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Title: | Fosfomycin plus Beta-lactams: Synergistic Bactericidal Combinations in Methicillin-resistant (MRSA) and Glycopeptide-Intermediate Resistant (GISA) Staphylococcus aureus Experimental Endocarditis |
Author: | Rio Fernández, Antonio del Garcia de la Mària, Cristina Entenza, José Manuel Gasch, Oriol Armero, Yolanda Soy Muner, Dolors Mestres Lucio, Carlos-Alberto Pericàs, Juan M. Falces Salvador, Carles Ninot, Salvador Almela, M. (Manel) Cervera, Carlos Gatell, José M. Moreno Camacho, Ma. Asunción Moreillon, Philippe Marco Reverté, Francesc Miró Meda, José M. Hospital Clínic Experimental Endocarditis Study Group |
Keywords: | Endocarditis Antibiòtics Endocarditis Antibiotics |
Issue Date: | 1-Jan-2016 |
Publisher: | American Society for Microbiology |
Abstract: | The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.Copyright © 2015, American Society for Microbiology. All Rights Reserved. |
Note: | Reproducció del postprint publicat a: https://doi.org/10.1128/AAC.02139-15 |
It is part of: | Antimicrobial Agents And Chemotherapy, 2015, vol 60, num 1, p. 478-486 |
URI: | http://hdl.handle.net/2445/184262 |
Related resource: | https://doi.org/10.1128/AAC.02139-15 |
ISSN: | 1098-6596 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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