title: Sustained-release vancomycin sheet may help to prevent prosthetic graft methicillin-resistant Staphylococcus aureus infection.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the effectiveness of a sustained-release sheet with vancomycin (VCM) to prevent prosthetic graft infection.
  
  
  METHODS
  VCM was incorporated into a poly-L-lactide-co-caprolactone (PLCA) sheet (VCM-PLCA). The release profile of VCM from the VCM-PLCA sheet and the tissue concentration of VCM released in vivo were examined. To assess the antibacterial effect of the VCM-PLCA sheet, a sterile Dacron sheet was implanted into 96 male mice (C57BL/6), who were randomly divided into four groups of 24 each and treated as follows: no treatment (group A, control group), a local bolus injection of an aqueous solution of VCM (group B), a plain PLCA sheet (group C), and a VCM-PLCA sheet (group D). After the treatment, methicillin-resistant Staphylococcus aureus (MRSA) (1 x 10(6) colony forming units) was inoculated onto the Dacron graft surface. The Dacron grafts were retrieved on days 3, 7, 10, and 14 after the implantation, and the number of MRSA in the Dacron grafts was counted.
  
  
  RESULTS
  VCM was slowly released from the VCM-PLCA sheet over 2 weeks in vivo, and the mean in vivo concentrations of VCM in the tissue around a VCM-PLCA sheet were 7.95, 26.39, 13.87, 12.51, 8.36, and 10.33 mug/mL (the minimum inhibitory concentration of VCM against MRSA is 2.0 mug/ml), at 1, 2, 5, 7, 10, and 14 days after the implantation, respectively. MRSA colonization on the cultivated agar plates was detected in all samples from groups A, B, and C at any postoperative time points. In contrast, some samples were negative for bacterial cultures in group D (2, 3, 1, and 2 samples out of 6 samples each on days 3, 7, 10, and 14 after the implantation, respectively). At all time points, the number of MRSA bacteria in the implanted Dacron graft in group D was by far the lowest (P < .01 at each time point).
  
  
  CONCLUSIONS
  The sustained-release sheet with VCM appears to be effective for the reduction of subcutaneous prosthetic graft infection.
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Arai
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nomura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Inoue
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaneda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kamitani
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001807:Blood Vessel Prosthesis / Q000382:microbiology*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D011091:Polyesters / Q000737:chemistry; D011093:Polyethylene Terephthalates; D016459:Prosthesis-Related Infections / Q000473:pathology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000473:pathology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D040521:Subcutaneous Tissue / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011093:Polyethylene Terephthalates; D014640:Vancomycin; C062968:lactide-caprolactone copolymer