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dc.contributor.authorErsoy, Selvi C
dc.contributor.authorRose, Warren E
dc.contributor.authorPatel, Robin
dc.contributor.authorProctor, Richard A
dc.contributor.authorChambers, Henry F
dc.contributor.authorHarrison, Ewan M
dc.contributor.authorPak, Youngju
dc.contributor.authorBayer, Arnold S
dc.date.accessioned2021-10-30T01:12:54Z
dc.date.available2021-10-30T01:12:54Z
dc.date.issued2021-09-09
dc.identifier.citationAntibiotics (Basel, Switzerland), volume 10, issue 9
dc.identifier.issn2079-6382
dc.identifier.otherPMC8469475
dc.identifier.other34572671
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330089
dc.description.abstractAntimicrobial susceptibility testing (AST) is routinely used to establish predictive antibiotic resistance metrics to guide the treatment of bacterial pathogens. Recently, a novel phenotype termed "bicarbonate (NaHCO3)-responsiveness" was identified in a relatively high frequency of clinical MRSA strains, wherein isolates demonstrate in vitro "susceptibility" to standard β-lactams (oxacillin [OXA]; cefazolin [CFZ]) in the presence of NaHCO3, and in vivo susceptibility to these β-lactams in experimental endocarditis models. We investigated whether a targeted phenotypic-genotypic screening of MRSA could rule in or rule out NaHCO3 susceptibility upfront. We studied 30 well-characterized clinical MRSA bloodstream isolates, including 15 MIC-susceptible to CFZ and OXA in NaHCO3-supplemented Mueller-Hinton Broth (MHB); and 15 MIC-resistant to both β-lactams in this media. Using a two-tiered strategy, isolates were first screened by standard disk diffusion for susceptibility to a combination of amoxicillin-clavulanate [AMC]. Isolates then underwent genomic sequence typing: MLST (clonal complex [CC]); agr; SCCmec; and mecA promoter and coding region. The combination of AMC disk susceptibility testing plus mecA and spa genotyping was able to predict MRSA strains that were more or less likely to be NaHCO3-responsive in vitro, with a high degree of sensitivity and specificity. Validation of this screening algorithm was performed in six strains from the overall cohort using an ex vivo model of endocarditis. This ex vivo model recapitulated the in vitro predictions of NaHCO3-responsiveness vs. nonresponsiveness above in five of the six strains.
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2079-6382
dc.sourcenlmid: 101637404
dc.subjectGenome sequencing
dc.subjectMethicillin-resistant Staphylococcus Aureus (Mrsa)
dc.subjectAntimicrobial Susceptibility Testing (Ast)
dc.subjectSodium Bicarbonate (Nahco3)
dc.subjectΒ-Lactam Susceptibility
dc.titleA Combined Phenotypic-Genotypic Predictive Algorithm for In Vitro Detection of Bicarbonate: β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA).
dc.typeArticle
dc.date.updated2021-10-30T01:12:53Z
prism.publicationNameAntibiotics (Basel)
dc.identifier.doi10.17863/CAM.77533
dcterms.dateAccepted2021-08-30
rioxxterms.versionofrecord10.3390/antibiotics10091089
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidErsoy, Selvi C [0000-0002-8792-2061]
dc.contributor.orcidRose, Warren E [0000-0001-5012-5993]
dc.contributor.orcidBayer, Arnold S [0000-0003-1968-0192]
dc.identifier.eissn2079-6382
pubs.funder-project-idNIH HHS (AI146078, AI132627)
cam.issuedOnline2021-09-09


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International