Bacteriophage Therapy Against Antimicrobial Resistant Crisis


  • Fahim Ullah Department of Microbiology, Abbotabad University of Science and Technology
  • Syed Sohail Ahmad Department of Medical Laboratory Technology, Khyber Pakhtunkhwa Institute of Medical Sciences
  • Mazhar Ali Khan Department of Microbiology, Hazara University Mansehra
  • Sarwat Moon Indus Hospital and Health Network



Antibiotic Resistance, Phage Replication Mechanisms, Bacteriophage Therapy, Phage Therapy Safety and Specificity., Antimicrobial Resistance Crisis


The most common virus on the earth is bacteriophage (or phages) that are present in all organisms. Their classification is currently being evaluated based on the phage's unique and antibacterial properties. The phage replicates within the host through a lytic or lysogenic process following infection and use of a bacterial cell machine. Phage has become an effective therapeutic drug against pathogens after twort and Filex d'Herelle discovery of bacteriophage in the 1900s, and subsequent research has been conducted. Nevertheless, bacteriophage therapy has become an unavoidable option for research due to the recent occurrence of bacterial antibiotics resistance. Around fifty years after antibiotic were found, antibiotics resistance is key risk for health care. Antimicrobial resistance is a rising big issue in global healthcare. The WHO, 1st report on antimicrobial resistances globally, has emphasized the threat of a forthcoming post antibiotics age, where little infection could be not treatable and once again will be fatal. Considering the present condition, producing therapeutic agent that are complementary to antibiotics play great role to fight against antibiotic resistance. The crisis requires development and implementation of new therapeutic agents against infections and phage therapy is suitable to control infectious diseases because safety of phage therapy. There is a perception with regards to phage therapy that phages are usually safe, on the bases of fact that they are ubiquitous in nature and our continued contact to phages in the environment and furthermore that they are widely used without adverse effects in many of the world. with this positive interpretation, the application of phage therapy must be verified by current research studies. bacteriophage preparations contain detrimental substances, such as toxins of gram-negative bacteria, during the formulation process of bacteriophage and that can be remove by different purification methods. Phages effects normal flora GIT negligibly due to specificity in nature and they infect only a small number of bacterial species.


Download data is not yet available.


Abedon, S. (2017). Bacteriophage clinical use as antibacterial “drugs”: utility and precedent. Microbiol. Spectr. 5: BAD-0003-2016. doi: 10.1128/microbiolspec. Retrieved from DOI:

Abedon, S. T. (2017). Information phage therapy research should report. Pharmaceuticals, 10(2), 43. DOI:

Abedon, S. T. (2018). Phage therapy: Various perspectives on how to improve the art. In Host-Pathogen Interactions (pp. 113-127): Springer. DOI:

Abedon, S. T., Kuhl, S. J., Blasdel, B. G., & Kutter, E. M. (2011). Phage treatment of human infections. Bacteriophage, 1(2), 66-85. DOI:

Abedon, S. T., & Thomas-Abedon, C. (2010). Phage therapy pharmacology. Current pharmaceutical biotechnology, 11(1), 28-47. DOI:

Alisky, J., Iczkowski, K., Rapoport, A., & Troitsky, N. (1998). Bacteriophages show promise as antimicrobial agents. Journal of Infection, 36(1), 5-15. DOI:

Altamirano, F. L. G., & Barr, J. J. (2019). Phage therapy in the postantibiotic era. Clinical microbiology reviews, 32(2). DOI:

Aslanov, B., Lubimova, A., Dolgiy, A., & Pshenichnaya, N. (2018). Bacteriophages for the control of Klebsiella outbreak in the neonatal intensive care unit. International Journal of Infectious Diseases, 73, 295. DOI:

Azeredo, J., & Sillankorva, S. (2018). Bacteriophage Therapy: Springer. DOI:

Barrow, P. A., & Soothill, J. S. (1997). Bacteriophage therapy and prophylaxis: rediscovery and renewed assessment of potential. Trends in microbiology, 5(7), 268-271. DOI:

Bruynoghe, R., & Maisin, J. (1921). Essais de thérapeutique au moyen du bacteriophage. CR Soc Biol, 85, 1120-1121.

Campbell, A. (2003). The future of bacteriophage biology. Nature Reviews Genetics, 4(6), 471-477. DOI:

Chan, B. K., Abedon, S. T., & Loc-Carrillo, C. (2013). Phage cocktails and the future of phage therapy. Future microbiology, 8(6), 769-783. DOI:

Cisek, A. A., Dąbrowska, I., Gregorczyk, K. P., & Wyżewski, Z. (2017). Phage therapy in bacterial infections treatment: one hundred years after the discovery of bacteriophages. Current microbiology, 74(2), 277-283. DOI:

Clark, J. R. (2015). Bacteriophage therapy: history and future prospects. Future Virology, 10(4), 449-461. DOI:

Czaplewski, L., Bax, R., Clokie, M., Dawson, M., Fairhead, H., Fischetti, V. A., . . . Harper, D. Alternatives to antibiotics–a pipeline portfolio.

D’Costa, V., & King, C. (2011). Kalan, l. Morar, M., Sung, WWL, Schwarz, C., Froese, D., Zazula, G., Calmels, F., Debruyne, R., Golding, GB, Poinar, HN & Wright, GD, 457-461. DOI:

Dalmasso, M., Hill, C., & Ross, R. P. (2014). Exploiting gut bacteriophages for human health. Trends in microbiology, 22(7), 399-405. DOI:

de Jonge, P. A., Nobrega, F. L., Brouns, S. J., & Dutilh, B. E. (2019). Molecular and evolutionary determinants of bacteriophage host range. Trends in microbiology, 27(1), 51-63. DOI:

Ding, C., & He, J. (2010). Effect of antibiotics in the environment on microbial populations. Applied Microbiology and Biotechnology, 87(3), 925-941. DOI:

Dondorp, A. M., Fairhurst, R. M., Slutsker, L., MacArthur, J. R., MD, J. G. B., Guerin, P. J., . . . Plowe, C. V. (2011). The threat of artemisinin-resistant malaria. New England Journal of Medicine, 365(12), 1073-1075. DOI:

Duckworth, D. H. (1976). " Who discovered bacteriophage?". Bacteriological reviews, 40(4), 793. DOI:

Dufour, N., Delattre, R., Ricard, J.-D., & Debarbieux, L. (2017). The lysis of pathogenic Escherichia coli by bacteriophages releases less endotoxin than by β-lactams. Clinical infectious diseases, 64(11), 1582-1588. DOI:

Fadlallah, A., Chelala, E., & Legeais, J.-M. (2015). Corneal infection therapy with topical bacteriophage administration. The open ophthalmology journal, 9, 167. DOI:

Fauconnier, A. (2018). Guidelines for bacteriophage product certification. In Bacteriophage Therapy (pp. 253-268): Springer. DOI:

Fish, R., Kutter, E., Wheat, G., Blasdel, B., Kutateladze, M., & Kuhl, S. (2016). Bacteriophage treatment of intransigent diabetic toe ulcers: a case series. Journal of wound care, 25(Sup7), S27-S33. DOI:

Gill, J. J., & Hyman, P. (2010). Phage choice, isolation, and preparation for phage therapy. Current pharmaceutical biotechnology, 11(1), 2-14. DOI:

Goodridge, L. D. (2010). Designing phage therapeutics. Current pharmaceutical biotechnology, 11(1), 15-27. DOI:

Green, J. L., Holmes, A. J., Westoby, M., Oliver, I., Briscoe, D., Dangerfield, M., . . . Beattie, A. J. (2004). Spatial scaling of microbial eukaryote diversity. Nature, 432(7018), 747-750. DOI:

Harper, D. R. (2018). Criteria for selecting suitable infectious diseases for phage therapy. Viruses, 10(4), 177. DOI:

Henein, A. (2013). What are the limitations on the wider therapeutic use of phage? Bacteriophage, 3(2), e24872. DOI:

Kakasis, A., & Panitsa, G. (2019). Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review. International journal of antimicrobial agents, 53(1), 16-21. DOI:

Keen, E. C. (2015). A century of phage research: bacteriophages and the shaping of modern biology. Bioessays, 37(1), 6-9. DOI:

Kortright, K. E., Chan, B. K., Koff, J. L., & Turner, P. E. (2019). Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell host & microbe, 25(2), 219-232. DOI:

Kramberger, P., Honour, R. C., Herman, R. E., Smrekar, F., & Peterka, M. (2010). Purification of the Staphylococcus aureus bacteriophages VDX-10 on methacrylate monoliths. Journal of virological methods, 166(1-2), 60-64. DOI:

Krylov, V. (2001). Phagotherapy in terms of bacteriophage genetics: hopes, perspectives, safety, limitations. Genetika, 37(7), 869. DOI:

Kutateladze, M., & Adamia, R. (2010). Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends in biotechnology, 28(12), 591-595. DOI:

Kutter, E., De Vos, D., Gvasalia, G., Alavidze, Z., Gogokhia, L., Kuhl, S., & Abedon, S. (2010). Bacteriophage therapy of venous leg ulcers in humans: Results of a phase I safety trial. Curr. Pharm. Biotechnol, 11, 69-86.

Kutter, E., De Vos, D., Gvasalia, G., Alavidze, Z., Gogokhia, L., Kuhl, S., & Abedon, S. T. (2010). Phage therapy in clinical practice: treatment of human infections. Current pharmaceutical biotechnology, 11(1), 69-86. DOI:

Kutter, E., & Sulakvelidze, A. (2004). Bacteriophages: biology and applications: Crc press. DOI:

Latz, S., Wahida, A., Arif, A., Häfner, H., Hoß, M., Ritter, K., & Horz, H. P. (2016). Preliminary survey of local bacteriophages with lytic activity against multi‐drug resistant bacteria. Journal of basic microbiology, 56(10), 1117-1123. DOI:

Lehmann, P. F. (1999). PR Murray, EJ Baron, MA Pfaller, FC Tenover and RH Yolken, eds. Manual of Clinical Microbiology. Mycopathologia, 146(2), 107. DOI:

Letkiewicz, S., Międzybrodzki, R., Fortuna, W., Weber-Dąbrowska, B., & Górski, A. (2009). Eradication of Enterococcus faecalis by phage therapy in chronic bacterial prostatitis—case report. Folia microbiologica, 54(5), 457. DOI:

Loc-Carrillo, C., & Abedon, S. T. (2011). Pros and cons of phage therapy. Bacteriophage, 1(2), 111-114. DOI:

Malik, D. J., Sokolov, I. J., Vinner, G. K., Mancuso, F., Cinquerrui, S., Vladisavljevic, G. T., . . . Kirpichnikova, A. (2017). Formulation, stabilisation and encapsulation of bacteriophage for phage therapy. Advances in colloid and interface science, 249, 100-133. DOI:

Mattila, S., Ruotsalainen, P., & Jalasvuori, M. (2015). On-demand isolation of bacteriophages against drug-resistant bacteria for personalized phage therapy. Frontiers in microbiology, 6, 1271. DOI:

Mazel, D. (2004). Integrons and the origin of antibiotic resistance gene cassettes. ASM News-American Society for Microbiology, 70, 520-525.

Merabishvili, M., Pirnay, J.-P., Verbeken, G., Chanishvili, N., Tediashvili, M., Lashkhi, N., . . . Van Parys, L. (2009). Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PloS one, 4(3), e4944. DOI:

Merril, C. R., Biswas, B., Carlton, R., Jensen, N. C., Creed, G. J., Zullo, S., & Adhya, S. (1996). Long-circulating bacteriophage as antibacterial agents. Proceedings of the National Academy of Sciences, 93(8), 3188-3192. DOI:

Michael, C. A., Dominey-Howes, D., & Labbate, M. (2014). The antimicrobial resistance crisis: causes, consequences, and management. Frontiers in public health, 2, 145. DOI:

Millard, A. D., Clokie, M. R., Letarov, A. V., & Heaphy, S. (2011). Phages in nature. Bacteriophage, 1, 31-45. DOI:

Moellering Jr, R. C. (2011). Discovering new antimicrobial agents. International journal of antimicrobial agents, 37(1), 2-9. DOI:

Monsur, K., Rahman, M., Huq, F., Islam, M., Northrup, R., & Hirschhorn, N. (1970). Effect of massive doses of bacteriophage on excretion of vibrios, duration of diarrhoea and output of stools in acute cases of cholera. Bulletin of the World Health Organization, 42(5), 723.

Nelson, D. C., Schmelcher, M., Rodriguez-Rubio, L., Klumpp, J., Pritchard, D. G., Dong, S., & Donovan, D. M. (2012). Endolysins as antimicrobials. In Advances in virus research (Vol. 83, pp. 299-365): Elsevier. DOI:

Nir-Paz, R., Gelman, D., Khouri, A., Sisson, B. M., Fackler, J., Alkalay-Oren, S., . . . Bader, R. (2019). Successful treatment of antibiotic-resistant, poly-microbial bone infection with bacteriophages and antibiotics combination. Clinical infectious diseases, 69(11), 2015-2018. DOI:

Parracho, H. M., Burrowes, B. H., Enright, M. C., McConville, M. L., & Harper, D. R. (2012). The role of regulated clinical trials in the development of bacteriophage therapeutics. Journal of molecular and genetic medicine: an international journal of biomedical research, 6, 279. DOI:

Payne, R. J., & Jansen, V. A. (2000). Phage therapy: the peculiar kinetics of self‐replicating pharmaceuticals. Clinical pharmacology & therapeutics, 68(3), 225-230. DOI:

Payne, R. J., & Jansen, V. A. (2003). Pharmacokinetic principles of bacteriophage therapy. Clinical pharmacokinetics, 42(4), 315-325. DOI:

Pires, D. P., Cleto, S., Sillankorva, S., Azeredo, J., & Lu, T. K. (2016). Genetically engineered phages: a review of advances over the last decade. Microbiology and Molecular Biology Reviews, 80(3), 523-543. DOI:

Pirnay, J.-P., Blasdel, B. G., Bretaudeau, L., Buckling, A., Chanishvili, N., Clark, J. R., . . . De Vos, D. (2015). Quality and safety requirements for sustainable phage therapy products. Pharmaceutical research, 32(7), 2173-2179. DOI:

Pirnay, J.-P., Merabishvili, M., Van Raemdonck, H., De Vos, D., & Verbeken, G. (2018). Bacteriophage production in compliance with regulatory requirements. In Bacteriophage therapy (pp. 233-252): Springer. DOI:

Prevention, E. C. f. D., & Control. (2016). Summary of the latest data on antibiotic resistance in the European Union. In: ECDC Stockholm.

Projan, S. J. (2003). Why is big Pharma getting out of antibacterial drug discovery? Current opinion in microbiology, 6(5), 427-430. DOI:

Rashmi, S., Chaman, L., & Bhuvneshwar, K. (2005). Antibacterial resistance: current problems and possible solutions. Indian J. Med. Sci, 59, 120-129. DOI:

Rhoads, D., Wolcott, R., Kuskowski, M., Wolcott, B., Ward, L., & Sulakvelidze, A. (2009). Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. Journal of wound care, 18(6), 237-243. DOI:

Samsygina, G., & Boni, E. (1984). Bacteriophages and phage therapy in pediatric practice. Pediatriia(4), 67.

Sharp, R. (2001). Bacteriophages: biology and history. Journal of Chemical Technology & Biotechnology, 76(7), 667-672. DOI:

Skurnik, M., Pajunen, M., & Kiljunen, S. (2007). Biotechnological challenges of phage therapy. Biotechnology letters, 29(7), 995-1003. DOI:

Speck, P., & Smithyman, A. (2016). Safety and efficacy of phage therapy via the intravenous route. FEMS microbiology letters, 363(3). DOI:

Sulakvelidze, A., Alavidze, Z., & Morris, J. G. (2001). Bacteriophage therapy. Antimicrobial agents and chemotherapy, 45(3), 649-659. DOI:

Sulakvelidze, A., & Barrow, P. (2005). Phage therapy in animals and agribusiness. Bacteriophages: biology and applications, 335-380. DOI:

Summers, W. C. (1999). Felix dHerelle and the origins of molecular biology: Yale University Press.

Sykes, R. (2010). The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective. Journal of Antimicrobial Chemotherapy, 65(9), 1842-1852. DOI:

Twort, F. (1920). Researches on dysentery. British journal of experimental pathology, 1(5), 237.

Van Helvoort, T. (1992). Bacteriological and physiological research styles in the early controversy on the nature of the bacteriophage phenomenon. Medical History, 36(3), 243-270. DOI:

Vandenheuvel, D., Lavigne, R., & Brüssow, H. (2015). Bacteriophage therapy: advances in formulation strategies and human clinical trials. Annual review of virology, 2, 599-618. DOI:

Viertel, T. M., Ritter, K., & Horz, H.-P. (2014). Viruses versus bacteria—novel approaches to phage therapy as a tool against multidrug-resistant pathogens. Journal of Antimicrobial Chemotherapy, 69(9), 2326-2336. DOI:

Villarroel, J., Larsen, M. V., Kilstrup, M., & Nielsen, M. (2017). Metagenomic analysis of therapeutic PYO phage cocktails from 1997 to 2014. Viruses, 9(11), 328. DOI:

Weber-Dąbrowska, B., Jończyk-Matysiak, E., Żaczek, M., Łobocka, M., Łusiak-Szelachowska, M., & Górski, A. (2016). Bacteriophage procurement for therapeutic purposes. Frontiers in microbiology, 7, 1177. DOI:

Whitman, W. B., Coleman, D. C., & Wiebe, W. J. (1998). Prokaryotes: the unseen majority. Proceedings of the National Academy of Sciences, 95(12), 6578-6583. DOI:

Wright, A., Hawkins, C., Änggård, E., & Harper, D. (2009). A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic‐resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clinical otolaryngology, 34(4), 349-357. DOI:




How to Cite

Ullah, F., Ahmad, S. S., Khan, M. A., & Moon, S. (2023). Bacteriophage Therapy Against Antimicrobial Resistant Crisis. Journal of Health Science and Medical Therapy, 2(01), 1–18.