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dc.contributor.author
Singh, Kavindra V.
dc.contributor.author
Tran, Truc T.
dc.contributor.author
Nannini, Esteban
dc.contributor.author
Tam, Vincent H.
dc.contributor.author
Arias, Cesar A.
dc.contributor.author
Murray, Barbara E.
dc.date.available
2018-06-28T17:52:32Z
dc.date.issued
2017-07
dc.identifier.citation
Singh, Kavindra V.; Tran, Truc T.; Nannini, Esteban; Tam, Vincent H.; Arias, Cesar A.; et al.; Efficacy of ceftaroline against methicillin-susceptible Staphylococcus aureus exhibiting the cefazolin high-inoculum effect in a rat model of endocarditis; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 61; 7; 7-2017; 1-11
dc.identifier.issn
0066-4804
dc.identifier.uri
http://hdl.handle.net/11336/50422
dc.description.abstract
Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in highinoculum 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 highinoculum infections caused by MSSA exhibiting the CFZ InE.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Ceftaroline
dc.subject
Endocarditis
dc.subject
Staphylococcus Aureus
dc.subject
Β-Lactamase
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Efficacy of ceftaroline against methicillin-susceptible Staphylococcus aureus exhibiting the cefazolin high-inoculum effect in a rat model of endocarditis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-28T14:06:45Z
dc.journal.volume
61
dc.journal.number
7
dc.journal.pagination
1-11
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Singh, Kavindra V.. University of Texas; Estados Unidos
dc.description.fil
Fil: Tran, Truc T.. University of Texas; Estados Unidos
dc.description.fil
Fil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: Tam, Vincent H.. University Of Houston; Estados Unidos
dc.description.fil
Fil: Arias, Cesar A.. University of Texas; Estados Unidos. Universidad El Bosque; Colombia
dc.description.fil
Fil: Murray, Barbara E.. University of Texas; Estados Unidos
dc.journal.title
Antimicrobial Agents and Chemotherapy
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.00324-17
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/61/7/e00324-17


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