{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:24:08Z","timestamp":1782894248406,"version":"3.54.5"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cG. D\u2019ANNUNZIO\u201d UNIVERSITY OF CHIETI-PESCARA","award":["FAR \u201cex-60%\u201d"],"award-info":[{"award-number":["FAR \u201cex-60%\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antibiotic therapy faces challenges from rising acquired and biofilm-related antibiotic resistance rates. High resistance levels to commonly used antibiotics have been observed in methicillin-resistant Staphylococcus\u00a0aureus (MRSA) strains among cystic fibrosis (CF) patients, indicating an urgent need for new antibacterial agents. This study aimed to identify potential novel therapeutics with antibacterial and antibiofilm activities against an MRSA CF strain by screening, for the first time, the Drug Repurposing Compound Library (MedChem Express). Methods\/Results: Among the 3386 compounds, a high-throughput screening-based spectrophotometric approach identified 2439 (72%), 654 (19.3%), and 426 (12.6%) drugs active against planktonic cells, biofilm formation, and preformed biofilm, respectively, although to different extents. The most active hits were 193 (5.7%), against planktonic cells, causing a 100% growth inhibition; 5 (0.14%), with excellent activity against biofilm formation (i.e., reduction \u2265 90%); and 4, showing high activity (i.e., 60% \u2264 biofilm reduction &lt; 90%) against preformed biofilms. The potential hits belonged to several primary research areas, with \u201ccancer\u201d being the most prevalent. After performing a literature review to identify other, already published biological properties that could be relevant to the CF lung environment (i.e., activity against other CF pathogens, and anti-inflammatory and anti-virulence potential), the most interesting hits were the following: 5-(N,N-Hexamethylene)-amiloride (diuretic), Toremifene (anticancer), Zafirlukast (antiasthmatic), Fenretide (anticancer), and Montelukast (antiasthmatic) against planktonic S. aureus cells; Hemin against biofilm formation; and Heparin, Clemastine (antihistaminic), and Bromfenac (nonsteroidal anti-inflammatory) against established biofilms. Conclusions: These findings warrant further in vitro and in vivo studies to confirm the potential of repurposing these compounds for managing lung infections caused by S. aureus in CF patients.<\/jats:p>","DOI":"10.3390\/antibiotics14040402","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:18:36Z","timestamp":1744611516000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-Resistant Staphylococcus aureus from a Cystic Fibrosis Patient"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6309-6981","authenticated-orcid":false,"given":"Arianna","family":"Pompilio","sequence":"first","affiliation":[{"name":"Department of Medical, Oral and Biomedical Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lupetti","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biomedical Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-876X","authenticated-orcid":false,"given":"Valentina","family":"Puca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5850-2810","authenticated-orcid":false,"given":"Giovanni","family":"Di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biomedical Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1039\/C9MD00044E","article-title":"Methicillin-resistant Staphylococcus aureus (MRSA): Antibiotic-resistance and the biofilm phenotype","volume":"10","author":"Craft","year":"2019","journal-title":"MedChemComm"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1164\/rccm.200802-327OC","article-title":"Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis","volume":"178","author":"Dasenbrook","year":"2008","journal-title":"Am. 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