Published September 12, 2025 | Version v1

Theoretical and experimental investigation of antibacterial activity of lidocaine hydrochloride against clinical resistant gram-negative strains of bacteria

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Introduction. Today, antimicrobial resistance is the number one problem worldwide. One of the first mentions of the emergence of antibiotic-resistant strains of bacteria in humans was obtained during military conflicts in Iraq and Afghanistan 20 years ago. In addition, according to the latest data, it has found that Acinetobacter baumani, Pseudomonas aeruginosa, Klebsiela pneumonia and Enterococcus cloacae are predominant among all isolated resistant pathogens. So, the search of new antibacterial drug that can deal with antimicrobial resistance is a task number one. The purpose of the study was to investigate in vitro and in silico antibacterial activity against clinical multidrug-resistant strains of Staphylococcus aureus, P. aeruginosa, A. baumannii, K. pneumonia and E. cloacae. Materials and methods. The object of the study was lidocaine hydrochloride. The molecular docking was performed using AutoDockTools 1.5.6; antibacterial effects were evaluated by the well and "dilution" methods method. Isolates were obtained from clinical samples including tracheal aspirate and broncoalveolar lavage. Results. Lidocaine hydrochloride was shown high selectivity to AHS LasI, Experimental research was demonstrated that against resistant strain of P. aeruginosa lidocaine hydrochloride inhibited growth – from 23.0±0.2 to 16.0±0.2 mm, against A. baumannii – from 24.0±0.1 to 16.0±0.1 mm, against E. cloacea – from 18.0±0.2 to 16.0±0.2 mm, K. pneumonia – from 21.0±0.2 to 16.0±0.2 mm, respectively. The minimum inhibitory concentration (MIC) values of lidocaine hydrochloride for P. aeruginosa, E. cloacea, A. baumannii, K. pneumonia was 0.00075 mmol/L. Conclusion. It has conducted theoretical and experimental studies of antibacterial effect of lidocaine hydrochloride. The theoretical results demonstrated that lidocaine hydrochloride highly selectively inhibited only one enzyme – AHS LasI. According to experimental results, it was shown that lidocaine hydrochloride effectively inhibited resistant strains of P. aeruginosa, E. cloacea, A. baumannii, K. pneumonia. So, lidocaine hydrochloride is a perspective substance for elimination resistance of antibiotics.

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References

  • 1. Walsh TR, Gales AC, Laxminarayan R, Dodd PC. Antimicrobial Resistance: Addressing a Global Threat to Humanity. PLOS Med. 2023;20(7):e1004264. DOI: https://doi.org/10.1371/journal.pmed.1004264
  • 2. Mende K, Akers KS, Tyner SD, Bennett JW, Simons MP, Blyth DM, Li P, Stewart L, Tribble DR. Multidrug-Resistant and Virulent Organisms Trauma Infections: Trauma Infectious Disease Outcomes Study Initiative. Mil Med. 2022; 187(Supplement_2):42-51. DOI: https://doi.org/10.1093/milmed/usab131
  • 3. Kalpana S, Lin WY, Wang YC, Fu Y, Lakshmi A, Wang HY. Antibiotic Resistance Diagnosis in ESKAPE Pathogens—A Review on Proteomic Perspective. Diagnostics. 2023;13(6):1014. DOI: https://doi.org/10.3390/diagnostics13061014
  • 4. Karnina R, Arif SK, Hatta M, Bukhari A. Molecular mechanisms of lidocaine. Ann Med Surg. 2021;69:102733. DOI: https://doi.org/10.1016/j.amsu.2021.102733
  • 5. Caracas HC, Maciel JV, Martins PM, de Souza MM, Maia LC. The use of lidocaine as an anti-inflammatory substance: A systematic review. J Dent. 2009;37(2):93-7. DOI: https://doi.org/10.1016/j.jdent.2008.10.005
  • 6. Razavi BM, Fazly Bazzaz BS. A review and new insights to antimicrobial action of local anesthetics. Eur J Clin Microbiol Amp Infect Dis. 2019;38(6):991-1002. DOI: https://doi.org/10.1007/s10096-018-03460-4
  • 7. Heller S, Seemann RJ, Burgkart R, Obermeier A, Locher H. Lidocaine Shows Significant Antimicrobial Effects Against Staphylococcus Species: An In-Vitro Study Comparing Different Combinations of Lidocaine and Clinically Used Injectables, like Steroids and Hyaluronan, in the Context of Arthritis Management. Biomedicines. 2025;13(1):106. DOI: https://doi.org/10.3390/biomedicines13010106
  • 8. Palmeira-de-Oliveira A, Ramos AR, Gaspar C, Palmeira-de-Oliveira R, Gouveia P, Martinez-de-Oliveira J. In VitroAnti-CandidaActivity of Lidocaine and Nitroglycerin: Alone and Combined. Infect Dis Obstet Gynecol. 2012;2012:1-4. DOI: https://doi.org/10.1155/2012/727248
  • 9. Mbarga MJ, Podoprigora IV, Volina EG, Ermolaev AV, Smolyakova LA. Evaluation of Changes Induced in the Probiotic Escherichia coli M17 Following Recurrent Exposure to Antimicrobials. J Pharm Res Int. 2021:158-67. DOI: https://doi.org/10.9734/jpri/2021/v33i29b31601
  • 10. Maslov O, Komisarenko M, Ponomarenko S,Horopashna D, Osolodchenko T, Kolisnyk S,Derymedvid L, Shovkova Z, Akhmedov E.Investigation the influence of biologically activecompounds on the antioxidant, antibacterial and anti-inflammatory activities of red raspberry (Rubus idaeous L.) leaf extract. Curr Issues Pharm Med Sci.2022;35(4):229-35. DOI: https://doi.org/10.2478/cipms-2022-0040
  • 11. Morris GM, Huey R, Olson AJ. Using AutoDock for Ligand‐Receptor Docking. Curr Protoc Bioinform.2008;24(1):1-10. DOI: https://doi.org/10.1002/0471250953.bi0814s24
  • 12. RCSB PDB: Homepage. RCSB PDB: Homepage. Available from: https://www.rcsb.org/.
  • 13. PubChem. PubChem;. Available from: https://pubchem.ncbi.nlm.nih.gov/.
  • 14. CASTp 3.0: Computed Atlas of Surface Topography of proteins; Available from: http://sts.bioe.uic.edu/castp/index.html?201l
  • 15. Kondža M, Brizić I, Jokić S. Flavonoids as CYP3A4Inhibitors In Vitro. Biomedicines. 2024;12(3):644.DOI: https://doi.org/10.3390/biomedicines12030644
  • 16. Jadhav AK, Karuppayil SM. Molecular dockingstudies on thirteen fluoroquinolines with humantopoisomerase II a and b. Silico Pharmacol.2017;5(1):22-3. DOI: https://doi.org/10.1007/s40203-017-0024-2
  • 17. Mbarga MJ, Podoprigora IV, Volina EG,Ermolaev AV, Smolyakova LA. Evaluation of ChangesInduced in the Probiotic Escherichia coli M17Following Recurrent Exposure to Antimicrobials. JPharm Res Int. 2021:158-67.DOI: https://doi.org/10.9734/jpri/2021/v33i29b31601
  • 18. Rahman M, Browne JJ, Van Crugten J, Hasan MF,Liu L, Barkla BJ. In Silico, Molecular Docking and In Vitro Antimicrobial Activity of the Major Rapeseed Seed Storage Proteins. Front Pharmacol. 2020;11:22-40.DOI: https://doi.org/10.3389/fphar.2020.01340
  • 19. Zuo K, Liang L, Du W, Sun X, Liu W, Gou X,Wan H, Hu J. 3D-QSAR, Molecular Docking andMolecular Dynamics Simulation of Pseudomonas aeruginosa LpxC Inhibitors. Int J Mol Sci.2017;18(5):761.DOI: https://doi.org/10.3390/ijms18050761
  • 20. Abinaya M, Gayathri M. Inhibition of biofilm formation, quorum sensing activity and molecular docking study of isolated 3, 5, 7-Trihydroxyflavone from Alstonia scholaris leaf against P.aeruginosa. Bioorganic Chem. 2019;87:291-301. DOI: https://doi.org/10.1016/j.bioorg.2019.03.050