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Title: | Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis |
Author: | García de la Mària, Cristina Gasch, Oriol Castañeda, Ximena García González, Javier Soy, Dolors Cañas, Maria Alexandra Ambrosioni, Juan Almela, Manel Pericàs, Juan M. Téllez, Adrián Falces Salvador, Carles Hernández-Meneses, Marta Sandoval, Elena Quintana, Eduard Vidal, Barbara Tolosana, José M. (José María) Fuster, David Llopis, Jaume Moreno, Asuncion Marco, Francesc Miró, Jose M. Hospital Clínic Endocarditis Study Group |
Keywords: | Endocarditis Medicaments antibacterians Staphylococcus aureus Endocarditis Antibacterial agents Staphylococcus aureus |
Issue Date: | Dec-2020 |
Publisher: | Oxford University Press |
Abstract: | Background: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE). Methods: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h). Results: At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC. Conclusions: The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1093/jac/dkaa354 |
It is part of: | Journal of Antimicrobial Chemotherapy, 2020, vol. 75, num. 12, p. 3586-3592 |
URI: | http://hdl.handle.net/2445/184344 |
Related resource: | https://doi.org/10.1093/jac/dkaa354 |
ISSN: | 0305-7453 |
Appears in Collections: | Articles publicats en revistes (ISGlobal) Articles publicats en revistes (Genètica, Microbiologia i Estadística) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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