title: 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 long-term 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.
authors.affiliation: Cardiology Department, Hippocration General Hospital, Athens, Greece. iskiadas@med.uoa.gr
authors.forename: Ioannis
authors.initials: I
authors.lastname: Skiadas
authors.forename: Angelos
authors.initials: A
authors.lastname: Pefanis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: Aspasia
authors.initials: A
authors.lastname: Kyroudi
authors.forename: Helen
authors.initials: H
authors.lastname: Triantafyllidi
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001021:Aortic Valve / Q000187:drug effects / Q000473:pathology*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004452:Echocardiography; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D024841:Fluoroquinolones; D006801:Humans; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D003907:Dexamethasone; D008712:Methicillin; D000077266:Moxifloxacin