Abstract
Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin’s in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (107 CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log10 reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log10 reduction) and oral clindamycin (1.24-log10 reduction), which are used to treat infected PUs clinically. The present study highlights auranofin’s potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.
Highlights
Pressure ulcers (PUs), commonly referred to as pressure sores or decubitus ulcers, are defined as “localized injury to the skin and/or underlying tissue” that often form when skin is compressed between bone and an external surface[1]
The formation of biofilms within PUs that protect the pathogen from the effect of many antibiotics, secretion of toxins by the pathogen that lead to further damage of the skin and surrounding tissues, and the emergence of multidrug-resistant strains, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), have compounded treatment of infected PUs4
We determined that auranofin exhibited potent in vitro antibacterial activity against strains of methicillin-sensitive S. aureus, MRSA, and VRSA with minimum inhibitory concentration (MIC) values ranging from 0.015 –0.06 μg/mL (Table 1)
Summary
Pressure ulcers (PUs), commonly referred to as pressure sores or decubitus ulcers, are defined as “localized injury to the skin and/or underlying tissue” that often form when skin is compressed between bone and an external surface[1]. Bacterial infection of PUs is common and problematic as infection can (1) impair healing of the ulcerated tissue, (2) lead to more serious disseminated infections including osteomyelitis and sepsis, and (3) result in increased treatment costs[4,5,6]. Staphylococcus aureus and Gram-negative bacilli are the most frequent bacterial pathogens linked to infected PUs4,7. Such infections can be treated with systemic (such as clindamycin) or topical antibiotics (such as mupirocin or fusidic acid)[7,8]. The formation of biofilms within PUs that protect the pathogen from the effect of many antibiotics, secretion of toxins by the pathogen that lead to further damage of the skin and surrounding tissues, and the emergence of multidrug-resistant strains, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), have compounded treatment of infected PUs4. As infected PUs are a notable challenge to obese individuals, the main objective of the present study was to investigate auranofin’s ability to reduce the burden of MRSA in infected PUs in obese mice
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