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dc.contributor.authorSiriyong, Thanyaluck
dc.contributor.authorMurray, Rachael M.
dc.contributor.authorBidgood, Lucy E.
dc.contributor.authorYoung, Simon A.
dc.contributor.authorWright, Florence
dc.contributor.authorParcell, Benjamin J.
dc.contributor.authorVoravuthikunchai, Supayang Piyawan
dc.contributor.authorCoote, Peter J.
dc.date.accessioned2019-07-01T12:30:02Z
dc.date.available2019-07-01T12:30:02Z
dc.date.issued2019-06-24
dc.identifier.citationSiriyong , T , Murray , R M , Bidgood , L E , Young , S A , Wright , F , Parcell , B J , Voravuthikunchai , S P & Coote , P J 2019 , ' Dual β-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection : enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition ' , Scientific Reports , vol. 9 , 9098 . https://doi.org/10.1038/s41598-019-45550-zen
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 259267007
dc.identifier.otherPURE UUID: 069239d5-5b7c-40be-9f2c-eca45a2b7262
dc.identifier.otherScopus: 85067850417
dc.identifier.otherORCID: /0000-0003-1072-905X/work/59222245
dc.identifier.otherORCID: /0000-0001-5190-805X/work/59222297
dc.identifier.otherWOS: 000472597400001
dc.identifier.urihttp://hdl.handle.net/10023/18013
dc.descriptionS.V. and T.S. were supported by Thailand Research Fund Senior Research Scholar (Grant Number RTA6180006). R.M. and P.C. were funded by University of St Andrews.en
dc.description.abstractThe aim of the study was to determine the efficacy of dual β-lactam combination treatments derived from eight approved drugs against Galleria mellonella larvae infected with MDR strains of P. aeruginosa. Carbapenem-resistant P. aeruginosa NCTC 13437 and an unrelated clinical isolate were used to infect G. mellonella larvae and the efficacy of twenty-eight dual β-lactam combination therapies were compared to their constituent monotherapies. For the most potent combinations identified, penicillin-binding protein (PBP) inhibition profiles were measured and compared with each constituent antibiotic. Five of the dual β-lactam combinations resulted in greater than 70% survival of infected G. mellonella. Two combinations showed potent, enhanced efficacy versus both strains − ceftazidime + meropenem and aztreonam + meropenem. Comparison of PBP inhibition profiles revealed that the enhanced efficacy of these two dual β-lactam combinations could not be explained by more potent inhibition of PBPs or inhibition of a broader range of PBPs. A possible contribution to the enhanced efficacy of the combinations could be stimulation of innate immunity via increased haemocyte numbers compared to their constituent monotherapies. Combinations of β-lactam antibiotics show promise in overcoming MDR P. aeruginosa and are worthy of additional study and development.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsCopyright © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectQR Microbiologyen
dc.subjectNDASen
dc.subject.lccQRen
dc.titleDual β-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection : enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibitionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1038/s41598-019-45550-z
dc.description.statusPeer revieweden


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