Antimicrobial and antiviral activity of three-component complex of chlorhexidine-EDTA-zinc

Chlorhexidine bigluconate (CНX) is widely used as a disinfectant, but it is not effective against spore-forming microorganisms, as well as viruses. In this work, a method has been found to increase the biocidal activity of chlorhexidine by using it as part of a complex including ethylenediaminetetraacetic acid (EDTA) and zinc chloride. The structure of the three-component complex СНX-EDTA-zinc is proved by the MALDI-MS method. The biocidal activity of the chlorhexidine complex has been studied in vitro and in vivo experiments. It is shown that the complex is significantly superior to chlorhexidine alone, both in terms of activity level and in the breadth of biocidal action. In relation to the studied bacterial and fungal strains, the СНX-EDTA-Zn complex was 4–5 times more active than chlorhexidine bigluconate. In concentrations from 1.0 mg/ml to 0.008 mg/ml (depending on the type of micro-organism), in vitro the complex showed both bacteriostatic and bactericidal effects against the main pathogens of bacterial diseases of birds. In clinical conditions, the complex has shown high efficiency in the treatment of dermatitis in small domestic and farm animals. Also, in vitro and in vivo, the complex showed unexpectedly high antitubercular activity comparable to that of monofloxacin, including on drug-resistant strains of mycobacteria. in vitro experiments involving polio virus and adenovirus have shown that the СHX-EDTA-Zn complex possesses virulent action.

1. Kvashnina DV, Kovalishena OV. Ocenka primenenija hlorgeksidina kak antisepticheskogo sredstva. Medicinskij al'manah. 2016; 43 (3): 62–66. Russian.

2. Zverkov AV, Zuzova AP. Hlorgeksidin: proshloe, nastojashhee i budushhee odnogo iz osnovnyh antiseptikov. Antimikrobnye preparaty. 2013; 15 (4): 279–85. Russian.

3. Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005; 99: 703–15.

4. Hugo WB. Disinfection mechanisms. In: Russell AD, Hugo WB, Ayliffe GAJ, eds. Principles and practice of disinfection, preservation and sterilization. Oxford: Blackwell, 1992; p. 187–210.

5. Mashkovskij MD. Lekarstvennye sredstva. M.: Novaja Volna, 2006. Russian.

6. Jones CG. Chlorhexidine: is it still the gold standard? Periodontol. 1997; 15: 55–62.

7. Junco-Lafuente MP, Baca-García P, Mesa-Aguado FL. Utilización de la clorhexidina en la prevención oral de pacientes de la tercera edad. Revista del Ilustre Consejo General de Colegios de Odontólogos y Estomatólogos de España. 2001; 6: 81–89.

8. Carrouel F, Conte MP, Fisher J, Gonçalves LS, Dussart С, Llodra JC, Bourgeois D. COVID-19: A Recommendation to Examine the Effect of Mouthrinses With β-Cyclodextrin Combined With Citrox in Preventing Infection and Progression. J Clin Med. 2020; 9 (4): 1126.

9. Wand ME, Bock LJ, Bonney LC, Sutton JM. Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine. Antimicrob. Agents Chemother. 2017; 61 (1): 1162–16.

10. Gupta M, Mahajan V, Mehta K, Chauhan P. Zinc Therapy in dermatology: a review. Dermatology Research and Practice. 2014; 9. Available from: https://www.hindawi.com/journals/drp/2014/709152/.

11. Djatlova NM, Temkina VYa, Popov KI. Kompleksony i kompleksonaty metallov. M.: Himija, 1988; 544 s. Russian.

12. Metody laboratornyh issledovanij i ispytanij medikoprofilakticheskih dezinfekcionnyh sredstv dlja ocenki ih jeffektivnosti i bezopasnosti: Rukovodstvo. M.: Federal'nyj centr gigieny i jepidemiologii Rospotrebnadzora, 2010; 615 s. Russian.

13. Palomino J-C, Martin A, Camacho M, Guerra H, Swings J, Portaels F. ResazurinMicrotitre Assay Plate — Simple and Inexpensive method for Detection of Dgug Resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemotherap. 2002; 46 8: 2720–2.

14. Aleksandrova AE, Arijel BM, Ocenka tjazhesti tuberkuleznogo processa v legkih myshej. Problemy tuberkuleza. 1993; 3: 52–53. Russian.

15. Franzblau SG, DeGroote MA, Cho SH, Andries K, Nuermberger E, OrmeI M, et al. Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. Tuberculosis. 2012; 92: 453–88.

16. Metodicheskie ukazanija po izucheniju i ocenke virulicidnoj aktivnosti dezinficirujushhih sredstv. Rukovodstvo. MU 3.5.243108. M., 2010. Russian.

17. Rasimick BJ, Nekich M, Hladek MM, Barry L. Musikant BI, Deutsch AS. Interaction between Chlorhexidine Digluconate and EDTA. JOE. 2008; 34 (12): 1521–3.