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Repurposing licensed, inexpensive non-antibiotic drugs may provide a strategy for enhancing the activity of established antimicrobial agents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical isolates from Sana\u2019a, Yemen, and American Type Culture Collection (ATCC) reference strains were tested in vitro with amlodipine, fluoxetine, and escitalopram, individually and in dual or triple combinations with ciprofloxacin or fluconazole. Antimicrobial activity was evaluated using agar-well diffusion, broth microdilution minimum inhibitory concentration (MIC), minimum bactericidal or fungicidal concentration (MBC\/MFC), and checkerboard fractional inhibitory concentration index (FICI) assays. Molecular docking with AutoDock Vina was used to explore plausible interactions with MurB (PDB 1HSK), LasR (PDB 3IX3), and CYP51 (PDB 5V5Z). Normal mode analysis (NMA) with iMODS was performed for selected fluoxetine\u2013LasR and fluoxetine\u2013MurB complexes as a preliminary structural-dynamics assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fluoxetine produced inhibition zones of at least 27\u00a0mm across the tested organisms. Amlodipine produced larger zones against\n                      <jats:italic>S. aureus<\/jats:italic>\n                      and\n                      <jats:italic>C. albicans<\/jats:italic>\n                      than against\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , whereas escitalopram produced smaller zones overall. Checkerboard testing identified synergy (FICI\u2009\u2264\u20090.50) for selected combinations. Selected triple combinations reduced MIC values by 4- to 64-fold. The largest diffusion readouts were observed with ciprofloxacin\u2009+\u2009fluoxetine\u2009+\u2009amlodipine against\n                      <jats:italic>S. aureus<\/jats:italic>\n                      (101\u00a0mm), ciprofloxacin\u2009+\u2009fluoxetine\u2009+\u2009escitalopram against\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      (88.5\u00a0mm), and ciprofloxacin\u2009+\u2009amlodipine\u2009+\u2009fluconazole against\n                      <jats:italic>C. albicans<\/jats:italic>\n                      (138.5\u00a0mm). Docking scores and NMA outputs provided hypothesis-generating structural context for the experimental findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Antimicrobial enhancement was combination- and organism-dependent. Selected combinations showed checkerboard-defined synergy, whereas diffusion assays were interpreted as screening outcomes only. Docking and NMA findings were supportive and hypothesis-generating but did not establish target engagement or mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-05443-4","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:07:48Z","timestamp":1784772468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing amlodipine, fluoxetine, and escitalopram as non-antibiotic adjuvants: in vitro enhancement of ciprofloxacin and fluconazole activity against multidrug-resistant bacterial and candida clinical isolates"],"prefix":"10.1186","volume":"26","author":[{"given":"Mohammed A.","family":"Alkhawlani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa M.","family":"Al-Madhagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Mahyoob","family":"Alburyhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Gamal","family":"Al-kaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Al-Najar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"5443_CR1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","volume":"399","author":"CJL Murray","year":"2022","unstructured":"Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. 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The requirement for informed consent to participate was waived by the Al-Nasser University Research Ethics Committee (Approval No. NU-RECM23018), because this study used only de-identified, leftover clinical isolates with no access to patient-identifiable information. All procedures were performed in accordance with relevant institutional and national guidelines and with the principles of the Declaration of Helsinki as applicable to research using de-identified, human-derived materials.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This manuscript does not contain any individual person\u2019s data in any form (including individual details, images, or videos).","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"901"}}