Investigation of the effectiveness of metformin and various antibiotic combinations against Pseudomonas aeruginosa isolate
Keywords:
antibiotic resistance, AMR, chequerboard, metformin, pseudomonas aeruginosa, synergyAbstract
Background and aim: Pseudomonas aeruginosa infections are the focus of new treatment alternatives due to their frequent development of resistance to antibiotics and formation of biofilms. Recently, emphasis has been placed on combinations of antibiotics with drugs used for different indications. In this study the combined effects of metformin with imipenem, ceftazidime, cefepim, ciprofloxacin and levofloxacin has been investigated.
Methods: 50 P. aeruginosa isolates isolated from patients with cystic fibrosis come to Gaziantep University Microbiology Laboratory were included in the study. The susceptibilities of the isolates to antibiotics were investigated by the liquid microdilution method and the combined effect of metformin and antibiotics by the chequerboard synergy test.
Results: In our study, as a result of the chequerboard synergy test; synergy between ceftazidime and metformin 6%, partial synergistic 22% isolates; while no synergistic effect was detected between cefepim and metformin in any isolate, partially synergy 46%; synergy between imipenem and metformin 4%, partial synergy 10%; synergy between ciprofloxacin and metformin 6%, partial synergy 6%, antagonist effect 2%; synergy was detected between levofloxacin and metformin 2% and a partial synergy was detected 12%.
Conclusions: This study shows that metformin could be a potential antibiotic in its current form or in different chemical forms to be produced synthetically.
References
1. Brindhadevi K, LewisOscar F, Mylonakis E, Shanmugam S, Verma TN, Pugazhendhi A. Biofilm and quorum sensing mediated pathogenicity in Pseudomonas aeruginosa. Process Biochem 2020;96:49-57. doi: 10.1016/j.procbio.2020.06.001
2. Chadha J, Harjai K, Chhibber S. Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing. Environ Microbiol 2022;24(6):2630-56. doi: 10.1111/1462-2920.15784
3. Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit: a critical review. Genes Dis 2019;6(2):109-19. doi: 10.1016/j.gendis.2019.04.001
4. Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019;37(1):177-92. doi: 10.1016/j.biotechadv.2018.11.013
5. Glen KA, Lamont IL. β-lactam resistance in Pseudomonas aeruginosa: current status, future prospects. Pathogens 2021;10(12):1638. doi: 10.3390/pathogens10121638
6. Zhao L, Wang S, Li X, He X, Jian L. Development of in vitro resistance to fluoroquinolones in Pseudomonas aeruginosa. Antimicrob Resist Infect Control 2020;9(1):1-8. doi: 10.1186/s13756-020-00793-8
7. Thacharodi A, Lamont IL. Aminoglycoside-modifying enzymes are sufficient to make Pseudomonas aeruginosa clinically resistant to key antibiotics. Antibiotics 2022;11(7):884. doi: 10.3390/antibiotics11070884
8. Reynolds D, Kollef M. The epidemiology and pathogenesis and treatment of Pseudomonas aeruginosa infections: an update. Drugs 2021;81(18):2117-31. doi: 10.1007/s40265-021-01635-6
9. Horcajada JP, Montero M, Oliver A, et al. Epidemiology and treatment of multi-drug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections. Clin Microbiol Rev 2019;32(4):e00031-19. doi: 10.1128/cmr.00031-19
10. Moya B, Dötsch A, Juan C, et al. β-lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein. PLoS Pathog 2009;5(3):e1000353. doi: 10.1371/journal.ppat.1000353
11. Masadeh MM, Alzoubi KH, Masadeh MM, Aburashed ZO. Metformin as a potential adjuvant antimicrobial agent against multidrug resistant bacteria. Clin Pharmacol Adv Appl 2021;13:83-90. doi: 10.2147/cpaa.s297903
12. Opal SM. Non-antibiotic treatments for bacterial diseases in an era of progressive antibiotic resistance. Springer 2016;1-3. doi: 10.1186/s13054-016-1549-1
13. Dastidar SG, Saha P, Sanyamat B, Chakrabarty A. Antibacterial activity of ambodryl and benadryl. J Appl Bacteriol 1976;41(2):209-14. doi: 10.1111/j.1365-2672.1976.tb00621.x
14. Duncan AI, Koch CG, Xu M, et al. Recent metformin ingestion does not increase in-hospital morbidity or mortality after cardiac surgery. Anesth Analg 2007;104(1):42-50. doi: 10.1213/01.ane.0000242532.42656.e7
15. Wu X, Fan W, Fan B. Synergistic effects of silver ions and metformin against Enterococcus faecalis under high-glucose conditions in vitro. BMC Microbiol 2021;21(1):1-9. doi: 10.1186/s12866-021-02291-2
16. Liu Y, Jia Y, Yang K, et al. Metformin restores tetracyclines susceptibility against multidrug resistant bacteria. Adv Sci 2020;7(12):1902227. doi: 10.1002/advs.201902227
17. He X, Jin S, Fan W, Fan B. Synergistic in vitro antimicrobial activity of Triton X-100 and metformin against Enterococcus faecalis in normal and high-glucose conditions. Microorganisms 2022;10(1):124. doi: 10.3390/microorganisms10010124
18. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 13.1. 2023. http://www.eucast.org
19. Adaleti R, Nakipoğlu Y, Arıcı N, et al. Evaluation of in vitro efficacy of meropenem/colistin and meropenem/fosfomycin combinations on multidrug resistant Gram-negative bacilli. Mikrobiyol Bul 2023;57(3):365-77. doi: 10.5578/mb.20239930
20. Defoirdt T. Quorum-sensing systems as targets for antivirulence therapy. Trends Microbiol 2018;26(4):313-28. doi: 10.1016/j.tim.2017.10.005
21. Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health 2015;109(7):309-18. doi: 10.1179/2047773215y.0000000030
22. Zuo J, Shen Y, Wang H, et al. Effects of metformin on Streptococcus suis LuxS/AI-2 quorum sensing system and biofilm formation. Microb Pathog 2023;106183. doi: 10.1016/j.micpath.2023.106183
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Kaan Çeylan, Yasemin Zer, Gülsüm Kaya Özen, Esra Kırkgöz Karabulut

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

