Antibiotic eluting sinus stents

Abstract

Objectives: Chronic rhinosinusitis (CRS) is a multifactorial disease affecting up to 16% of the United States population and disproportionately affecting the cystic fibrosis (CF) patient population. Despite treating the underlying infection, the use of systemic antibiotics has shown little efficacy in alleviation of symptom burden. This review seeks to discuss recent research on novel antibiotic eluting stent therapy in vitro and within animal models as well as the factors that contribute to its efficacy.

Data sources: PubMed literature review.

Review methods: A review of all published literature related to antibiotic eluting sinus stents was conducted to integrate and summarize this innovative approach to chronic sinus infections.

Results: Placement of the ciprofloxacin sinus stent (CSS) and ciprofloxacin-ivacaftor sinus stent (CISS) exhibited improvement in endoscopic and radiographic findings in rabbit CRS models. While the CSS showed an overall trend toward improvement in microscopic findings and a reduction in biofilm mass, there remained a significant quantity of planktonic bacteria due to antibiotic depletion from an initial burst release in the first 48 hours of stent placement. The CISS and ciprofloxacin-azithromycin sinus stents (CASSs) exhibited controlled antibiotic release over the study period leading to greatly reduced planktonic bacterial load and biofilm mass. In vitro studies indicate that CASS may be just as efficacious at reducing biofilm mass.

Conclusion: Antibiotic eluting sinus stents show significant promise as a novel therapeutic strategy for CRS. The CISS may have particular promise for the CF patient population by addressing both the infectious and genetic components of disease. Animal studies demonstrate significant promise for translation into human studies. Human clinical trials are warranted to determine the efficacy of antibiotic sinus stents in human patients.

Level of evidence: NA.

Keywords: antibiotic stent; azithromycin; biofilm; chronic rhinosinusitis; ciprofloxacin; cystic fibrosis; ivacaftor; sinus stent; sinusitis; stent.

FIGURE 1

In vitro effects of the ciprofloxacin sinus stent on PAO1 biofilms. Utilizing crystal violet staining with optical density spectrometer analysis at 590 nm, CSS was shown to reduce biofilm mass to ~10% of the level of control. This is comparable to levels of biofilm found when grown in the presence of 1.0 μg/mL of ciprofloxacin. # = significance compared to control group. Adapted from Reference 57. CSS, ciprofloxacin sinus stent

FIGURE 2

Effects of ciprofloxacin + ivacaftor on PAO1 biofilms. Utilizing crystal violet staining with optical density spectrometer analysis at 590 nm, a statistically significant overall reduction of biofilm mass was observed at 0.01 μg/mL and 0.05 mg/mL of ciprofloxacin with the addition of 8 and 16 μg/mL of ivacaftor. * = statistical significance compared to control. # = statistical significance within a ciprofloxacin group. Adapted from Reference 69. NS, not significant

FIGURE 3

Scanning electron microscopy of the ciprofloxacin‐ivacaftor sinus stent. A, Aerial view of stent surface. B, Stent prior to use. C, Stent after 21 days of in vitro use. *: Inner (ciprofloxacin) layer of stent. **: Outer (ivacaftor) layer of stent. Arrows: Thickness of stent. Adapted from Reference 70

FIGURE 4

Comparison of the CSS (left) vs the CISS (right). The CSS exhibited an initial burst release phenomenon with 30% of ciprofloxacin released by day 2. Release rate slowed to <50% after day 7. The CISS showed sustained release of ciprofloxacin and ivacaftor over 21 days without an initial burst release. Adapted from References 55 and 70. CISS, ciprofloxacin‐ivacaftor sinus stent; CSS, ciprofloxacin sinus stent

FIGURE 5

Axial micro‐CT findings of the CISS. Left: CT scan of the rabbit sinus with near complete opacification of the left maxillary sinus prior to stent placement. Middle: Continued opacification after 3 weeks of sham stent placement. Right: Radiograph showing reduced opacification after 3 weeks of CISS stent placement. Adapted from Reference 74. CISS, ciprofloxacin‐ivacaftor sinus stent; CT, computed tomographic

FIGURE 6

Release profiles of ciprofloxacin and azithromycin in the CASS vs CSS. A, Release profile of ciprofloxacin in the CASS vs CSS showing a sustained release over the 4‐week period in the CASS vs an initial burst release in the CSS. B, Release profile of azithromycin displaying sustained release over the 4‐week period in the CASS. Adapted from Reference 85. CASS, ciprofloxacin‐azithromycin sinus stent; CSS, ciprofloxacin sinus stent