Efficacy of NVC-422 against Staphylococcus aureus biofilms in a sheep biofilm model of sinusitis

Deepti Singhal, A Jekle, D Debabov, L Wang, B Khosrovi, M Anderson, Andrew Foreman, Peter Wormald

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    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. © 2012 ARS-AAOA, LLC Conclusion: NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.

    Original languageEnglish
    Pages (from-to)309-315
    Number of pages7
    JournalInternational Forum of Allergy and Rhinology
    Volume2
    Issue number4
    DOIs
    Publication statusPublished - 2012

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    Singhal, D., Jekle, A., Debabov, D., Wang, L., Khosrovi, B., Anderson, M., Foreman, A., & Wormald, P. (2012). Efficacy of NVC-422 against Staphylococcus aureus biofilms in a sheep biofilm model of sinusitis. International Forum of Allergy and Rhinology, 2(4), 309-315. https://doi.org/10.1002/alr.21038