title: Efficacy of NVC-422 against Staphylococcus aureus biofilms in a sheep biofilm model of sinusitis.
abstract: BACKGROUND
  Bacterial biofilms are a major obstacle in management of recalcitrant chronic rhinosinusitis. NVC-422 is a potent, fast-acting, broad-spectrum, nonantibiotic, antimicrobial with a new mechanism of action effective against biofilm bacteria in in vitro conditions. The aim of this study was to investigate the safety and efficacy of NVC-422 as local antibiofilm treatment in a sheep model of rhinosinusitis.
  
  
  METHODS
  After accessing and occluding frontal sinus ostia in 24 merino sheep via staged endoscopic procedures, S. aureus clinical isolate was instilled in frontal sinuses. Following biofilm formation, ostial obstruction was removed and sinuses irrigated with 0.1% and 0.5% NVC-422 in 5 mM acetate isotonic saline at pH 4.0. Sheep were monitored for adverse effects and euthanized 24 hours after treatment. Frontal sinuses were assessed for infection and changes in mucosa after the treatment. S. aureus biofilms were identified with Baclight-confocal scanning microscopy protocol and the biofilm biomass assayed by applying the COMSTAT2 program to recorded image stacks.
  
  
  RESULTS
  After 2 irrigations with 0.1% NVC-422, S. aureus biofilm biomass was reduced when compared to control sinuses (p = 0.0001), though this effect was variable in samples. NVC-422 0.5% solution irrigations reduced biofilm even more significantly and consistently over all samples (p < 0.0001). NVC-422 0.5% was also more effective than 0.1% NVC-422, vehicle control, and normal saline sinus irrigations in reducing biofilm biomass (p < 0.05 for all subgroups). No adverse events were observed in sheep after sinus irrigations with 0.1% and 0.5% NVC-422 solutions.
  
  
  CONCLUSIONS
  NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.
authors.affiliation: Department of Surgery-Otolaryngology Head and Neck Surgery Adelaide University, South Australia.
authors.forename: Deepti
authors.initials: D
authors.lastname: Singhal
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekle
authors.forename: Dmitri
authors.initials: D
authors.lastname: Debabov
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Bez
authors.initials: B
authors.lastname: Khosrovi
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: Andrew
authors.initials: A
authors.lastname: Foreman
authors.forename: Peter-John
authors.initials: PJ
authors.lastname: Wormald
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002417:Cattle; D002908:Chronic Disease; D004195:Disease Models, Animal; D005626:Frontal Sinus / Q000187:drug effects* / Q000382:microbiology / Q000601:surgery; D006801:Humans; D007091:Image Processing, Computer-Assisted; D012220:Rhinitis / Q000188:drug therapy* / Q000209:etiology; D034561:Sheep, Domestic; D012852:Sinusitis / Q000188:drug therapy* / Q000209:etiology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013654:Taurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000890:Anti-Infective Agents; D013654:Taurine; C560851:NVC-422