Authors
Kist, M., Wulandari, I. G. A. I., Buell, J. F., Morici, L. A. J., ROY, C. J.
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a common cause of skin and soft tissue infections, and topical agents that combine antimicrobial activity with wound compatibility are needed. C12-alkyl(ethylbenzyl)dimethyl ammonium chloride is a novel C12 quaternary ammonium molecule (hereafter, EQ12) related to benzalkonium chloride but designed to avoid the compositional heterogeneity and varied potency of conventional C8-C18 benzalkonium mixtures. We evaluated whether topical EQ12 is tolerated in healing wounds and whether it reduces MRSA burden in a splinted murine excisional wound infection model. Methods: Female CD1 mice underwent 5-mm full-thickness dorsal excisional wounding, silicone splinting, and transparent dressing placement. For tolerability studies, uninfected wounds received EQ12 at 0.1 or 1 mg/mL or phosphate-buffered saline (PBS) and were followed for 14 days. For efficacy studies, wounds were inoculated with 1 x 104 CFU MRSA and treated topically every 8 hours for 3 days beginning 4 hours after infection with EQ12 (1 mg/mL), bacitracin (500 U/mL), or PBS. Wound tissues were harvested on days 2, 4, and 6 for quantitative culture. Dressing-associated biofilm was evaluated by scanning electron microscopy. Results: EQ12 did not alter body weight, wound inflammation scores, wound area, or percent wound closure compared with PBS in uninfected animals. In infected wounds, day 2 tissue burdens were not significantly different among treatment groups. By day 4, EQ12 significantly reduced MRSA burden compared with PBS, whereas bacitracin did not. By day 6, EQ12-treated animals had significantly lower MRSA burdens than both bacitracin- and PBS-treated controls. Mean tissue burden in the EQ12 group declined from 6.27 log10 CFU/g on day 4 to 5.53 log10 CFU/g on day 6, while bacitracin- and PBS-treated wounds remained persistently colonized. SEM revealed minimal adherent cocci or matrix-like bridging on dressings from EQ12-treated wounds, in contrast to dense microcolonies and biofilm-like structures on bacitracin and PBS dressings. Conclusions: Topical EQ12 was compatible with gross wound healing and reduced MRSA burden in a dressed, splinted murine wound model. These data support continued development of EQ12 as a topical anti-staphylococcal wound-directed antimicrobial.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 20 Jul 2026.
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