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Antimicrob. Agents Chemother. doi:10.1128/AAC.01376-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis due to Staphylococcus aureus

Fourth Department of Internal Medicine, University of Athens, School of Medicine, University General Hospital ‘Attikon’, Athens, Greece; Cardiology Department, Hippocration General Hospital, Athens, Greece; Third Department of Internal Medicine, University of Athens, School of Medicine, Sotiria General Hospital for Chest Diseases, Athens, Greece; Experimental-Research Department of ELPEN-Pharma, Athens, Greece; Department of Histology and Embryology, University of Athens, School of Medicine, Athens, Greece; Second Department of Cardiology, University of Athens, School of Medicine, University General Hospital ‘Attikon’, Athens, Greece

^* To whom correspondence should be addressed. Email: iskiadas{at}med.uoa.gr.

	Abstract

Although the beneficial effects of dexamethasone have been frequently investigated in various serious infectious settings, insufficient data is available on valve histology and cardiac function for infective endocarditis. The efficacy of moxifloxacin in experimental aortic valve endocarditis due to methicillin-susceptible Staphylococcus aureus and the long term effects of dexamethasone were evaluated in the current study. Sixty-eight rabbits were randomly assigned to four groups: A, B, C, and D. Group A consisted of 18 animals and functioned as a control group. B and C consisted of 11 and 23 subjects respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25mg/kg bid, iv). In group B, the animals were sacrificed a day after the completion of treatment, and in groups C and D were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological and echocardiographic evaluation of the long term effects of glucocorticoids. No differences in survival, sterilization rates and inflammatory infiltration and calcification of valve tissue were observed between the treated groups. However, the degrees of valve damage and collagenization were significantly worse, fibroblast content was higher and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all p<0.05). It was concluded that dexamethasone in experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.