title: Young Investigator Award. In vivo treatment of infected prosthetic graft material with urokinase: an animal model.
abstract: OBJECTIVE
  Pyogenic infection of vascular grafts represents a serious complication that may necessitate graft removal. If better treatment methods could be developed, perhaps some infected grafts could be salvaged and not removed. This study reports an animal model that evaluates the sterilization of contaminated vascular graft material implants with urokinase and antibiotics.
  
  
  METHODS
  Polytetrafluoroethylene (PTFE) implants were incubated overnight in a known concentration of bacteria (Staphylococcus epidermidis) and were then implanted subcutaneously into four groups of anesthetized hamsters. The first group (control) received no treatment. The second group received urokinase injections twice daily into each abscess. The third group received intraabscess urokinase and systemic gentamicin twice daily. The fourth group received only systemic gentamicin. The hamsters were killed after 1 week. The graft implants and surrounding tissues were excised and submitted for quantitative cultures.
  
  
  RESULTS
  With use of a cutoff value of 100 organisms per milliliter, below which the abscesses were considered noninfected, the following rates of noninfectivity were observed: group 1 (control), 5% noninfected; group 2 (urokinase only), 19.4%; group 3 (urokinase and gentamicin), 63.2%; and group 4 (gentamicin only), 32.5%. The noninfectivity rate of group 3 was significantly higher than that of all other groups combined (P < .001) and was significantly better than that of group 4 alone (P = .013).
  
  
  CONCLUSIONS
  The combination of intraabscess urokinase and systemic gentamicin is very synergistic in graft sterilization. Urokinase may assist in the degradation of both fibrin and the biofilm produced by S epidermidis, thus improving penetration of antibiotics and local host defense mechanisms.
authors.affiliation: Department of Radiology, University Hospitals of Cleveland, OH 44106.
authors.forename: D A
authors.initials: DA
authors.lastname: Nakamoto
authors.forename: M L
authors.initials: ML
authors.lastname: Rosenfield
authors.forename: J R
authors.initials: JR
authors.lastname: Haaga
authors.forename: K
authors.initials: K
authors.lastname: Merritt
authors.forename: P B
authors.initials: PB
authors.lastname: Sachs
authors.forename: M C
authors.initials: MC
authors.lastname: Hutton
authors.forename: R C
authors.initials: RC
authors.lastname: Graham
authors.forename: D Y
authors.initials: DY
authors.lastname: Rowland
mesh_terms: D000038:Abscess / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001363:Awards and Prizes; D001807:Blood Vessel Prosthesis; D006224:Cricetinae; D005839:Gentamicins / Q000627:therapeutic use; D011138:Polytetrafluoroethylene; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013212:Staphylococcus epidermidis; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005839:Gentamicins; D011138:Polytetrafluoroethylene; D014568:Urokinase-Type Plasminogen Activator