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Drug-resistance, drug repurposing, drug repositioning, antimicrobial activity, microbial infections, treatment
Antimicrobial drug repurposing, occasionally referred to as drug repositioning or drug reprofiling, is a strategy used to find novel therapeutic uses for currently available antimicrobial medications. Repurposing currently available medications offers a viable strategy to deal with the rising antimicrobial resistance and the limited supply of innovative antimicrobial medicines that are causing this global health problem. Identifying medications with well-known safety profiles and modes of action that may be useful in treating various microbial targets or diseases . Repurposing avoids many of the early stages of drug development by making use of the substantial information and research already undertaken on existing medications, hastening the discovery of new treatment options. Additionally, by using medications with distinct mechanisms of action, repurposing may be able to overcome drug resistance. Understanding the drug's mechanism of action, conducting high-throughput screening, preclinical investigations, and clinical trials to assess efficacy and safety are often milestones in the process. There are successful cases of repurposing antimicrobial drugs, which shows the promise of this strategy to meet unmet needs in infectious diseases. Antimicrobial medication repurposing, which offers quicker and more affordable options to conventional drug development techniques, is an overall promising strategy to address antimicrobial resistance.
2. Talat, A., Bashir, Y., & Khan, A. U. (2022, February 21). Repurposing of Antibiotics: Sense or Non-sense. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.833005
3. Antibacterial products in clinical development for priority pathogens. (n.d.). Pipeline of Antibacterial Products in Clinical Development. https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/antibacterial-products-in-clinical-development-for-priority-pathogens
4. Boyd, N. K., Teng, C., & Frei, C. R. (2021, May 17). Brief Overview of Approaches and Challenges in New Antibiotic Development: A Focus On Drug Repurposing. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.684515
5. Jin, G., Wong, S. T. (2014). Toward Better Drug Repositioning: Prioritizing and Integrating Existing Methods Into Efficient Pipelines. Drug Discov.Today 19, 637–644. doi: 10.1016/j.drudis.2013.11.005
6. Strittmatter, S. M. (2014). Overcoming Drug Development Bottlenecks With Repurposing: Old Drugs Learn New Tricks. Nat. Med. 20, 590–591. doi: 10.1038/nm.3595
7. Beachy, S. H., Johnson, S. G., Olson, S., Berger, A. C. (2014). Drug Repurposing and Repositioning: Workshop Summary (Washington, D.C: The National Academies Press).
8. Hwang, T. J., Kesselheim, A. S. (2016). Leveraging Novel and Existing Pathways to Approve New Therapeutics to Treat Serious Drug-Resistant Infections. Am. J. Law Med. 42, 429–450. doi: 10.1177/0098858816658275
9. Yarchoan, R., Broder, S. (1987). Development of Antiretroviral Therapy for the Acquired Immunodeficiency Syndrome and Related Disorders. A. Prog. Rep. N. Engl. J. Med. 316, 557–564. doi: 10.1056/NEJM198702263160925
10. McBride, W. G. (1976). Studies of the Etiology of Thalidomide Dysmorphogenesis. Teratology 14, 71–87. doi: 10.1002/tera.1420140110
11. Vargesson, N. (2015). Thalidomide-Induced Teratogenesis: History and Mechanisms. Birth Defects Res. C. Embryo Today 105, 140–156. doi: 10.1002/bdrc.21096
12. Novac, N. (2013). Challenges and Opportunities of Drug Repositioning. Trends Pharmacol. Sci. 34, 267–272. doi: 10.1016/j.tips.2013.03.004
13. Fleeman, R. (2023, February 9). Repurposing inhibitors of phosphoinositide 3-kinase as adjuvant therapeutics for bacterial infections. Frontiers in Antibiotics, 2. https://doi.org/10.3389/frabi.2023.1135485
14. Koh Jing Jie, A., Hussein, M., Rao, G. G., Li, J., & Velkov, T. (2022, November 25). Drug Repurposing Approaches towards Defeating Multidrug-Resistant Gram-Negative Pathogens: Novel Polymyxin/Non-Antibiotic Combinations. Pathogens, 11(12), 1420. https://doi.org/10.3390/pathogens11121420
15. Smani, Y., & Canturri, A. M. (2023, January). Anthelmintic Drugs for Repurposing against Gram-Negative BacilliInfections. Current Medicinal Chemistry, 30(1), 59–71. https://doi.org/10.2174/0929867329666220714092916
16. Liu, Y., Tong, Z., Shi, J., Li, R., Upton, M., & Wang, Z. (2021). Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria. Theranostics, 11(10), 4910–4928. https://doi.org/10.7150/thno.56205.
17. Foletto, V. S., da Rosa, T. F., Serafin, M. B., Bottega, A., & Hörner, R. (2021, September). Repositioning of non-antibiotic drugs as an alternative to microbial resistance: a systematic review. International Journal of Antimicrobial Agents, 58(3), 106380. https://doi.org/10.1016/j.ijantimicag.2021.106380
18. Rosa, T. F. D., Machado, C. D. S., Serafin, M. B., Bottega, A., Coelho, S. S., Foletto, V. S., Rampelotto, R. F., Lorenzoni, V. V., Mainardi, A., & Hörner, R. (2021, August). Repurposing of escitalopram oxalate and clonazepam in combination with ciprofloxacin and sulfamethoxazole–trimethoprim for treatment of multidrug-resistant microorganisms and evaluation of the cleavage capacity of plasmid DNA. Canadian Journal of Microbiology, 67(8), 599–612. https://doi.org/10.1139/cjm-2020-0546
19. Gontijo, A.V.L., Pereira, S.L. & de Lacerda Bonfante, H. Can Drug Repurposing be Effective Against Carbapenem-Resistant Acinetobacter baumannii?. Curr Microbiol 79, 13 (2022). https://doi.org/10.1007/s00284-021-02693-5
20. Kapoor Y, Sharma R, Kumar A. Repurposing of Existing Drugs for the Bacterial Infections: An In silico and In vitro Study. Infect Disord Drug Targets. 2020;20(2):182-197. doi: 10.2174/1871526519666181126094244
21. Kamurai B, Mombeshora M, Mukanganyama S. Repurposing of Drugs for Antibacterial Activities on Selected ESKAPE Bacteria Staphylococcus aureus and Pseudomonas aeruginosa. Int J Microbiol. 2020 Sep 29;2020:8885338. doi: 10.1155/2020/8885338.
22. Ding, X., Yang, C., Moreira, W., Yuan, P., Periaswamy, B., Zhao, H., Tan, J., Lee, A., Ong, K. X., Park, N., Liang, Z. C., Hedrick, J. L., & Yang, Y. Y. (2020). A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics. Advanced Science, 7(17), 2001374. https://doi.org/10.1002/advs.202001374
23. An Q, Li C, Chen Y, Deng Y, Yang T, Luo Y. Repurposed drug candidates for antituberculosis therapy. Eur J Med Chem. 2020 Apr 15;192:112175. doi: 10.1016/j.ejmech.2020.112175. Epub 2020 Feb 25.
24. Cheng YS, Sun W, Xu M, Shen M, Khraiwesh M, Sciotti RJ, Zheng W. Repurposing Screen Identifies Unconventional Drugs With Activity Against Multidrug Resistant Acinetobacter baumannii. Front Cell Infect Microbiol. 2019 Jan 4;8:438. doi: 10.3389/fcimb.2018.00438.
25. Peyclit, L., Baron, S. A., & Rolain, J. M. (2019, June 11). Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria. Frontiers in Cellular and Infection Microbiology, 9. https://doi.org/10.3389/fcimb.2019.00193
26. Rana R, Sharma R, Kumar A. Repurposing of Existing Statin Drugs for Treatment of Microbial Infections: How Much Promising? Infect Disord Drug Targets. 2019;19(3):224-237. doi: 10.2174/1871526518666180806123230.
27. A. E. J. Yssel and others, Repurposing of nucleoside- and nucleobase-derivative drugs as antibiotics and biofilm inhibitors, Journal of Antimicrobial Chemotherapy, Volume 72, Issue 8, August 2017, Pages 2156–2170, https://doi.org/10.1093/jac/dkx151
28. Sharma, D., Dhuriya, Y. K., Deo, N., & Bisht, D. (2017). Repurposing and Revival of the Drugs: A New Approach to Combat the Drug Resistant Tuberculosis. Frontiers in Microbiology, 8, 315389. https://doi.org/10.3389/fmicb.2017.02452
29. Thakare R, Singh AK, Das S, Vasudevan N, Jachak GR, Reddy DS, Dasgupta A, Chopra S. Repurposing Ivacaftor for treatment of Staphylococcus aureus infections. Int J Antimicrob Agents. 2017 Sep;50(3):389-392. doi: 10.1016/j.ijantimicag.2017.03.020
30. Das, S., Dasgupta, A., & Chopra, S. (2016, August). Drug repurposing: a new front in the war against Staphylococcus aureus. Future Microbiology, 11(8), 1091–1099. https://doi.org/10.2217/fmb-2016-0021
31. Thangamani S, Mohammad H, Younis W, Seleem MN. Drug repurposing for the treatment of staphylococcal infections. Curr Pharm Des. 2015;21(16):2089-100. doi: 10.2174/1381612821666150310104416
32. Juan Carlos Palomino , Anandi Martin, Is repositioning of drugs a viable alternative in the treatment of tuberculosis?, Journal of Antimicrobial Chemotherapy, Volume 68, Issue 2, February 2013, Pages 275–283, https://doi.org/10.1093/jac/dks405
33. Chromy BA, Elsheikh M, Christensen TL, Livingston D, Petersen K, Bearinger JP, Hoeprich PD. Repurposing screens identify rifamycins as potential broad-spectrum therapy for multidrug-resistant Acinetobacter baumannii and select agent microorganisms. Future Microbiol. 2012 Aug;7(8):1011-20. doi: 10.2217/fmb.12.75.
34. Abdulaziz L, Elhadi E, Abdallah EA, Alnoor FA, Yousef BA. Antiviral Activity of Approved Antibacterial, Antifungal, Antiprotozoal and Anthelmintic Drugs: Chances for Drug Repurposing for Antiviral Drug Discovery. J Exp Pharmacol. 2022 Mar 8;14:97-115.
35. Paruchuri, S., Yetukuri, K., & Nadendla, R. (2022, August 5). Repurposing Molnupiravir as a new opportunity to treat COVID-19. Journal of Generic Medicines: The Business Journal for the Generic Medicines Sector, 18(4), 205–213. https://doi.org/10.1177/17411343221115819
36. Yacouba, A., Olowo-okere, A., & Yunusa, I. (2021, May 21). Repurposing of antibiotics for clinical management of COVID-19: a narrative review. Annals of Clinical Microbiology and Antimicrobials, 20(1). https://doi.org/10.1186/s12941-021-00444-9
37. Monalis, H., Sujith, R., Leela, K. V., & Balamurali, V. (2020). Antibiotics in Combination with Antifungals to Combat Drug Resistant Candida – A Concept on Drug Repurposing. Journal of Advances in Microbiology, 20(8), 42–48. https://doi.org/10.9734/jamb/2020/v20i830274
38. Capoci, I. R. G., Faria, D. R., Sakita, K. M., Rodrigues-Vendramini, F. A. V., Bonfim-Mendonça, P. D. S., Becker, T. C. A., Kioshima, R. S., Svidzinski, T. I. E., & Maigret, B. (2019, March). Repurposing approach identifies new treatment options for invasive fungal disease. Bioorganic Chemistry, 84, 87–97. https://doi.org/10.1016/j.bioorg.2018.11.019
39. Shirley DA, Sharma I, Warren CA, Moonah S. Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent. Front Cell Infect Microbiol. 2021 Mar 11;11:633194. doi: 10.3389/fcimb.2021.633194
40. Shirley, D. A., & Moonah, S. (2021, March 11). Repurposing FDA-approved drug disulfiram plus zinc supplement for treatment of parasitic infections. https://doi.org/10.22541/au.161548505.58364479/v1
41. Anwar, A., Khan, N. A., & Siddiqui, R. (2020, February 19). Repurposing of Drugs Is a Viable Approach to Develop Therapeutic Strategies against Central Nervous System Related Pathogenic Amoebae. ACS Chemical Neuroscience, 11(16), 2378–2384. https://doi.org/10.1021/acschemneuro.9b00613
42. Laudisi F, Marônek M, Di Grazia A, Monteleone G, Stolfi C. Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System. Int J Mol Sci. 2020 Jul 13;21(14):4957. doi: 10.3390/ijms21144957.
43. Czaplewski, L., Bax, R., Clokie, M., Dawson, M., Fairhead, H., Fischetti, V. A.,etal. (2016, February). Alternatives to antibiotics—a pipeline portfolio review. The Lancet Infectious Diseases, 16(2), 239–251. https://doi.org/10.1016/s1473-3099(15)00466-1