{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:59:31Z","timestamp":1792511971821,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)3, a neutral and lipophilic iron(III)\u2013tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)3 exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 \u00b5g\/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)3 shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)3 significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% \u00b1 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)3 as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care.<\/jats:p>","DOI":"10.3390\/antibiotics15030298","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:43Z","timestamp":1773655843000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Iron(III)\u2013Tropolone Complex as a Topical Agent Against Drug-Resistant MRSA Skin Infections"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5174-9327","authenticated-orcid":false,"given":"Nalin","family":"Abeydeera","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6037-2581","authenticated-orcid":false,"given":"Guanyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5817-1564","authenticated-orcid":false,"given":"Khalil","family":"Zarea","sequence":"additional","affiliation":[{"name":"Department of Physical Sciences, Chemistry Division, College of Science, Jazan University, P.O. Box. 114, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishnu D.","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-8237","authenticated-orcid":false,"given":"Bogdan M.","family":"Benin","sequence":"additional","affiliation":[{"name":"Cupron Performance Additives, Inc., Richmond, VA 23231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7794-3838","authenticated-orcid":false,"given":"Kalpani M.","family":"Ratnayake","sequence":"additional","affiliation":[{"name":"Department of Earth Sciences, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-2563","authenticated-orcid":false,"given":"Min-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Shik","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ 07932, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-8226","authenticated-orcid":false,"given":"Songping D.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. 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