{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:21:55Z","timestamp":1792099315977,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections. Methods: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 \u00b0C and 40 \u00b0C in plastic jars over three months. Results: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC \u2265 128 \u03bcg\/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC \u2264 8 \u03bcg\/mL. Conclusion: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081638","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T04:16:55Z","timestamp":1660018615000},"page":"1638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-8532","authenticated-orcid":false,"given":"Hani","family":"Naseef","sequence":"first","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Sahoury","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Farraj","sequence":"additional","affiliation":[{"name":"Master Program in Clinical Laboratory Science, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moammal","family":"Qurt","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-5608","authenticated-orcid":false,"given":"Abdallah D.","family":"Abukhalil","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-6821","authenticated-orcid":false,"given":"Nidal","family":"Jaradat","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus P.O. Box 7, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israr","family":"Sabri","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5323-712X","authenticated-orcid":false,"given":"Abdullah K.","family":"Rabba","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmmoud","family":"Sbeih","sequence":"additional","affiliation":[{"name":"Quality Control Department, Beit-Jala Pharmaceutical Co., Ltd., Bethlehem P.O. Box 58, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Walters, K.A. (2002). 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