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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
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dc.contributor.author | Siriyong, Thanyaluck | |
dc.contributor.author | Murray, Rachael M. | |
dc.contributor.author | Bidgood, Lucy E. | |
dc.contributor.author | Young, Simon A. | |
dc.contributor.author | Wright, Florence | |
dc.contributor.author | Parcell, Benjamin J. | |
dc.contributor.author | Voravuthikunchai, Supayang Piyawan | |
dc.contributor.author | Coote, Peter J. | |
dc.date.accessioned | 2019-07-01T12:30:02Z | |
dc.date.available | 2019-07-01T12:30:02Z | |
dc.date.issued | 2019-06-24 | |
dc.identifier | 259267007 | |
dc.identifier | 069239d5-5b7c-40be-9f2c-eca45a2b7262 | |
dc.identifier | 85067850417 | |
dc.identifier | 000472597400001 | |
dc.identifier.citation | Siriyong , 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-z | en |
dc.identifier.issn | 2045-2322 | |
dc.identifier.other | ORCID: /0000-0003-1072-905X/work/59222245 | |
dc.identifier.other | ORCID: /0000-0001-5190-805X/work/59222297 | |
dc.identifier.uri | https://hdl.handle.net/10023/18013 | |
dc.description | S.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.abstract | The 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.extent | 13 | |
dc.format.extent | 2363510 | |
dc.language.iso | eng | |
dc.relation.ispartof | Scientific Reports | en |
dc.subject | QR Microbiology | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject.lcc | QR | en |
dc.title | 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 | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.identifier.doi | 10.1038/s41598-019-45550-z | |
dc.description.status | Peer reviewed | en |
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