Efficacy of daptomycin-cloxacillin combination in experimental foreign-body infection due to methicillin-resistant Staphylococcus aureus.

Antimicrobial Agents and Chemotherapy
C GarrigósJ Ariza

Abstract

Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body weight/day) against difficult-to-treat infections, clinical failures and resistance appeared. Recently, the combination daptomycin-cloxacillin showed enhanced efficacy in clearing bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in humans, respectively) in combination with cloxacillin in a rat tissue cage infection model by MRSA and to compare its efficacy to that of daptomycin-rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin, especially in log phase. For in vivo studies, therapy was administered intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h, daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h. Daptomycin-rifampin was the best therapy (P < 0.05). Daptomycin 45 was the least effective treatment and did not protect against the emergence of resistant strains. There w...Continue Reading

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Citations

Jan 13, 2015·Expert Review of Anti-infective Therapy·Dolors Rodríguez-PardoBenito Almirante
Mar 13, 2014·Journal of Internal Medicine·W Zimmerli
Apr 1, 2016·Trials·Steven Y C TongUNKNOWN CAMERA2 study group and the Australasian Society for Infectious Diseases Clinical Research Network
Oct 27, 2015·Annals of the New York Academy of Sciences·Truc T TranCesar A Arias
Nov 4, 2015·Antimicrobial Agents and Chemotherapy·A del RíoUNKNOWN Hospital Clinic Experimental Endocarditis Study Group
Aug 24, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Galoz KanetiAmram Mor

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