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

Abstract

Although the beneficial effects of dexamethasone have frequently been investigated in various serious-infection settings, insufficient data on valve histology and cardiac function for infective endocarditis are available. The efficacy of moxifloxacin for the treatment of 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. Groups B and C consisted of 11 and 23 subjects, respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. Group D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25 mg/kg of body weight twice a day intravenously). The group B animals were sacrificed a day after the completion of treatment, and group C and D animals were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological, and echocardiographic evaluation of the longterm effects of glucocorticoids. No differences in survival, sterilization rates, or inflammatory infiltration and calcification of valve tissue were observed among the treated groups. However, the degrees of valve damage and collagenization were significantly worse, the fibroblast content was higher, and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all groups, P < 0.05). We concluded that dexamethasone treatment for experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.

Successful treatment with moxifloxacin of experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA)

“…These results are similar to another experimental study where MXF given for 5 days at the same dose as in the present research sterilised all but one vegetation in a rabbit model of endocarditis due to MSSA, whilst no relapses of endocarditis were observed [21]. It is also important to mention that in all experiments almost all of the treated animals had sterile vegetations after 3-5 days of treatment [21]. In a previous study of experimental endocarditis, MXF was active against MXF-sensitive (MIC = 0.12 and 0.5 mg/L) strains of ciprofloxacin-sensitive (MIC = 0.5 mg/L) and ciprofloxacin-resistant (MIC = 8 mg/L) MRSA [11].…”

“…Interestingly, prolongation of treatment with MXF from 4 days to 5 days resulted in a 100% sterilisation rate of vegetations, with no relapse of endocarditis even 5 days after the cessation of treatment. These results are similar to another experimental study where MXF given for 5 days at the same dose as in the present research sterilised all but one vegetation in a rabbit model of endocarditis due to MSSA, whilst no relapses of endocarditis were observed [21]. It is also important to mention that in all experiments almost all of the treated animals had sterile vegetations after 3-5 days of treatment [21].…”

“…In the previously mentioned experimental study, the concentrations of MXF in vegetations 12 h after the last dose of a 5-day (10 doses) treatment course were 2.87 ± 0.75 mg/kg (n = 4) [21]. In a pharmacodynamic study using fibrin clots infected with S. aureus, the initial inoculum of 5.56-7.32 log 10 CFU/g of clot reduced to undetectable levels 18 h after a human kinetics simulated dose of MXF [28].…”

“…Treatment was initiated 24 h after bacterial challenge. The doses of antibiotics were chosen because they have been used in previous experimental studies of endocarditis in rabbits [19][20][21]. Animals surviving for the duration of the experiment were sacrificed by bolus intravenous injection of sodium phenobarbital (30 mg/kg).…”

Influence of Dexamethasone on Atrial Ion Currents and Their Early Ionic Tachycardia-induced Electrical Remodeling in Rabbits

“…To better compare dexamethasone induced alterations in our current experiments, results of our previous experiments are recapitulated. "Dexamethasone only"-group (DO) was treated like CO but with additional dexamethasone treatment in a physiologically relevant dose (0.5 mg/kg bodyweight dexamethasone intramuscular every 24 hours [8] for 7 days before removal of the heart). Dexamethasone dosage was in the same range as in clinical trials examining a potential prevention of atrial fibrillation after cardiac surgery [9,10].…”