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Biofilm formation further complicates therapeutic strategies. This study investigated the synergistic effects of combining norfloxacin (NOR) and sulfadiazine (SDZ) against three Escherichia coli strains: a reference, a quinolone-resistant clinical isolate, and a highly resistant extended-spectrum \u03b2-lactamase (ESBL)-producing strain. Checkerboard assays and isobolograms revealed synergistic or partially synergistic effects across all strains, with Fractional Inhibitory Concentration Index (FICI) values ranging from 0.37 to 1.0. Notably, the ESBL strain displayed enhanced synergy (FICI\u00a0=\u00a00.75) under white LED light irradiation. Reactive oxygen species (ROS) analysis showed that SDZ generated higher levels than NOR, particularly in the quinolone-resistant clinical isolate, while the NOR\u2013SDZ combination yielded lower levels. Scanning electron microscopy of biofilms confirmed that the drug combination caused greater structural disruption than either monotherapy, especially at NOR (FIC\u00a0\u00d7\u00a0100) and SDZ (FIC\u00a0\u00d7\u00a010). Subinhibitory monotherapies modulated the biofilm phenotype, underscoring the benefits of combined treatments. Overall, these findings highlight the NOR\u2013SDZ combination as a promising therapeutic approach against MDR E. coli, where drug synergy and biofilm disruption emerge as key strategies to combat antimicrobial resistance.<\/jats:p>","DOI":"10.1093\/femsle\/fnag054","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:35:29Z","timestamp":1777563329000},"source":"Crossref","is-referenced-by-count":0,"title":["Synergistic antibacterial activity of norfloxacin and sulfadiazine against planktonic and biofilm-forming multidrug-resistant\n                    <i>Escherichia coli<\/i>\n                    strain"],"prefix":"10.1093","volume":"373","author":[{"given":"Rosal\u00eda Ayala","family":"G\u00f3mez","sequence":"first","affiliation":[{"name":"Universidad Nacional de la Patagonia San Juan Bosco Departamento de Farmacia, Centro Regional de Investigaci\u00f3n y Desarrollo Cient\u00edfico Tecnol\u00f3gico (CRIDECIT), , Comodoro Rivadavia 9000 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