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In vivo effect of cefazolin, daptomycin, and nafcillin in experimental endocarditis with a methicillin-susceptible Staphylococcus aureus strain showing an inoculum effect against cefazolin.


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Información de la publicación
Tipo de publicación

Científica

Tipología

Investigación y estudios

Medio de publicación

Impreso: Revista de divulgación científica

Resumen

Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla) producing, methicillin-susceptible Staphylococcus aureus (MSSA) show against cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed 24 hours after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than cefazolin in reducing CFU/g of vegetations, achieving mean log10 reductions compared to untreated rats of 7.1, 5.3, and 1.8, respectively (cefazolin versus daptomycin, P <0.0001; cefazolin versus nafcillin, P = 0.005; daptomycin versus nafcillin, P = 0.053). In addition, cefazolin was significantly more effective in reducing vegetation titers of TX0117c than TX0117 (mean log10 reduction of 1.4 versus 5.5, respectively, P = 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an in vivo consequence of the in vitro inoculum effect that some MSSA display against cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which cefazolin regained both in vitro and in vivo activity.

Autores

Nannini EC, Singh KV, Arias CA, Murray BE.

Registro ISSN

1098-6596 (Electronic)

SNIES Área

Immunology and Microbiology

SNIES Categoría

Microbiology

Fecha de publicación 24 de junio de 2013
Fecha de aceptación 09 de julio de 2013
Medio indexado (nombre)

Antimicrobial Agents and Chemotherapy

Bases de datos donde está referenciada

PubMed

English information
Title

In vivo effect of cefazolin, daptomycin, and nafcillin in experimental endocarditis with a methicillin-susceptible Staphylococcus aureus strain showing an inoculum effect against cefazolin.

Abstract

Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla) producing, methicillin-susceptible Staphylococcus aureus (MSSA) show against cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed 24 hours after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than cefazolin in reducing CFU/g of vegetations, achieving mean log10 reductions compared to untreated rats of 7.1, 5.3, and 1.8, respectively (cefazolin versus daptomycin, P <0.0001; cefazolin versus nafcillin, P = 0.005; daptomycin versus nafcillin, P = 0.053). In addition, cefazolin was significantly more effective in reducing vegetation titers of TX0117c than TX0117 (mean log10 reduction of 1.4 versus 5.5, respectively, P = 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an in vivo consequence of the in vitro inoculum effect that some MSSA display against cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which cefazolin regained both in vitro and in vivo activity.

Keywords

cefazolin, daptomycin,experimental endocarditis, Staphylococcus aureus

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