Evaluation of ebselen in resolving a methicillin-resistant Staphylococcus aureus infection of pressure ulcers in obese and diabetic mice.

Autor: Mohammad H; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America., Abutaleb NS; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America.; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States of America., Dieterly AM; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America., Lyle LT; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America.; Center for Comparative Translational Research, Purdue University, West Lafayette, IN, United States of America., Seleem MN; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America.; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Feb 22; Vol. 16 (2), pp. e0247508. Date of Electronic Publication: 2021 Feb 22 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0247508
Abstrakt: Pressure ulcers (PUs) are a source of morbidity in individuals with restricted mobility including individuals that are obese or diabetic. Infection of PUs with pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), impairs ulcers from healing. The present study evaluated ebselen as a topical antibacterial to treat MRSA-infected PUs. Against two different S. aureus strains, including MRSA USA300, resistance to ebselen did not emerge after 14 consecutive passages. Resistance to mupirocin emerged after only five passages. Additionally, ebselen was found to exert a modest postantibiotic effect of five hours against two MRSA strains. Ebselen was subsequently evaluated in MRSA-infected PUs in two models using obese and diabetic mice. In obese mice, topical ebselen (89.2% reduction) and oral linezolid (84.5% reduction) similarly reduced the burden of MRSA in infected PUs. However, in diabetic mice, topical ebselen (45.8% reduction in MRSA burden) was less effective. Histopathological evaluation of ulcers in diabetic mice determined that ebselen treatment resulted in fewer bacterial colonies deep within the dermis and that the treatment exhibited evidence of epithelial regeneration. Topical mupirocin was superior to ebselen in reducing MRSA burden in infected PUs both in obese (98.7% reduction) and diabetic (99.3% reduction) mice. Ebselen's antibacterial activity was negatively impacted as the bacterial inoculum was increased from 105 CFU/mL to 107 CFU/mL. These results suggest that a higher dose of ebselen, or a longer course of treatment, may be needed to achieve a similar effect as mupirocin in topically treating MRSA-infected pressure ulcers.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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