{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T03:33:52Z","timestamp":1787456032318,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Antibiotic drug combination therapy is critical for the successful treatment of infections caused by multidrug resistant pathogens. We investigated the efficacy of \u03b2-lactam and \u03b2-lactam\/\u03b2-lactamase inhibitor combinations with other antibiotics, against the hypervirulent, ceftazidime\/avibactam resistant <jats:italic>Pseudomonas aeruginosa<\/jats:italic> Liverpool epidemic strain (LES) B58. Although minimum inhibitory concentrations <jats:italic>in vitro<\/jats:italic> differed by up to eighty-fold between standard and host-mimicking media, combinatorial effects only marginally changed between conditions for some combinations. Effective combinations <jats:italic>in vitro<\/jats:italic> were further tested in a chronic, high-density murine infection model. Colistin and azithromycin demonstrated combinatorial effects with ceftazidime and ceftazidime\/avibactam both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Conversely, while tobramycin and tigecycline exhibited strong synergy <jats:italic>in vitro<\/jats:italic>, this effect was not observed <jats:italic>in vivo<\/jats:italic>. Our approach of using host-mimicking conditions and a sophisticated animal model to evaluate drug synergy against bacterial pathogens represents a promising approach. This methodology may offer insights into the prediction of combination therapy outcomes and the identification of potential treatment failures.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1352339","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T04:39:15Z","timestamp":1715661555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Using host-mimicking conditions and a murine cutaneous abscess model to identify synergistic antibiotic combinations effective against Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"14","author":[{"given":"Nikita","family":"Lyons","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L.","family":"Lamont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pletzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"B38","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1128\/AAC.02102-15","article-title":"Distinctive binding of avibactam to penicillin-binding proteins of Gram-negative and Gram-positive bacteria","volume":"60","author":"Asli","year":"2016","journal-title":"Antimicrob. 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