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This study aims to overcome FQ resistance in <jats:italic>A. baumannii<\/jats:italic> via the formulation of polymeric nanoFQs. Herein, 80 <jats:italic>A. baumannii<\/jats:italic> isolates were obtained from diverse clinical sources. All <jats:italic>A. baumannii<\/jats:italic> isolates showed high resistance to most of the investigated antimicrobials, including ciprofloxacin (CIP) and levofloxacin (LEV) (97.5%). FQ resistance-determining regions of the <jats:italic>gyrA<\/jats:italic> and <jats:italic>parC<\/jats:italic> genes were the most predominant resistant mechanism, harbored by 69 (86.3%) and 75 (93.8%) of the isolates, respectively. Additionally, plasmid-mediated quinolone resistance genes <jats:italic>aac<\/jats:italic>(<jats:italic>6<\/jats:italic>\u2032)<jats:italic>-Ib<\/jats:italic> and <jats:italic>qnrS<\/jats:italic> were detected in 61 (76.3%) and 2 (2.5%) of the 80 isolates, respectively. The CIP- and LEV-loaded poly \u03b5-caprolactone (PCL) nanoparticles, F<jats:sub>CIP<\/jats:sub> and F<jats:sub>LEV<\/jats:sub>, respectively, showed a 1.5\u20136- and 6\u201312-fold decrease in the MIC, respectively, against the tested isolates. Interestingly, the time kill assay demonstrated that MICs of F<jats:sub>CIP<\/jats:sub> and F<jats:sub>LEV<\/jats:sub> completely killed <jats:italic>A. baumannii<\/jats:italic> isolates after 5\u20136\u00a0h of treatment. Furthermore, F<jats:sub>CIP<\/jats:sub> and F<jats:sub>LEV<\/jats:sub> were found to be efficient in overcoming the FQ resistance mediated by the efflux pumps in <jats:italic>A. baumannii<\/jats:italic> isolates as revealed by decreasing the MIC four-fold lower than that of free CIP and LEV, respectively. Moreover, F<jats:sub>CIP<\/jats:sub> and F<jats:sub>LEV<\/jats:sub> at 1\/2 and 1\/4 MIC significantly decreased biofilm formation by 47\u201393% and 69\u201391%, respectively. These findings suggest that polymeric nanoparticles can restore the effectiveness of FQs and represent a paradigm shift in the fight against <jats:italic>A. baumannii<\/jats:italic> isolates.<\/jats:p>","DOI":"10.1038\/s41598-024-53441-1","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T11:02:30Z","timestamp":1707303750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ciprofloxacin- and levofloxacin-loaded nanoparticles efficiently suppressed fluoroquinolone resistance and biofilm formation in Acinetobacter baumannii"],"prefix":"10.1038","volume":"14","author":[{"given":"Alaa M.","family":"Aboelenin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"El\u2011Mowafy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha M.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona I.","family":"Shaaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Barwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"53441_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nrmicro.2017.148","volume":"16","author":"CM Harding","year":"2018","unstructured":"Harding, C. 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