{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:45:51Z","timestamp":1783694751529,"version":"3.55.0"},"reference-count":23,"publisher":"Microbiology Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"The aim of this study was to compare the inhibitory effect of antibiotic combinations in vitro<\/jats:italic> with efficacy in Galleria mellonella<\/jats:italic> larvae in vivo<\/jats:italic> to identify efficacious combinations that target Pseudomonas aeruginosa<\/jats:italic>. P. aeruginosa<\/jats:italic> NCTC 13437, a multidrug-resistant strain resistant to \u03b2-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured in vitro<\/jats:italic> via a 24 h time-kill assay. In vitro<\/jats:italic> results were then compared with the efficacy of the same dual or triple antibiotic combinations versus G. mellonella<\/jats:italic> larvae infected with P. aeruginosa<\/jats:italic>. G. mellonella<\/jats:italic> haemolymph burden of P. aeruginosa<\/jats:italic> was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro<\/jats:italic>. There was little correlation between combinations that were synergistic in vitro<\/jats:italic> and those that showed enhanced efficacy in vivo<\/jats:italic> versus infected G. mellonella<\/jats:italic> larvae. The most potent dual and triple combinations in vivo<\/jats:italic> were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit in vivo<\/jats:italic> compared with in vitro<\/jats:italic>. The therapeutic benefit arising from treatment with antibiotic combinations in vivo<\/jats:italic> correlated with reduced larval burden of P. aeruginosa<\/jats:italic>. This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using G. mellonella<\/jats:italic> to screen for novel antibiotic treatments that demonstrate efficacy in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1099\/jmm.0.074245-0","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T13:48:59Z","timestamp":1402926539000},"page":"945-955","source":"Crossref","is-referenced-by-count":56,"title":["A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa"],"prefix":"10.1099","volume":"63","author":[{"given":"Jessica","family":"Krezdorn","sequence":"first","affiliation":[{"name":"Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Adams","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Coote","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews KY16 9ST, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"r1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01231-08"},{"key":"r2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.1.43-48.2006"},{"key":"r3","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1985.00360090089015"},{"key":"r4","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02235-12"},{"key":"r5","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/19.3.321"},{"key":"r6","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-009-0774-9"},{"key":"r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.08.014"},{"key":"r8","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(89)80611-4"},{"key":"r9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2013.11.001"},{"key":"r10","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"Holm","year":"1979","journal-title":"Scand J Stat"},{"key":"r11","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00040-09"},{"key":"r12","doi-asserted-by":"publisher","DOI":"10.1086\/338782"},{"key":"r13","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.4.1306-1311.2005"},{"key":"r14","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg478"},{"key":"r15","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1360-5"},{"key":"r16","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.21.6.939"},{"key":"r17","doi-asserted-by":"publisher","DOI":"10.1007\/BF01695658"},{"key":"r18","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05041-11"},{"key":"r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2012.12.006"},{"key":"r20","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05996-11"},{"key":"r21","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1128\/AAC.40.8.1914","article-title":"Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test","volume":"40","author":"White","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"key":"r22","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-11-849"},{"key":"r23","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn400"}],"container-title":["Journal of Medical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.074245-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T08:14:41Z","timestamp":1601972081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.074245-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,1]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7,1]]}},"URL":"https:\/\/doi.org\/10.1099\/jmm.0.074245-0","relation":{},"ISSN":["0022-2615","1473-5644"],"issn-type":[{"value":"0022-2615","type":"print"},{"value":"1473-5644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,1]]}}}