The Efficacy of Topical Antibiofilm Agents in a Sheep Model of Rhinosinusitis

Abstract
Background Biofilms have been shown to be resistant to conventional antibiotic treatment. This study uses a sheep biofilm model developed by our department to investigate several novel topical anti-biofilm treatments. Methods Staphylococcal biofilms were grown in 54 sheep frontal sinuses over 8 days: Each sinus was randomized to (1) no intervention, (2) single mupirocin flush, (3) regular 12-hourly mupirocin flushes for 5 days, (4) Citric Acid Zwitterionic Surfactant (CAZS) via hydrodebrider, (5) gallium nitrate, (6) CAZS with gallium nitrate, (7) CAZS with mupirocin, and (8) saline regular flushes. Sheep were sacrificed and the sinus mucosa harvested 1 or 8 days after treatment to assess treatment and any biofilm regrowth. Confocal scanning laser microscopy was used to confirm the presence or absence of biofilms, and the extent of biofilm reduction was quantitated using fluorescent in situ hybridization and colony forming unit counts. Results In the control sheep biofilm coverage averaged 31.7%. Saline and mupirocin b.d. washes for 5 days had 23% and 0.84% coverage, respectively, when harvested on day 8. A single mupirocin and gallium wash had 7.7% and 16.2% on day 1 and 5.88% and 16.0% on day 8. CAZS with hydrodebrider had 6.66% on day 1 but 21.95% on day 8 whereas CAZS with hydodebrider and gallium had 13.3% on day 8. Conclusion This study shows that regular treatment with mupirocin produced the most marked reduction in biofilm surface area coverage (0.84% and 1.25%) with sustained effects over the 8-day follow-up period.