Comparison of Antibacterial Activity and Wound Healing in a Superficial Abrasion Mouse Model of Staphylococcus aureus Skin Infection Using Photodynamic Therapy Based on Methylene Blue or Mupirocin or Both.

Montserrat Pérez,Bernardino Moreno,Yolanda Gilaberte,Pilar Robres,Antonio Rezusta,Rosa Bolea,Maria T. Verde,Vanesa Pérez-Laguna,Carmen Aspiroz

doi:10.3389/fmed.2021.673408

Abstract

Background: Antibiotic resistance and impaired wound healing are major concerns in S. aureus superficial skin infections, and new therapies are needed. Antimicrobial photodynamic therapy (aPDT) is a new therapeutic approach for infections, but it also improves healing in many wound models.Objective: To compare the antimicrobial activity and the effects on wound healing of aPDT based on Methylene Blue (MB-aPDT) with mupirocin treatment, either alone or in combination, in superficial skin wounds of S. aureus-infected mice. Additionally, to evaluate the clinical, microbiological, and cosmetic effects on wound healing.Materials and Methods: A superficial skin infection model of S. aureus was established in SKH-1 mice. Infected wounds were treated with MB-aPDT, MB-aPDT with a daily topical mupirocin or only with mupirocin. No treatment was carried out in control animals. Daily clinical and microbiological examinations were performed until complete clinical wound healing. Histopathological studies and statistical analysis were performed at the end of the study.Results: MB-aPDT treatment induced the best wound healing compared to mupirocin alone or to mupirocin plus MB-aPDT. Superficial contraction at 24 h and a greater reduction in size at 48 h, quicker detachment of the crust, less scaling, and absence of scars were observed. Histopathological studies correlated with clinical and gross findings. By contrast, mupirocin showed the highest logaritmic reduction of S. aureus.Conclusions: MB-aPDT and mupirocin treatments are effective in a murine superficial skin infection model of S. aureus. One session of MB-aPDT was the best option for clinical wound healing and cosmetic results. The addition of mupirocin to MB-aPDT treatment improved antimicrobial activity; however, it did not enhance wound healing. No synergistic antibacterial effects were detected.

Highlights

Staphylococcus spp. causes 90% of torpid wound healing skin infection [1]
Gross, and histopathological examinations, and determination of the bacterial burden in the wound demonstrated that S. aureus grew within the following 48 h post-inoculation reaching its maximum at this time point, when the bacterial count was ≥ 105 CFU/mL and the natural healing occurred at 10–12 days
Comparing the histological events induced by the different treatments, the thickness of the skin layers was lower with MU, followed by MB-Antimicrobial photodynamic therapy (aPDT) and by the combination than of controls (p = 0.007 for dermal thickness) (Table 5)

Summary

Introduction

Staphylococcus spp. causes 90% of torpid wound healing skin infection [1]. Staphylococcus aureus is present in 60% of the biofilms of chronic wounds [2, 3], in the skin of 90% atopic patients [4] and it causes 75% of primary human pyoderma [5]. S. aureus is ubiquitous in the digestive and nasal mucosa and causes purulent dermatoses [9]; in skin infection model, it mimics human disease [10] with suppurative dermatitis and abscesses [11] in mice SKH-1 [12, 13] In this context, murine infection S. aureus models are recommended for in vivo development of new antimicrobials. A superficial S. aureus infection model, better using abrasion that tape stripping, have difficulties due to self-limiting course and quick resolution in maximum 8 days [20] This model requires high bacterial load to infect the wound bed and social isolation of mice previous acclimation, it has been validated to evaluate topical antimicrobial therapies [21, 22]. Antimicrobial photodynamic therapy (aPDT) is a new therapeutic approach for infections, but it improves healing in many wound models

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Discussion

Conclusion