INTRODUCTION: Skin infections due to bacteria represent significant morbidity and mortality in healthcare. Staphylococcus aureus (SA) is of particular importance because it is the most commonly isolated pathogen in surgical site infections, diabetic foot ulcers, and chronic wounds.1 The current treatment for skin infections ranges from empiric antibiotic therapy to aggressive surgical debridement. Mild hyperthermia, defined as temperatures less than 42°C, has been show to enhance antimicrobial activity and represents a new approach for the treatment of local infections.2, 3 The aim of this study was to investigate whether novel polymer nanoparticles, capable of producing localized mild hyperthermia when exposed to infrared light, can be used to more effectively treat infectious skin lesions while sparing the surrounding healthy tissue.
AIM: Evaluate the efficacy of nanoparticle-mediated mild hyperthermia to augment localized antibiotic activity and reduce bacterial colonization in an infectious skin lesion mouse model.
METHODS: Sixteen Balb/C mice received subcutaneous injections of live bioluminescent SA to develop the skin lesions. After three days, the mice were randomly sorted to receive standardized concentrations of intralesional gentamicin, intralesional nanoparticles, and/or localized infrared laser therapy. Twenty-four hours after treatment, the animals were imaged with the in vivo imaging system (IVIS) to detect SA bioluminescence and nanoparticle fluorescence within the lesions. Each lesion was analyzed using region-of-interest photon emission from the SA colonies.
RESULTS: Bacterial bioluminescence was detected using IVIS and allowed for the identification of bacteria within and outside the visible lesion. Nanoparticle fluorescence was also detected and demonstrated successful co-localization with bacteria in the skin lesions. Treatment with nanoparticles, gentamicin, and infrared light resulted in a 92% reduced detection of bacterial colonies compared to treatment with gentamicin alone.
CONCLUSION: This project establishes an innovative animal model to investigate the use of mild heat-generating nanoparticles as a novel treatment for infectious lesions. Treatment with nanoparticles, gentamicin, and infrared light was the most successful at limiting bacterial proliferation as detected by luminescence signal. Now that a preclinical animal model utilizing bioluminescent bacteria and fluorescent nanoparticles has been established, this study can be expanded to include larger sample sizes, as well as to explore the effects of localized mild hyperthermia on antimicrobial activity, long-term wound healing, aesthetics, and pathogen eradication. In addition, the successful use of bioluminescent bacteria for in vitro colony identification and differentiation can be expanded to other non-sterile infectious models and those with a risk of sample contamination.
1. Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clinical Microbiology Reviews. 2015;28(3):603–661. doi:10.1128/CMR.00134-14.
2. Ricker EB, Nuxoll E. Synergistic effects of heat and antibiotics on Pseudomonas aeruginosa biofilms. Biofouling: The Journal of Bioadhesion and Biofilm Research. 2017;33(10):855–866. doi:10.1080/08927014.2017.1381688.
3. Richardson IP, Sturtevant R, Heung M, Solomon MJ, Younger JG, VanEpps JS. Hemodialysis Catheter Heat Transfer for Biofilm Prevention and Treatment. ASAIO journal (American Society for Artificial Internal Organs: 1992). 2016;62(1):92–99. doi:10.1097/MAT.0000000000000300.