{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:09:55Z","timestamp":1791846595612,"version":"4.3.4"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The aim of this study is to evaluate the pH-dependent antimicrobial activities of delafloxacin against isogenic\n Escherichia coli<\/jats:italic>\n strains carrying diverse fluoroquinolone resistance mechanisms. Eighty-one isogenic\n E. coli<\/jats:italic>\n strains derived from ATCC 25922 were tested, carrying various combinations of chromosomal mutations (\n gyrA, parC<\/jats:italic>\n ), efflux pump overexpression (\n marR<\/jats:italic>\n ), and plasmid-mediated quinolone resistance (PMQR) determinants (\n qnrA1, qnrB1, qnrC, qnrD1, qnrS1, qepA2, aac(6')-Ib-cr<\/jats:italic>\n ). Minimum inhibitory concentrations (MICs) were determined using broth microdilution at pH 7.3, 6.0, and 5.0. Time-killing assays were performed on three representative strains. Semi-mechanism-based mathematical modeling using Monolix quantified bactericidal activity through EC\n 50<\/jats:sub>\n parameters. Ciprofloxacin MIC\n 90<\/jats:sub>\n increased from 8 mg\/L at pH 7.3 to 128 mg\/L at pH 5.0, while delafloxacin MIC\n 90<\/jats:sub>\n decreased from 64 mg\/L to 16 mg\/L. At physiological pH, ciprofloxacin demonstrated superior activity (median MIC: 1 mg\/L vs 8 mg\/L for delafloxacin,\n P<\/jats:italic>\n < 0.001), while at pH 5.0, delafloxacin median MIC was 2 mg\/L versus 64 mg\/L for ciprofloxacin (\n P<\/jats:italic>\n < 0.001). According to EUCAST breakpoints, susceptibility frequencies at pH 5.0 were 25.9% (21\/81) for delafloxacin versus 2.5% (2\/81) for ciprofloxacin (\n P<\/jats:italic>\n < 0.001). Among PMQR,\n qnr<\/jats:italic>\n genes led to 0% delafloxacin susceptibility across all conditions (0\/150 strain-pH combinations), while\n qepA2<\/jats:italic>\n (8\/30 strain-pH combinations, 26.7%) and\n aac(6')-Ib-cr<\/jats:italic>\n (16\/30 strain-pH combinations, 53.3%) showed comparable susceptibility frequencies to isogenic strains not carrying PMQR (15\/33 strain-pH combinations, 45.5%). Simulated clinical exposures against chromosomal mutant EC02 (GyrA-S83L) demonstrated that ciprofloxacin would fail at pH 5.0, while delafloxacin would maintain antimicrobial activity. Environmental pH deeply modulates fluoroquinolone activity and resistance mechanism impact. Delafloxacin demonstrates clinically relevant activity in acidic infection environments.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Fluoroquinolones face increasing resistance challenges, particularly in acidic infection sites, such as the urinary tract, abscesses, and biofilms, where pH can drop below 6.0. This study reveals a critical pH-dependent reversal in antimicrobial effectiveness between ciprofloxacin and delafloxacin against resistant\n Escherichia coli<\/jats:italic>\n . While ciprofloxacin loses substantial activity in acidic conditions (90% of strains showing 16-fold minimum inhibitory concentration increases at pH 5.0), delafloxacin maintains and even enhances its antimicrobial potency, with susceptibility rates increasing from 25.9% to over 50% as pH decreases. Using comprehensive resistance profiling across 81 isogenic strains and pharmacokinetic modeling, we demonstrate that delafloxacin could overcome treatment failures in acidic infection sites where conventional fluoroquinolones fail. These findings could have immediate clinical implications for treating urinary tract infections, abscesses, and biofilm-associated infections, potentially expanding therapeutic options against multidrug-resistant bacteria in previously challenging anatomical sites.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/spectrum.02338-25","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:03:31Z","timestamp":1761829411000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Effect of pH on antimicrobial activity of delafloxacin against\n Escherichia coli<\/i>\n isogenic strains carrying diverse chromosomal and plasmid-mediated fluoroquinolone resistance mechanisms"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-5695","authenticated-orcid":true,"given":"K.","family":"Alexandre","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Univ Rouen Normandie, Universit\u00e9 de Caen Normandie, INSERM, Normandie Univ, DYNAMICURE UMR 1311, CHU Rouen","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Murillo-Torres","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03yxnpp24","id-type":"ROR","asserted-by":"publisher"}],"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla","place":["Sevilla, Spain"]},{"name":"Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla","place":["Sevilla, 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Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-5891","authenticated-orcid":true,"given":"\u00c1lvaro","family":"Pascual","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03yxnpp24","id-type":"ROR","asserted-by":"publisher"}],"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla","place":["Sevilla, Spain"]},{"name":"Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla","place":["Sevilla, Spain"]},{"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}],"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"id":[{"id":"https:\/\/ror.org\/016p83279","id-type":"ROR","asserted-by":"publisher"}],"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital 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