Human Trial for the Effect of Plasma-Activated Water Spray on Vaginal Cleaning in Patients with Bacterial Vaginosis

Yongwoo Jang, Junsoo Bok, Dong Keun Ahn, Chang-Koo Kim, Ju-Seop Kang, Yongwoo Jang, Junsoo Bok, Dong Keun Ahn, Chang-Koo Kim, Ju-Seop Kang

Abstract

Underwater plasma discharge temporally produces several reactive radicals and/or free chlorine molecules in water, which is responsible for antimicrobial activity. Hence, it can simply sanitize tap water without disinfectant treatment. Additionally, the spraying technique using cleaning water exploits deep application in the narrow and curved vaginal tract of patients. Herein, we attempted a clinical trial to evaluate the vaginal cleaning effect of spraying plasma-activated water (PAW) to patients with vaginitis (46 patients). The efficacy was compared with treatment with betadine antiseptics used to treat bacterial vaginosis (40 patients). To evaluate the cleaning effect, Gram staining of the vaginal secretions was conducted before and after spraying PAW or betadine treatment (BT). Consequently, PAW-sprayed (PAWS) patients (22.3%) showed a better vaginal cleaning effect against Gram-positive and -negative bacteria than BT patients (14.4%). Moreover, 18 patients in the BT group showed worsened vaginal contamination, whereas five patients in the PAWS group showed worsened vaginal contamination. Taken together, the noncontact method of spraying cleaning water to the vagina exhibited a reliable vaginal cleaning effect without further bacterial infection compared with BT. Therefore, we suggest a clinical application of the spraying method using PAW for vaginal cleaning to patients with vaginitis without disinfectants and antibiotics.

Keywords: bacterial vaginosis; plasma-activated water; underwater plasma discharge; vaginal cleaning.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Beeswarm boxplot of the percentage of reduced bacteria, including Gram-positive cocci (A), Gram₋positive bacilli (B), Gram₋positive coccobacilli (C), Gram₋negative bacilli (D), and Gram₋negative coccobacilli (E), in betadine treatment (BT, blue) and plasma₋activated water sprayed (PAWS, red) patients. (F) Beeswarm boxplot of the number of overgrowth cases after the application of BT or PAWS. All the results are expressed as means ± standard deviation (SD).

References

    1. Russo R., Karadja E., De Seta F. Evidence-based mixture containing Lactobacillus strains and lactoferrin to prevent recurrent bacterial vaginosis: A double blind, placebo controlled, randomised clinical trial. Benef. Microbes. 2019;10:19–26. doi: 10.3920/BM2018.0075.
    1. Verhelst R., Verstraelen H., Claeys G., Verschraegen G., Delanghe J., Van Simaey L., De Ganck C., Temmerman M., Vaneechoutte M. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol. 2004;4:16. doi: 10.1186/1471-2180-4-16.
    1. Castro J., Machado D., Cerca N. Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: The impact of other vaginal pathogens living as neighbors. ISME J. 2019;13:1306–1317. doi: 10.1038/s41396-018-0337-0.
    1. Swidsinski A., Mendling W., Loening-Baucke V., Ladhoff A., Swidsinski S., Hale L.P., Lochs H. Adherent biofilms in bacterial vaginosis. Obstet. Gynecol. 2005;106:1013–1023. doi: 10.1097/01.AOG.0000183594.45524.d2.
    1. Verstraelen H., Swidsinski A. The biofilm in bacterial vaginosis: Implications for epidemiology, diagnosis and treatment: 2018 update. Curr. Opin. Infect. Dis. 2019;32:38–42. doi: 10.1097/QCO.0000000000000516.
    1. Rosca A.S., Castro J., Franca A., Vaneechoutte M., Cerca N. Gardnerella Vaginalis Dominates Multi-Species Biofilms in both Pre-Conditioned and Competitive In Vitro Biofilm Formation Models. Microb. Ecol. 2021 doi: 10.1007/s00248-021-01917-2. in press .
    1. Machado A., Cerca N. Influence of Biofilm Formation by Gardnerella vaginalis and Other Anaerobes on Bacterial Vaginosis. J. Infect. Dis. 2015;212:1856–1861. doi: 10.1093/infdis/jiv338.
    1. Gilbert N.M., Lewis W.G., Lewis A.L. Clinical features of bacterial vaginosis in a murine model of vaginal infection with Gardnerella vaginalis. PLoS ONE. 2013;8:e59539. doi: 10.1371/journal.pone.0059539.
    1. Campoccia D., Montanaro L., Arciola C.R. Extracellular DNA (eDNA). A Major Ubiquitous Element of the Bacterial Biofilm Architecture. Int. J. Mol. Sci. 2021;22:9100. doi: 10.3390/ijms22169100.
    1. Hoiby N., Ciofu O., Johansen H.K., Song Z.J., Moser C., Jensen P.O., Molin S., Givskov M., Tolker-Nielsen T., Bjarnsholt T. The clinical impact of bacterial biofilms. Int. J. Oral. Sci. 2011;3:55–65. doi: 10.4248/IJOS11026.
    1. Machado D., Castro J., Palmeira-de-Oliveira A., Martinez-de-Oliveira J., Cerca N. Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions. Front. Microbiol. 2015;6:1528. doi: 10.3389/fmicb.2015.01528.
    1. Zhao Y.M., Ojha S., Burgess C.M., Sun D.W., Tiwari B.K. Inactivation efficacy and mechanisms of plasma activated water on bacteria in planktonic state. J. Appl. Microbiol. 2020;129:1248–1260. doi: 10.1111/jam.14677.
    1. Zhou R.W., Zhou R.S., Prasad K., Fang Z., Speight R., Bazaka K., Ostrikov K. Cold atmospheric plasma activated water as a prospective disinfectant: The crucial role of peroxynitrite. Green Chem. 2018;20:5276–5284. doi: 10.1039/C8GC02800A.
    1. Mai-Prochnow A., Zhou R., Zhang T., Ostrikov K.K., Mugunthan S., Rice S.A., Cullen P.J. Interactions of plasma-activated water with biofilms: Inactivation, dispersal effects and mechanisms of action. NPJ Biofilm. Microbiomes. 2021;7:11. doi: 10.1038/s41522-020-00180-6.
    1. Tan J., Karwe M.V. Inactivation and removal of Enterobacter aerogenes biofilm in a model piping system using plasma-activated water (PAW) Innov. Food Sci. Emerg. Technol. 2021;69:102664. doi: 10.1016/j.ifset.2021.102664.
    1. Zhou R., Zhou R., Wang P., Luan B., Zhang X., Fang Z., Xian Y., Lu X., Ostrikov K.K., Bazaka K. Microplasma Bubbles: Reactive Vehicles for Biofilm Dispersal. ACS Appl. Mater. Interfaces. 2019;11:20660–20669. doi: 10.1021/acsami.9b03961.
    1. Chen T.-P., Su T.-L., Liang J. Plasma-activated solutions for bacteria and biofilm inactivation. Curr. Bioact. Compd. 2017;13:59–65. doi: 10.2174/1573407212666160609082945.
    1. Khlyustova A., Labay C., Machala Z., Ginebra M.P., Canal C. Important parameters in plasma jets for the production of RONS in liquids for plasma medicine: A brief review. Front. Chem. Sci. Eng. 2019;13:238–252. doi: 10.1007/s11705-019-1801-8.
    1. Privat-Maldonado A., Schmidt A., Lin A., Weltmann K.D., Wende K., Bogaerts A., Bekeschus S. ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy. Oxidative Med. Cell. Longev. 2019;2019:9062098. doi: 10.1155/2019/9062098.
    1. Lee Y., Ricky S., Lim T.H., Kim H., Lee E.J., Song Y., Lee S., Jang Y. An atmospheric plasma jet induces expression of wound healing genes in progressive burn wounds in a comb burn rat model: A pilot study. J. Burn Care Res. 2021 doi: 10.1093/jbcr/irab005. in press .
    1. Nicol M.J., Brubaker T.R., Honish B.J., 2nd, Simmons A.N., Kazemi A., Geissel M.A., Whalen C.T., Siedlecki C.A., Bilen S.G., Knecht S.D., et al. Antibacterial effects of low-temperature plasma generated by atmospheric-pressure plasma jet are mediated by reactive oxygen species. Sci. Rep. 2020;10:3066. doi: 10.1038/s41598-020-59652-6.
    1. Girard-Sahun F., Badets V., Lefrancois P., Sojic N., Clement F., Arbault S. Reactive Oxygen Species Generated by Cold Atmospheric Plasmas in Aqueous Solution: Successful Electrochemical Monitoring in Situ under a High Voltage System. Anal. Chem. 2019;91:8002–8007. doi: 10.1021/acs.analchem.9b01912.
    1. Lee S., Choi J., Kim J., Jang Y., Lim T.H. Atmospheric Pressure Plasma Irradiation Facilitates Transdermal Permeability of Aniline Blue on Porcine Skin and the Cellular Permeability of Keratinocytes with the Production of Nitric Oxide. Appl. Sci. 2021;11:2390. doi: 10.3390/app11052390.
    1. Lee S.J., Ma S.H., Hong Y.C., Choi M.C. Effects of pulsed and continuous wave discharges of underwater plasma on Escherichia coli. Sep. Purif. Technol. 2018;193:351–357. doi: 10.1016/j.seppur.2017.10.040.
    1. Hong Y.C., Park H.J., Lee B.J., Kang W.S., Uhm H.S. Plasma formation using a capillary discharge in water and its application to the sterilization of E. coli. Phys. Plasmas. 2010;17:053502. doi: 10.1063/1.3418371.
    1. Hwang Y., Jeon H., Wang G.Y., Kim H.K., Kim J.-H., Ahn D.K., Choi J.S., Jang Y. Design and Medical Effects of a Vaginal Cleaning Device Generating Plasma-Activated Water with Antimicrobial Activity on Bacterial Vaginosis. Plasma. 2020;3:204–213. doi: 10.3390/plasma3040016.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere