Efficacy of ceftaroline against methicillin-susceptible Staphylococcus aureus exhibiting the cefazolin high-inoculum effect in a rat model of endocarditis

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dc.contributor.authorSingh, Kavindra V.
dc.contributor.authorTran, Truc T.
dc.contributor.authorNannini, Esteban
dc.contributor.authorTam, Vincent
dc.contributor.authorArias, Cesar A
dc.contributor.authorMurray, Barbara
dc.date.accessioned2020-04-22T16:02:01Z
dc.date.available2020-04-22T16:02:01Z
dc.date.issued2017
dc.description.abstractenglishCertain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in high-inoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A β-lactamase (βla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its βla-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to ≥128 μg/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P = 0.001; CPT versus NAF, P = 0.9830). Both CFZ and CPT were efficacious against the βla-cured derivative, TX0117c, compared to time zero (t0) (P = <0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for high-inoculum infections caused by MSSA exhibiting the CFZ InE.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://dx.doi.org/10.1128%2FAAC.00324-17
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1098-6596
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2319
dc.language.isoeng
dc.publisherAmerican Society for Microbiologyspa
dc.publisher.journalAntimicrobial Agents and Chemotherapyspa
dc.relation.ispartofseriesAntimicrobial Agents and Chemotherapy, 1098-6596, Vol. 61, Nro. 7, 2017, p. 1-9spa
dc.relation.urihttps://aac.asm.org/content/61/7/e00324-17
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf443
dc.rights.creativecommons2017
dc.rights.localAcceso cerradospa
dc.subject.decsInfecciones Bacterianasspa
dc.subject.decsAntibacterianosspa
dc.subject.decsAntibióticos penicilinosspa
dc.subject.keywordsβ-lactamasespa
dc.subject.keywordsStaphylococcus aureusspa
dc.subject.keywordsCeftarolinespa
dc.subject.keywordsEndocarditisspa
dc.titleEfficacy of ceftaroline against methicillin-susceptible Staphylococcus aureus exhibiting the cefazolin high-inoculum effect in a rat model of endocarditisspa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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