Exploration of Drug Science

Table 1. Comparative mechanistic and clinical properties of antibiotics vs. bacteriophages.

Dimension	Antibiotics	Bacteriophage therapy	Clinical implication
Nature of agent	Small-molecule chemical	Replicating biological entity	Different regulatory and PK frameworks required
Target flexibility	Fixed molecular targets	Adaptable receptor targeting	Resistance dynamics fundamentally differ
Activity requirement	Active bacterial metabolism	Can act on dormant/biofilm cells	Advantage in chronic infections
Dose-response predictability	High	Variable, context-dependent	Limits standardization
In vivo amplification	None	Yes (host-dependent)	Complicates PK/PD modeling
Resistance trajectory	Accumulative	Oscillatory (coevolution)	Resistance may carry fitness costs
Empiric usability	High	Low	Limits acute-care use
Clinical scalability	Mature	Experimental	Adoption depends on infrastructure

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PK: pharmacokinetic; PD: pharmacodynamic.

Declarations

Author contributions

RHAR: Conceptualization, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. DEN: Visualization, Writing—original draft, Writing—review & editing. AWI: Supervision, Validation, Visualization, Writing—review & editing. SIA: Writing—original draft, Writing—review & editing. KMSA: Writing—original draft, Writing—review & editing. ASF: Writing—original draft, Writing—review & editing. MSA: Writing—original draft. MAZ: Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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References

Yue Y, Xu Z, Soteyome T, Premarathna M, Yin X, Liu J. Phage Encapsulation and Delivery Technology: A Strategy for Treating Drug-Resistant Pathogenic Microorganisms. Pharmaceuticals (Basel). 2025;18:1688. [DOI] [PubMed] [PMC]

Aljeldah MM. Antimicrobial Resistance and Its Spread Is a Global Threat. Antibiotics (Basel). 2022;11:1082. [DOI] [PubMed] [PMC]

Niazi SK. Bacteriophage Therapy: Discovery, Development, and FDA Approval Pathways. Pharmaceuticals (Basel). 2025;18:1115. [DOI] [PubMed] [PMC]

Mboowa G. Reviewing the journey to the clinical application of bacteriophages to treat multi-drug-resistant bacteria. BMC Infect Dis. 2023;23:654. [DOI] [PubMed] [PMC]

Subramanian A. Emerging roles of bacteriophage-based therapeutics in combating antibiotic resistance. Front Microbiol. 2024;15:1384164. [DOI] [PubMed] [PMC]

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;8:162–73. [DOI] [PubMed] [PMC]

Osman A, Kotey FCN, Odoom A, Darkwah S, Yeboah RK, Dayie NTKD, et al. The Potential of Bacteriophage-Antibiotic Combination Therapy in Treating Infections with Multidrug-Resistant Bacteria. Antibiotics (Basel). 2023;12:1329. [DOI] [PubMed] [PMC]

Wang Y, Yu Y. Phage therapy as a revitalized weapon for treating clinical diseases. Microbiome Res Rep. 2025;4:35. [DOI] [PubMed] [PMC]

Zalewska-Piątek B, Piątek R. Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development. Pharmaceuticals (Basel). 2021;14:331. [DOI] [PubMed] [PMC]

10.

Au TY, Assavarittirong C. Combating antimicrobial resistance: an evidence-based overview of bacteriophage therapy. Postgrad Med J. 2023;99:654–60. [DOI] [PubMed]

11.

Kortright KE, Chan BK, Koff JL, Turner PE. Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria. Cell Host Microbe. 2019;25:219–32. [DOI] [PubMed]

12.

Nikolich MP, Filippov AA. Bacteriophage Therapy: Developments and Directions. Antibiotics (Basel). 2020;9:135. [DOI] [PubMed] [PMC]

13.

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. [DOI] [PubMed] [PMC]

14.

Olawade DB, Fapohunda O, Egbon E, Ebiesuwa OA, Usman SO, Faronbi AO, et al. Phage therapy: A targeted approach to overcoming antibiotic resistance. Microb Pathog. 2024;197:107088. [DOI] [PubMed]

15.

Furfaro LL, Payne MS, Chang BJ. Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles. Front Cell Infect Microbiol. 2018;8:376. [DOI] [PubMed] [PMC]

16.

Skliros D, Kalatzis PG, Kalloniati C, Komaitis F, Papathanasiou S, Kouri ED, et al. The Development of Bacteriophage Resistance in Vibrio alginolyticus Depends on a Complex Metabolic Adaptation Strategy. Viruses. 2021;13:656. [DOI] [PubMed] [PMC]

17.

Hatfull GF, Dedrick RM, Schooley RT. Phage Therapy for Antibiotic-Resistant Bacterial Infections. Annu Rev Med. 2022;73:197–211. [DOI] [PubMed]

18.

Golkar Z, Bagasra O, Pace DG. Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. J Infect Dev Ctries. 2014;8:129–36. [DOI] [PubMed]

19.

Zhang M, Zhang T, Yu M, Chen Y, Jin M. The Life Cycle Transitions of Temperate Phages: Regulating Factors and Potential Ecological Implications. Viruses. 2022;14:1904. [DOI] [PubMed] [PMC]

20.

Fischetti VA. Bacteriophage endolysins: a novel anti-infective to control Gram-positive pathogens. Int J Med Microbiol. 2010;300:357–62. [DOI] [PubMed] [PMC]

21.

Kunisch F, Campobasso C, Wagemans J, Yildirim S, Chan BK, Schaudinn C, et al. Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs. Nat Commun. 2024;15:8572. [DOI] [PubMed] [PMC]

22.

Jdeed G, Kravchuk B, Tikunova NV. Factors Affecting Phage-Bacteria Coevolution Dynamics. Viruses. 2025;17:235. [DOI] [PubMed] [PMC]

23.

Hsu BB, Gibson TE, Yeliseyev V, Liu Q, Lyon L, Bry L, et al. Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model. Cell Host Microbe. 2019;25:803–14. [DOI] [PubMed] [PMC]

24.

Loc-Carrillo C, Abedon ST. Pros and cons of phage therapy. Bacteriophage. 2011;1:111–4. [DOI] [PubMed] [PMC]

25.

Orozco-Ochoa AK, González-Gómez JP, Quiñones B, Campo NC, Valdez-Torres JB, Chaidez-Quiroz C. Bacteriophage Indie resensitizes multidrug-resistant Acinetobacter baumannii to antibiotics in vitro. Sci Rep. 2025;15:11578. [DOI] [PubMed] [PMC]

26.

Zhang S, Ahn J. Phage Therapy as a Novel Alternative to Antibiotics Through Adaptive Evolution and Fitness Trade-Offs. Antibiotics (Basel). 2025;14:1040. [DOI] [PubMed] [PMC]

27.

Romero-Calle D, Benevides RG, Góes-Neto A, Billington C. Bacteriophages as Alternatives to Antibiotics in Clinical Care. Antibiotics (Basel). 2019;8:138. [DOI] [PubMed] [PMC]

28.

Cui L, Watanabe S, Miyanaga K, Kiga K, Sasahara T, Aiba Y, et al. A Comprehensive Review on Phage Therapy and Phage-Based Drug Development. Antibiotics (Basel). 2024;13:870. [DOI] [PubMed] [PMC]

29.

Belay WY, Getachew M, Tegegne BA, Teffera ZH, Dagne A, Zeleke TK, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;15:1444781. [DOI] [PubMed] [PMC]

30.

Mobarezi Z, Esfandiari AH, Abolbashari S, Meshkat Z. Efficacy of phage therapy in controlling staphylococcal biofilms: a systematic review. Eur J Med Res. 2025;30:605. [DOI] [PubMed] [PMC]

31.

Gómez-Ochoa SA, Pitton M, Valente LG, Vesga CDS, Largo J, Quiroga-Centeno AC, et al. Efficacy of phage therapy in preclinical models of bacterial infection: a systematic review and meta-analysis. Lancet Microbe. 2022;3:e956–68. [DOI] [PubMed]

32.

Danis-Wlodarczyk K, Vandenheuvel D, Jang HB, Briers Y, Olszak T, Arabski M, et al. A proposed integrated approach for the preclinical evaluation of phage therapy in Pseudomonas infections. Sci Rep. 2016;6:28115. [DOI] [PubMed] [PMC]

33.

Chavan, R, Purandare K. Bacteriophage therapy inspired new age technologies to control antimicrobial resistance. J Umm Al-Qura Univ Appll Sci. 2025. [DOI]

34.

Qi M, Tay A. Phage-nanomaterial platforms for precision antimicrobial therapy: from design to therapeutic application. Nanoscale. 2025;17:21423–57. [DOI] [PubMed]

35.

Palma M, Qi B. Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections. Infect Dis Rep. 2024;16:1127–81. [DOI] [PubMed] [PMC]

36.

Fawcett NJ, Jones N, Quan TP, Mistry V, Crook D, Peto T, et al. Antibiotic use and clinical outcomes in the acute setting under management by an infectious diseases acute physician versus other clinical teams: a cohort study. BMJ Open. 2016;6:e010969. [DOI] [PubMed] [PMC]

37.

Mo Y, Tan WC, Cooper BS. Antibiotic duration for common bacterial infections-a systematic review. JAC Antimicrob Resist. 2025;7:dlae215. [DOI] [PubMed] [PMC]

38.

Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. Mayo Clin Proc. 2011;86:156–67. [DOI] [PubMed] [PMC]

39.

Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing. Clin Ther. 2016;38:1930–47. [DOI] [PubMed] [PMC]

40.

Diop M, Bassoum O, Ndong A, Wone F, Tamouh AG, Ndoye M, et al. Prevalence of multidrug-resistant bacteria in healthcare and community settings in West Africa: systematic review and meta-analysis. BMC Infect Dis. 2025;25:292. [DOI] [PubMed] [PMC]

41.

Patangia DV, Ryan CA, Dempsey E, Ross RP, Stanton C. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022;11:e1260. [DOI] [PubMed] [PMC]

42.

Francino MP. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol. 2016;6:1543. [DOI] [PubMed] [PMC]

43.

Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, et al.; Antibacterial Resistance Leadership Group. Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob Agents Chemother. 2022;66:e0207121. [DOI] [PubMed] [PMC]

44.

Pirnay J, Djebara S, Steurs G, Griselain J, Cochez C, Soir SD, et al. Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study. Nat Microbiol. 2024;9:1434–53. [DOI] [PubMed] [PMC]

45.

Gibb BP, Hadjiargyrou M. Bacteriophage therapy for bone and joint infections. Bone Joint J. 2021;103–B:234–44. [DOI] [PubMed] [PMC]

46.

Dedrick RM, Smith BE, Cristinziano M, Freeman KG, Jacobs-Sera D, Belessis Y, et al. Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease. Clin Infect Dis. 2023;76:103–12. [DOI] [PubMed] [PMC]

47.

Metsemakers W, Onsea J, Moriarty TF, Pruidze N, Nadareishvili L, Dadiani M, et al. Bacteriophage therapy for human musculoskeletal and skin/soft tissue infections. Clin Microbiol Infect. 2023;29:695–701. [DOI] [PubMed]

48.

Zalewska-Piątek B. Phage Therapy-Challenges, Opportunities and Future Prospects. Pharmaceuticals (Basel). 2023;16:1638. [DOI] [PubMed] [PMC]

49.

Suleman M, Clark JR, Bull S, Jones JD. Ethical argument for establishing good manufacturing practice for phage therapy in the UK. J Med Ethics. 2025;51:e109423. [DOI] [PubMed] [PMC]

50.

Pitashny M, Kesten I, Shlon D, Hur DB, Bar-Yoseph H. The Future of Microbiome Therapeutics. Drugs. 2025;85:117–25. [DOI] [PubMed] [PMC]

51.

Łusiak-Szelachowska M, Międzybrodzki R, Drulis-Kawa Z, Cater K, Knežević P, Winogradow C, et al. Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far. J Biomed Sci. 2022;29:23. [DOI] [PubMed] [PMC]

52.

Diallo K, Dublanchet A. Benefits of Combined Phage-Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review. Antibiotics (Basel). 2022;11:839. [DOI] [PubMed] [PMC]

53.

Li X, He Y, Wang Z, Wei J, Hu T, Si J, et al. A combination therapy of Phages and Antibiotics: Two is better than one. Int J Biol Sci. 2021;17:3573–82. [DOI] [PubMed] [PMC]

54.

Lu H, Li Z, Elbaz A, Ni S. Synergistic action of phages and lytic proteins with antibiotics: a combination strategy to target bacteria and biofilms. BMC Microbiol. 2023;23:149. [DOI] [PubMed] [PMC]

55.

Rastegar S, Skurnik M, Tadjrobehkar O, Samareh A, Samare-Najaf M, Lotfian Z, et al. Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii. BMC Infect Dis. 2024;24:1208. [DOI] [PubMed] [PMC]

56.

Ibrahim R, Aranjani JM, Valappil VK, Nair G. Unveiling the potential bacteriophage therapy: a systematic review. Future Sci OA. 2025;11:2468114. [DOI] [PubMed] [PMC]