{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:13:31Z","timestamp":1779329611850,"version":"3.51.4"},"reference-count":9,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["EXC 2167-390884018"],"award-info":[{"award-number":["EXC 2167-390884018"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["TTU 08.824"],"award-info":[{"award-number":["TTU 08.824"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Antimicrobial resistance development, particularly in infections such as urinary tract infections (UTIs), is a global clinical concern. The objective of this study was to determine if sequential antibiotic exposure with ciprofloxacin and mecillinam can reduce the growth of resistant clinical\n              <jats:italic>Escherichia coli<\/jats:italic>\n              strains, thus improving the effectiveness of antibiotic therapy. Six\n              <jats:italic>E. coli<\/jats:italic>\n              isolates with heterogeneous resistance to ciprofloxacin and\/or mecillinam obtained from patients with UTIs were exposed to one of the antibiotics (0.75 \u00d7 minimum inhibitory concentration, MIC) for 1 h. This was followed by treatment with the second antibiotic at different concentrations (0.0375\/0.075\/0.375\/0.75 \u00d7 MIC). Continuous growth measurements were conducted in order to assess the impact of sequential exposure. One representative strain was selected for intact cell counting. In addition, a checkerboard assay was conducted to investigate the synergistic impact of ciprofloxacin and mecillinam, and genetic analyses were performed to identify the mechanisms of resistance for all isolates. The six\n              <jats:italic>E. coli<\/jats:italic>\n              strains were phylogenetically different, and none exhibited a synergistic effect for ciprofloxacin and mecillinam. Our data suggest that sequential exposure to mecillinam and ciprofloxacin appears to reduce the growth capacity of clinical\n              <jats:italic>E. coli<\/jats:italic>\n              isolates with phenotypic resistance to either or both agents. Sequential antibiotic exposure may be an interesting strategy to improve the antibiotic efficacy of current agents to overcome phenotypic resistance in\n              <jats:italic>E. coli<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              As global rates of antibiotic resistance increase and the development of new antibiotics become more difficult and costly, it is important to explore alternative strategies to improve the effectiveness of existing antibiotics. Previous studies have shown that sequential exposure of\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              to two antibiotics can effectively kill the bacteria and reduce the likelihood of resistance developing. However, the potential of this sequential approach for the treatment of\n              <jats:italic>Escherichia coli<\/jats:italic>\n              infections has not been thoroughly investigated. In our study, we conducted a proof-of-principle study to determine whether sequential exposure to mecillinam and ciprofloxacin can overcome phenotypic resistance to one or both drugs. We found that when\n              <jats:italic>E. coli<\/jats:italic>\n              were treated with subinhibitory doses of mecillinam followed by ciprofloxacin, their growth was significantly inhibited compared to treatment with ciprofloxacin alone, suggesting that sequential antibiotic exposure may be a viable strategy for treating infections caused by resistant\n              <jats:italic>E. coli<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02525-24","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T14:00:43Z","timestamp":1738677643000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the effect of sequential antibiotic exposure in resistant\n            <i>Escherichia coli<\/i>\n            causing urinary tract infections: a proof of principle study"],"prefix":"10.1128","volume":"13","author":[{"given":"Lisa","family":"G\u00f6pel","sequence":"first","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Kirchhoff","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Gopleac","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif","family":"T\u00fceffers","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Hauswaldt","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Boutin","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]},{"name":"German Center for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems","place":["L\u00fcbeck, Germany"]},{"name":"Airway Research Center North (ARCN), German Center for Lung Research (DZL)","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-1233","authenticated-orcid":true,"given":"Jan","family":"Rupp","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]},{"name":"German Center for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-5939","authenticated-orcid":true,"given":"Dennis","family":"Nurjadi","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck and University Hospital Schleswig-Holstein Campus L\u00fcbeck, Institute of Medical Microbiology and Infectious Diseases Clinic","place":["L\u00fcbeck, Germany"]},{"name":"German Center for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems","place":["L\u00fcbeck, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3432"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4103\/jgid.jgid_104_17"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810004115"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409800111"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68876"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006609"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009940"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06143-y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00902-5"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02525-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02525-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T14:07:07Z","timestamp":1741097227000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02525-24"}},"subtitle":[],"editor":[{"given":"Aude A.","family":"Ferran","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":9,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,4]]}},"alternative-id":["10.1128\/spectrum.02525-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02525-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"2024-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02525-24"}}