Protocatechuic Acid as a Topical Antimicrobial for Surgical Skin Antisepsis

Abstract

Background: There is a need for novel skin antiseptic agents to combat the health-care burdens associated with surgical site infection (SSI) and bacterial resistance. The purpose of this proof-of-principle pilot study was to investigate the potential of the phenolic compound protocatechuic acid (PCA) as a topical antimicrobial for surgical skin antisepsis. Methods: The Kirby-Bauer method of disc diffusion was used to investigate the in vitro antimicrobial activity and comparative effectiveness of PCA and 7 related compounds against SSI pathogens. To explore the in vivo efficacy of topical PCA for providing deep, penetrating skin antisepsis, living Cutibacterium acnes was intradermally injected into the skin of female BALB/c mice. Mice were assigned to treatment with daily applications of topical PCA at 3 doses (78, 39, and 19.5 mM) or no treatment (n = 2 mice per group). After 96 hours, infected skin samples were harvested to compare mean C. acnes counts by treatment. Results: Compared with other polyphenols, PCA demonstrated the broadest spectrum of antimicrobial activity against tested SSI pathogens, including drug-resistant organisms. At 96 hours following infection, the mean C. acnes burden in untreated mice was 6.65 log colony-forming units (CFUs) per gram of skin. Compared with the untreated group, daily topical application of 78 mM of PCA was associated with a significantly lower C. acnes CFU burden in mice skin (mean, 5.51 log CFUs per gram of skin; p = 0.0295). Both lower dosages of topical PCA failed to show an effect. Conclusions: PCA demonstrated laboratory efficacy against pathogens implicated in SSI, including drug-resistant organisms. In vivo, topical PCA demonstrated dose-dependent skin penetration and antimicrobial activity against mouse skin C. acnes loads. Human clinical studies exploring the antimicrobial efficacy of topical PCA for preoperative shoulder skin antisepsis are warranted. Clinical Relevance: Topical PCA may have the potential to improve current shoulder SSI treatment and prevention protocols.

Reduced Bacterial Burden of the Skin Surrounding the Shoulder Joint Following Topical Protocatechuic Acid Application

“…The daily application of 78 mM topical PCA resulted in an approximately 13.8-times lower C. acnes load in harvested skin specimens compared with untreated mice. However, both lower doses (39 and 19.5 mM) failed to show an effect 12 . In agreement with the findings of Zillich et al, these experiments suggested that the skin penetrative properties of topical PCA were dose-dependent and that increasing doses could improve the antimicrobial activity of topical PCA against dermal C. acnes loads in living skin.…”

“…In other work by our group, we performed antimicrobial susceptibility testing of PCA and 7 related phenolic compounds against several common pathogens. Compared with related compounds, PCA demonstrated the broadest spectrum of antimicrobial activity, including efficacy against organisms including S. aureus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, and C. acnes, among others 12 . These findings suggest that PCA was the likely active antimicrobial component seen in prior food-plant-based studies, and help to identify its potential for clinical application in the treatment of skin and wound pathogens.…”

“…Natural substrates with antimicrobial properties have been identified as potential sources of novel antimicrobials 11 . In preclinical work by our group, we demonstrated the broad-spectrum, in vitro antimicrobial efficacy of protocatechuic acid (PCA), a phytochemical found in food plants 12 . PCA demonstrated laboratory efficacy against skin and wound pathogens and known drug-resistant organisms 12 .…”

“…In preclinical work by our group, we demonstrated the broad-spectrum, in vitro antimicrobial efficacy of protocatechuic acid (PCA), a phytochemical found in food plants 12 . PCA demonstrated laboratory efficacy against skin and wound pathogens and known drug-resistant organisms 12 . Daily application of topical PCA was then shown to result in a dose-dependent reduction in dermal C. acnes loads in a mouse model of dermal skin infection 12 .…”

“…PCA demonstrated laboratory efficacy against skin and wound pathogens and known drug-resistant organisms 12 . Daily application of topical PCA was then shown to result in a dose-dependent reduction in dermal C. acnes loads in a mouse model of dermal skin infection 12 .…”