title: Chitosan sponges for local synergistic infection therapy: a pilot study.
abstract: BACKGROUND
  Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment.
  
  
  OBJECTIVE
  In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels.
  
  
  METHODS
  To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n=1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n=3) and the drug release profile from a chitosan sponge device (n=5).
  
  
  RESULTS
  With an FIC index<0.5, the combination of CHX+VAN exhibited synergism against S aureus. CHX concentrations≥3.91 μg/mL resulted in fibroblast viability decrease, whereas the combination of CHX+VAN did not decrease fibroblast viability until their concentrations reached ≥7.81 μg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5.
  
  
  CONCLUSIONS
  CHX+VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth.
  
  
  CONCLUSIONS
  The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.
authors.affiliation: Department of Biomedical Engineering, University of Memphis, 328A Engineering Technology Building, Memphis, TN, 38152, USA, jksmith@memphis.edu.
authors.forename: J Keaton
authors.initials: JK
authors.lastname: Smith
authors.forename: Abteen R
authors.initials: AR
authors.lastname: Moshref
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Jennings
authors.forename: Harry S
authors.initials: HS
authors.lastname: Courtney
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D048271:Chitosan / Q000008:administration & dosage*; D017576:Daptomycin / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D010865:Pilot Projects; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D014640:Vancomycin; D000583:Amikacin; D048271:Chitosan; D017576:Daptomycin