy and safety of bacteriophage treatment by measuring bacterial cell reduction in treating MDR infections.
Methodology: An extensive literature search was done using the PubMed / MEDLINE databases, with no time-bound restrictions. The studies focusing on the therapeutic potential of bacteriophage therapy against antimicrobial resistance were included. The quality assessment was done using the Systematic Review Centre for Laboratory Animals Investigations (SYRCLE) scale, and the pooled data were analyzed using I2 statistics to examine the potential of bacteriophage therapy.
Results: A sum of 16 studies were included in this qualitative synthesis and about 7 studies were analyzed quantitatively. This meta-analysis shows that bacteriophage therapy had significant antibacterial capability against MDR pathogens, leading to a substantial decrease in bacterial load and clinical symptoms. The treatment was also associated with a positive safety profile and minimal side effects.
Conclusion: Bacteriophage therapy represents a promising alternative and also as a supplement to antibiotics for the treatment of MDR infections. Although further research is required to make standard protocols and for optimized treatment strategies, phage therapy paves a way for handling the global AMR crisis.
Keywords: Bacteriophage, Viruses, MDR infections, antimicrobial resistance
Keywords:
Viruses, Bacteriophage, MDR infections, antimicrobial resistanceDOI
https://doi.org/10.22270/jddt.v15i9.7370References
1) Lin DM, Koskella B, Lin HC. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther 2017; 8: 162-173.
2) Ling H, Lou X, Luo Q, He Z, Sun M, Sun J. Recent advances in bacteriophage-based therapeutics: Insight into the post-antibiotic era. Acta Pharm Sin B 2022;12: 4348-64.
3) Aranaga C, Pantoja LD, Martínez EA, Falco A. Phage Therapy in the Era of Multidrug Resistance in Bacteria: A Systematic Review. Int J Mol Sci 2022;23: 4577.
4) Zhang M, Zhang T, Yu M, Chen YL, Jin M. The Life Cycle Transitions of Temperate Phages: Regulating Factors and Potential Ecological Implications. Viruses. 2022;14(9):1904. https://doi.org/10.3390/v14091904.
5) Chen Q, Dharmaraj T, Cai PC, et al. Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics. Pharmaceutics. 2022;14(7):1425. https://doi.org/10.3390/pharmaceutics14071425.
6) Alexyuk P, Bogoyavlenskiy A, Alexyuk M, et al. Isolation and Characterization of Lytic Bacteriophages Active against Clinical Strains of E. coli and Development of a Phage Antimicrobial Cocktail. Viruses. 2022;14(11):2381. https://doi.org/10.3390/v14112381.
7) Dhivya K, Aswini S, Hanusha V, Sethumeena S, Supriya A. Evaluating Local Susceptibility Profile of Bacterial Isolates to Various Antibiotics Using Syndromic Antibiogram: A Cross-Sectional Study. Asian Journal of Pharmaceutical Research and Health Care (AJPRHC) 2024;16(1):100-108.
8) Kim MK, Suh GA, Cullen GD, et al. Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches. J Clin Invest. 2025;135(5):e187996. https://doi.org/10.1172/JCI187996.
9) Alqahtani A. Bacteriophage treatment as an alternative therapy for multidrug-resistant bacteria. Saudi Med J.2023;44(12):1222-1231. https://doi.org/10.15537/smj.2023.44.12.20230366.
10) Hitchcock NM, Devequi Gomes Nunes D, Shiach J, et al. Current Clinical Landscape and Global Potential of Bacteriophage Therapy. Viruses. 2023;15(4):1020. https://doi.org/10.3390/v15041020.
11) Gu Liu C, Green SI, Min L, et al. Phage-Antibiotic Synergy Is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry. mBio. 2020;11(4):e01462-20. https://doi.org/10.1128/mBio.01462-20.
12) Subramanian A. Emerging roles of bacteriophage-based therapeutics in combating antibiotic resistance. Front Microbiol. 2024;15:1384164. https://doi.org/10.3389/fmicb.2024.1384164.
13) Fedorov E, Samokhin A, Kozlova Y, et al. Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection. Viruses. 2023;15(2):499. https://doi.org/10.3390/v15020499.
14) Jia HJ, Jia PP, Yin S, et al. Engineering bacteriophages for enhanced host range and efficacy: insights from bacteriophage-bacteria interactions. Front Microbiol. 2023;14:1172635. https://doi.org/10.3389/fmicb.2023.1172635.
15) Chaudhary N, Sharma K, Kaur H, et al. CRISPR-Cas-assisted phage engineering for personalized antibacterial treatments. Indian J Med Microbiol. 2025;53:100771. https://doi.org/10.1016/j.ijmmb.2024.100771.
16) Kakkar A, Kandwal G, Nayak T, et al. Engineered bacteriophages: A panacea against pathogenic and drug resistant bacteria. Heliyon. 2024;10(14):e34333. https://doi.org/10.1016/j.heliyon.2024.e34333.
17) Lavanya D, Dhivya K, Deekshitha P, Pravallika S, Kesini M. Attitude towards Generic Formulations Usage: Narrowing the Gap between Pharmacist and Physicians. International Journal of Pharmacy and Pharmaceutical Sciences (IJPPS) - Vol 11, Issue 1, 2019: 117-20.
18) Furfaro LL, Payne MS, Chang BJ. Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles. Front Cell Infect Microbiol. 2018; 8:376. https://doi.org/10.3389/fcimb.2018.00376.
19) Olawade DB, Fapohunda O, Egbon E, et al. Phage therapy: A targeted approach to overcoming antibiotic resistance. Microb Pathog. 2024;197:107088. https://doi.org/10.1016/j.micpath.2024.107088.
20) Gómez-Ochoa SA, Pitton M, Valente LG, et al. Efficacy of phage therapy in preclinical models of bacterial infection: a systematic review and meta-analysis. Lancet Microbe. 2022;3(12):e956-e968. https://doi.org/10.1016/S2666-5247(22)00288-9.
21) Uyttebroek S, Chen B, Onsea J, et al. Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. Lancet Infect Dis. 2022;22(8):e208-e220. https://doi.org/10.1016/S1473-3099(21)00612-5.
22) Kalelkar PP, Moustafa DA, Riddick M, et al. Bacteriophage-Loaded Poly(lactic-co-glycolic acid) Microparticles Mitigate Staphylococcus aureus Infection and Cocultures of Staphylococcus aureus and Pseudomonas aeruginosa. Adv Healthc Mater. 2022; 11(10):e2102539. https://doi.org/10.1002/adhm.202102539.
23) Onsea J, Post V, Buchholz T, et al. Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study. Microbiol Spectr. 2021;9(3):e0173621. https://doi.org/10.1128/spectrum.01736-21.
24) Chhibber S, Kaur J, Kaur S. Liposome Entrapment of Bacteriophages Improves Wound Healing in a Diabetic Mouse MRSA Infection. Front Microbiol. 2018;9:561. https://doi.org/10.3389/fmicb.2018.00561.
25) Fujiki J, Nakamura T, Nakamura K, et al. Biological properties of Staphylococcus virus ΦSA012 for phage therapy. Sci Rep. 2022; 12(1):21297. https://doi.org/10.1038/s41598-022-25352-6.
26) Brouillette E, Millette G, Chamberland S, et al. Effective Treatment of Staphylococcus aureus Intramammary Infection in a Murine Model Using the Bacteriophage Cocktail StaphLyse™. Viruses. 2023;15(4):887. https://doi.org/10.3390/v15040887.
27) Kifelew LG, Warner MS, Morales S, et al. Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistant Staphylococcus aureus. BMC Microbiol. 2020;20(1):204. https://doi.org/10.1186/s12866-020-01889-w.
28) Teng F, Xiong X, Zhang S, et al. Correction: Teng et al. Efficacy Assessment of Phage Therapy in Treating Staphylococcus aureus-Induced Mastitis in Mice. Viruses. 2024;16(3):319. https://doi.org/10.3390/v16030319.
29) Schweser K, Bozynski CC, Stoker AM, Gull T, Duren D, Cook JL. Bacteriophage Therapy for Acute Fracture-Related Infections: An Effective Treatment When Compared With Antibiotics in a Canine Model. J Orthop Trauma. 2025;39(3):144-152. https://doi.org/10.1097/BOT.0000000000002950
30) Gordillo Altamirano FL, Barr JJ. Phage Therapy in the Postantibiotic Era. Clin Microbiol Rev. 2019;32(2):e00066-18. https://doi.org/10.1128/CMR.00066-18
31) Górski A, Międzybrodzki R, Węgrzyn G, Jończyk-Matysiak E, Borysowski J, Weber-Dąbrowska B. Phage therapy: Current status and perspectives. Med Res Rev. 2020;40(1):459-463. https://doi.org/10.1002/med.21593
32) Nale JY, McEwan NR. Bacteriophage Therapy to Control Bovine Mastitis: A Review. Antibiotics (Basel). 2023;12(8):1307. https://doi.org/10.3390/antibiotics12081307
33) Pires DP, Cleto S, Sillankorva S, Azeredo J, Lu TK. Genetically Engineered Phages: a Review of Advances over the Last Decade. Microbiol Mol Biol Rev. 2016;80(3):523-543. https://doi.org/10.1128/MMBR.00069-15
34) Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, et al. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection. Antimicrob Agents Chemother. 2017;61(10):e00954-17. https://doi.org/10.1128/AAC.00954-17
35) Kortright KE, Chan BK, Koff JL, Turner PE. Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria. Cell Host Microbe. 2019;25(2):219-232. https://doi.org/10.1016/j.chom.2019.01.014
Published
Abstract Display: 700 
PDF Downloads: 505 PDF Downloads: 51 How to Cite
Issue
Section
Copyright (c) 2025 S. Suismitha , V T Jayanii, S Shirly, A Mohammed Aqeel, A Mathesh, K Dhivya
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.