title: Limitations in the use of rifampicin-gelatin grafts against virulent organisms.
abstract: OBJECTIVE
  Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model.
  
  
  METHODS
  Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone.
  
  
  RESULTS
  In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 +/- 0.3 mm, 36.0 +/- 0.2 mm, and 11.8 +/- 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 +/- 1.1 mm and 7.6 +/- 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 +/- 0.2 mm and 18.5 +/- 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitory concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection.
  
  
  CONCLUSIONS
  These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitory concentration MRSA strains or poor susceptibility.
authors.affiliation: Department of Surgery, Asahikawa Medical University, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Koshiko
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasajima
authors.forename: Senichi
authors.initials: S
authors.lastname: Muraki
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Azuma
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Kaoru
authors.initials: K
authors.lastname: Chiba
authors.forename: Mineji
authors.initials: M
authors.lastname: Tachibana
authors.forename: Masashi
authors.initials: M
authors.lastname: Inaba
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D019917:Blood Vessel Prosthesis Implantation; D004285:Dogs; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000517:prevention & control*; D005780:Gelatin; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013997:Time Factors
chemical_list: D000904:Antibiotics, Antitubercular; D005780:Gelatin; D012293:Rifampin