{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:55:13Z","timestamp":1790283313120,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/AuthorWarrantyLicense.v1"},{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            -associated infective endocarditis represents difficult-to-treat, deep-seated infections. Phage-antibiotic combinations have shown to eradicate multi-drug resistant (MDR)\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            , limit the development of phage resistance, and restore antibiotic sensitivity. The objective of this study was to evaluate the activity of phage-ciprofloxacin (CIP) combinations in 4-day\n            <jats:italic>ex vivo<\/jats:italic>\n            simulated endocardial vegetation (SEV) models against drug-resistant\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            isolates. Two\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            isolates, extensively drug-resistant AR351 and MDR I0003-1, were selected for their drug resistance and sensitivity to phage. Three phages [LL-5504721-AH (LL), E2005-C (EC), and 109] and CIP were evaluated alone and in combination for their activity and influence on drug and phage resistance using 24-h time-kill analysis. The three-phage cocktail (q24h) in combination with CIP (400 mg q12h) was then tested in dynamic 4-day\n            <jats:italic>ex vivo<\/jats:italic>\n            SEV models, with reduction of log\n            <jats:sub>10<\/jats:sub>\n            CFU\/mL compared using ANOVA with Bonferroni analysis. Compared to other combinations, CIP-LL-EC-109 demonstrated synergistic and bactericidal activity from starting CFU\/g against AR351 and I0003-1 (\u2212\u03945.65 and 6.60 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g, respectively;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). Additionally, CIP-LL-EC-109 mitigated phage resistance, while all other therapies had a high degree of resistance to &gt;1 phages, and all phage-containing regimens prevented CIP mean inhibitory concentration increases compared to CIP alone for both AR351 and I0003-1 at 96 h.\n          <\/jats:p>","DOI":"10.1128\/aac.00728-23","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T13:01:23Z","timestamp":1698238883000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Ciprofloxacin in combination with bacteriophage cocktails against multi-drug resistant\n            <i>Pseudomonas aeruginosa<\/i>\n            in\n            <i>ex vivo<\/i>\n            simulated endocardial vegetation models"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-0048","authenticated-orcid":true,"given":"Amer","family":"El Ghali","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Stamper","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-8625","authenticated-orcid":false,"given":"Ashlan J.","family":"Kunz Coyne","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-7015","authenticated-orcid":false,"given":"Dana","family":"Holger","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Kebriaei","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Virology and Immunology, AdventHealth Central Florida , Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8148","authenticated-orcid":false,"given":"Susan M.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0081","authenticated-orcid":true,"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences , Detroit, Michigan, USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Wayne State University , Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Centers for Disease Control and Prevention (U.S.)\n. 2019. 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