Plasma-Activated Saline Promotes Antibiotic Treatment of Systemic Methicillin-Resistant Staphylococcus aureus Infection

Abstract

Systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are life-threatening due to their strong multidrug resistance, especially since the biofilms formed by MRSA are more difficult to inactivate by antibiotics, causing long term recurrence of infection. Plasma-activated saline (PAS), a derived form of cold atmospheric-pressure plasma, can effectively inactivate bacteria and cancer cells and has been applied to sterilization and cancer treatment. Previous studies have demonstrated that the pretreatment of MRSA with PAS could promote the action of antibiotics. Here, the PAS was used as an antibiotic adjuvant to promote the inactivation of MRSA biofilms by rifampicin and vancomycin, and the combined treatment reduced approximately 6.0-log10 MRSA cells in biofilms. The plasma-activated saline and rifampicin synergistically and effectively reduced the systemic infection in the murine model. The histochemical analysis and the blood hematological and biochemical test demonstrated that the combined treatment with plasma-activated saline and rifampicin improved the blood hematological and biochemical parameters of infected mice by reducing the infection. Therefore, PAS based on plasma technology represents a new strategy for the treatment of infectious disease caused by multidrug-resistant bacteria and alleviating antibiotic resistance.

Plasma‐activated liquids for mitigating biofilms on food and food contact surfaces

“…Although it is difficult to conclude which working gas is most effective in PALs inactivation of biofilms, many studies have demonstrated that the addition of small amounts of oxygen to noble gases could enhance the antimicrobial activity of PALs, and when the ambient air is used as working gas, greater inactivation efficacy can usually be achieved as compared to noble gases (Li et al, 2015). Yang et al (2021) used synthetic air (79% N 2 + 21% O 2 )-produced plasma-activated saline (PAL) for the inactivation of methicillin-resistant S. aureus (MRSA) biofilms formed on silica films. The treatment of PALs alone achieved an approximately 1.2-log reduction of MRSA cells in the biofilm.…”

“…In recent studies, differences in inactivation efficiency toward plasma-treated solutions in treating different types/forms of microorganisms have been reported. Many studies have used various solutions to generate PALs to investigate their inactivation efficiency toward biofilm cells, including PBS (Hong et al, 2021;İbiş & Ercan, 2020;Joshi et al, 2010;Kwandou et al, 2018;Seo et al, 2019), saline solution (0.9%) (Bhatt et al, 2018;Chen et al, 2016;Hong et al, 2021;Yang et al, 2021), NAC (İbiş & Ercan, 2020), citrate solution (Chen et al, 2016), and a number of organic solutions, including glucose, cysteine, glycine, proline, methionine, threonine, glutamate, arginine, and heparin (Ercan et al, 2014). In the study of Ercan et al (2014), it was reported that the plasma-treated methionine solution was more efficient and significant in inhibiting the biofilms of all the bacterial strains tested (carbapenem-resistant Acinetobacter baumannii, MRSA, metallo-β-lactamase (NDM1)-positive Klebsiella pneumoniae, and Enterococcus faecalis) by preventing the formation of biofilms by 70% as compared to untreated ones.…”

“…3.2-and 3.9-log CFU/mL reduction for biofilms. (Flynn et al, 2016), L. mesenteroides (Kamgang-Youbi et al, 2009), L. monocytogenes, MRSA (Bhatt et al, 2018;Ercan et al, 2014;Kelar Tučeková et al, 2021;Yang et al, 2021), S. epidermidis (Bhatt et al, 2018;Kamgang-Youbi et al, 2009;Kelar Tučeková et al, 2021), S. aureus (Chen et al, 2016), Streptococcus mutans (Hong et al, 2021), S. Typhimurium (Smet et al, 2019;Sysolyatina et al, 2020), P. aeruginosa (Bhatt et al, 2018;Handorf et al, 2020;Kelar Tučeková et al, 2021), Pseudomonas syringae pv. tomato DC3000 (Seo et al, 2019), carbapenem-resistant Acinetobacter baumannii (Ercan et al, 2014), metallo-βlactamase (NDM1)-positive K. pneumonia (Ercan et al, 2014), E. coli (Charoux et al, 2020;Flynn et al, 2016;Kelar Tučeková et al, 2021;Sysolyatina et al, 2020), and fungal biofilms S. cerevisiae (Kamgang-Youbi et al, 2009), E. faecalis (Ercan et al, 2014;Li et al, 2019;Pan et al, 2017), and C. albicans (Bhatt et al, 2018).…”

“…However, recent studies have demonstrated potential applications of combined treatments for PALs with other technologies for the inactivation of biofilms. In the study conducted by Yang et al (2021), synthetic air (79% N 2 + 21% O 2 )-produced PALs were used as an antibiotic adjuvant in the combined treatment with antibiotics (rifampicin and vancomycin) to promote the inactivation of MRSA biofilms formed on silica films. The treatment of PALs alone achieved an approx-imately 1.2-log reduction of MRSA cells in the biofilm, while the combined treatment of PALs and antibiotics (vancomycin or rifampicin) reduced ∼≥6log reduction of MRSA cells in the biofilms.…”

Applications of Plasma-Activated Liquid in the Medical Field

“…In medicine, plasma has received a lot of attention as a novel tool, and the field of plasma medicine was created, and PAL is also being discussed as an aqueous plasma pharmacy as a field within plasma medicine [16,39]. In the area of PAL, in addition to the wound healing, disinfection, and cancer therapy mentioned above, active research is being conducted on making plasmaactivated oil or hydrogel [116,117], combined therapy with other treatments [123], and interaction with drugs [124].…”