title: Prevention of vascular graft infections with antibiotic graft impregnation prior to implantation: in vitro comparison between daptomycin, rifampin and nebacetin.
abstract: OBJECTIVE
  To compare the in vitro efficacy of graft impregnation with nebacetin versus rifampin versus daptomycin against vascular graft infections caused by Staphylococcus epidermidis and Staphylococcus aureus and nebacetin versus rifampin against Pseudomonas aeruginosa and Escherichia coli.
  
  
  METHODS
  Twenty-three Dacron-grafts (1 cm2) for each micro-organism were microbiologically tested and eight grafts per antibiotic underwent viability tests against human umbilical vein endothelial cells (ECs). Fifteen grafts (5/antibiotic agent) underwent 15 min impregnation and contamination with 4 ml bacterial solution (optical density (OD (600 nm)): 0.20 ± 0.02). After 24-h-incubation, all grafts were washed with phosphate-buffered saline and underwent sonification to release viable adherent bacteria. OD (600 nm) of the solution was measured. Afterwards, six 1:10 dilution steps took place and colony-forming units (CFUs) were counted.
  
  
  RESULTS
  Nebacetin showed comparable efficacy to daptomycin against Gram-positive bacteria. Both eradicated more efficiently S. epidermidis than rifampin (daptomycin:0, rifampin:5 ± 7.3, nebacetin:0 CFU ml(-1), P = 0.0003). All antibiotics showed comparable antibacterial activity against S. aureus. Nebacetin was more efficient than rifampin to eradicate Gram-negative organisms (P. aeruginosa: rifampin:1308 ± 252, nebacetin:8 ± 8 CFU ml(-1), P = 0.01, E. coli: rifampin:294 ± 159, nebacetin:0.2 ± 0.5 CFU ml(-1), P = 0.001), while only rifampin was toxic against ECs (daptomycin:30.88 ± 5.44, rifampin:5.13 ± 5.08, nebacetin:28.50 ± 3.82 ECs/field, P = 0.0003).
  
  
  CONCLUSIONS
  Nebacetin showed excellent in vitro antibacterial activity against both Gram-positive and -negative pathogens representing an effective candidate for vascular graft impregnation.
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. Bisdas.Theodosios@MH-Hannover.de
authors.forename: T
authors.initials: T
authors.lastname: Bisdas
authors.forename: E
authors.initials: E
authors.lastname: Beckmann
authors.forename: G
authors.initials: G
authors.lastname: Marsch
authors.forename: K
authors.initials: K
authors.lastname: Burgwitz
authors.forename: M
authors.initials: M
authors.lastname: Wilhelmi
authors.forename: C
authors.initials: C
authors.lastname: Kuehn
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.forename: O E
authors.initials: OE
authors.lastname: Teebken
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001414:Bacitracin / Q000494:pharmacology / Q000627:therapeutic use; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002478:Cells, Cultured; D017576:Daptomycin / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009355:Neomycin / Q000494:pharmacology / Q000627:therapeutic use; D016459:Prosthesis-Related Infections / Q000209:etiology* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use; D013211:Staphylococcus aureus / Q000187:drug effects*; D013212:Staphylococcus epidermidis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001414:Bacitracin; C003903:Nebacetin; D009355:Neomycin; D017576:Daptomycin; D012293:Rifampin