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dc.contributor.authorDeSarno, Alexandra E
dc.contributor.authorParcell, Benjamin John
dc.contributor.authorCoote, Peter John
dc.date.accessioned2021-10-13T23:43:39Z
dc.date.available2021-10-13T23:43:39Z
dc.date.issued2020-10-14
dc.identifier.citationDeSarno , A E , Parcell , B J & Coote , P J 2020 , ' Repurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains of Klebsiella pneumoniae ' , Pathogens and Disease , vol. Advance Article . https://doi.org/10.1093/femspd/ftaa063en
dc.identifier.issn2049-632X
dc.identifier.otherPURE: 270640316
dc.identifier.otherPURE UUID: 77891074-bf28-49c1-a266-56b78037e136
dc.identifier.otherORCID: /0000-0001-5190-805X/work/83481752
dc.identifier.otherScopus: 85097967975
dc.identifier.otherWOS: 000604498400002
dc.identifier.urihttp://hdl.handle.net/10023/24137
dc.descriptionFunding: University of St Andrews.en
dc.description.abstractMulti-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections. Two MDR K. pneumoniae strains were employed, producing either the NDM-1 or KPC-3 carbapenemase. Efficacy of combinations of AZT with meropenem were compared with monotherapies against infections in Galleria mellonella larvae by measuring larval mortality and bacterial burden. The effect of the same combinations in vitro was determined via checkerboard and time-kill assays. In vitro, both K. pneumoniae strains were resistant to meropenem but were susceptible to AZT. In G. mellonella, treatment with either AZT or meropenem alone offered minimal therapeutic benefit against infections with either strain. In contrast, combination therapy of AZT with meropenem presented significantly enhanced efficacy compared to monotherapies. This was correlated with prevention of bacterial proliferation within the larvae but not elimination. Checkerboard assays showed that the interaction between AZT and meropenem was not synergistic but indifferent. In summary, combination therapy of AZT with meropenem represents a potential treatment for carbapenemase-producing MDR K. pneumoniae and merits further investigation.
dc.language.isoeng
dc.relation.ispartofPathogens and Diseaseen
dc.rightsCopyright © 2020 FEMS. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1093/femspd/ftaa063.en
dc.subjectKlebsiella pneumoniaeen
dc.subjectGalleria mellonellaen
dc.subjectWax-moth larvaeen
dc.subjectCombination therapyen
dc.subjectNDM1en
dc.subjectKPC3en
dc.subjectQR Microbiologyen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subject3rd-DASen
dc.subject.lccQRen
dc.subject.lccRMen
dc.titleRepurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains of Klebsiella pneumoniaeen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.Infection and Global Health Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.identifier.doihttps://doi.org/10.1093/femspd/ftaa063
dc.description.statusPeer revieweden
dc.date.embargoedUntil2021-10-14


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