A novel approach to reduce catheter-related infection using sustained-release basic fibroblast growth factor for tissue regeneration in mice.

Catheter-related infection is one of the most serious complications. Microbes migrate along the catheter (the foreign material) from the wound at the insertion-site, leading to catheter-related infection. Basic fibroblast growth factor (bFGF) is a potent mitogen that promotes the growth and regeneration of organs and tissues in vivo. Catheter-related bacterial invasion was simulated by the invasion of inoculated bacteria into a transplanted foreign material. Sterile Dacron sheets (foreign materials) were implanted on the subcutis of 96 male mice (C57BL/6) randomized into four groups (n = 24 per group). Group A: Dacron sheets only; Group B: Dacron sheets treated with a plain gelatin hydrogel sheet; Group C: Dacron sheets treated with free bFGF (50 microg); Group D: Dacron sheets treated with sustained-release bFGF (50 microg). On day 7, "detachment test" (to measure the force needed to pull out the Dacron sheet) and microscopic evaluations were performed, and the tissue immediately above the Dacron sheet was inoculated with methicillin-resistant Staphylococcus aureus (MRSA) 1 x 10(6) colony-forming units. The total energy needed for pulling out the implanted Dacron sheet in Group D was significantly higher than other three groups (P < 0.01). Group D had a large granulation tissue area containing a large amount of collagen tissue and vessels microscopically. Two days after the MRSA inoculation, the number of MRSA in the Dacron sheet of Group D was smallest. Pretreatment with sustained-release form of bFGF promoted tissue regeneration and reduced catheter-related bacterial invasion, indicating a useful adjuvant for reducing catheter-related infection.

Sustained-release vancomycin sheet may help to prevent prosthetic graft methicillin-resistant Staphylococcus aureus infection.

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.