{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:14:13Z","timestamp":1792120453770,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Hungary","award":["SZTESZAOK-KKASZGYA2023\/5S772"],"award-info":[{"award-number":["SZTESZAOK-KKASZGYA2023\/5S772"]}]},{"name":"University Research Scholarship Programme (EK\u00d6P), Ministry of Culture and Innovation, National Research, Development and Innovation Fund","award":["EK\u00d6P-348-SZTE"],"award-info":[{"award-number":["EK\u00d6P-348-SZTE"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antimicrobial resistance (AMR) is an escalating global threat driven by antibiotic misuse and bacterial adaptation. Efflux pumps are major contributors to multidrug resistance in Escherichia coli, as they expel antibiotics and reduce their intracellular activity. This study examined efflux-mediated resistance in extended-spectrum beta-lactamase (ESBL)-producing E. coli and evaluated the potential of several efflux pump inhibitors (EPIs)\u2014promethazine (PMZ), thioridazine (TZ), carbonyl cyanide m-chlorophenyl hydrazine (CCCP), reserpine (RES), and phenyl-arginine-\u03b2-naphthylamide (PA\u03b2N)\u2014as therapeutic adjuncts. Methods: Antibacterial and anti-biofilm activities of EPIs were tested using broth microdilution, real-time fluorimetry, and crystal violet assays, while ceftriaxone\u2013PMZ interactions were assessed by checkerboard analysis. Results: TZ and CCCP showed strain-specific antibacterial activity, whereas PMZ, RES, and PA\u03b2N did not exert any effect. PMZ, TZ, and especially CCCP effectively inhibited efflux pump function, while RES and PA\u03b2N were less active. Biofilm inhibition varied between strains, with PMZ and TZ producing moderate reductions. We observed a quite weak synergism between ciprofloxacin, ceftriaxone, and PMZ; however, the result was not significant. Conclusions: Overall, the results highlight the central role of efflux pumps in ESBL-producing E. coli and indicate that EPIs can reverse resistance (e.g., PMZ) and exhibit potent anti-biofilm activity and show additive interactions with antibiotics. However, further studies are needed to optimize their safety, pharmacokinetics, and antibiotic pairing for potential clinical use.<\/jats:p>","DOI":"10.3390\/antibiotics15030276","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overcoming Multidrug Resistance by Bacterial Efflux Pump Inhibitors in Clinical Escherichia coli Strains"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-5815","authenticated-orcid":false,"given":"Nikoletta","family":"Szemer\u00e9di","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rta","family":"Nov\u00e9","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0218-3842","authenticated-orcid":false,"given":"Danhui","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-6134","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Orosz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9230-8907","authenticated-orcid":false,"given":"J\u00f3zsef","family":"S\u00f3ki","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8085-0950","authenticated-orcid":false,"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salam, M.A., Al-Amin, M.Y., Salam, M.T., Pawar, J.S., Akhter, N., Rabaan, A.A., and Alqumber, M.A.A. 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