{"doi":"10.1002/alr.23533","title":"Preclinical Therapeutic Efficacy of the Ciprofloxacin Azithromycin Sinus Stent for <i>Pseudomonas aeruginosa</i> Sinusitis","abstract":"Pseudomonas aeruginosa is frequently implicated in difficult-to-treat infectious cases due to its resistance to conventional antibiotics and ability to form biofilms [1, 2]. To avoid limitations of systemic antibiotic drug delivery, our previous studies explored the feasibility of a localized treatment approach using a novel ciprofloxacin and azithromycin sinus stent (CASS) to treat Pseudomonas sinusitis [3, 4]. It is double-layered, with an inner hydrophilic ciprofloxacin and an outer hydrophobic azithromycin. This double-layered coating technology prevents the burst release of the hydrophilic ciprofloxacin, allowing for prolonged local delivery. Our in vitro and in vivo findings were promising, demonstrating that CASS could deliver high local concentrations of antibiotics in the sinonasal epithelia without significant tissue inflammation or systemic side effects in a rabbit model [3, 4]. Preclinical stent trial appears to be a necessary step to determine preliminary efficacy before clinical trial [5]. This follow-up study aims to investigate the efficacy of the current generation CASS in a rabbit model of P. aeruginosa rhinosinusitis. The CASSs were fabricated as previously described [3]. This study received approval from the Institutional Animal Care and Use Committee at the University of Alabama Birmingham. 8 Pasteurella-free female New Zealand white rabbits (3–4 kg) underwent the following procedures with mild sedation without general anesthesia or inhalation anesthetic agents [3, 6, 7]. As explained previously, unilateral sinus outflows were occluded using a Merocel sponge (Medtronic Inc., FL) by placing in the middle meatus. Then, the left maxillary sinus was inoculated with 0.5 mL of P. aeruginosa (PA14) using a 25-gauge needle (4.0 × 108 colony forming units). At week 1, after removing the sponge, the stent (either Sham (n = 4) or CASS (n = 4)) was placed into the sinus as described previously through a hole in the roof of the sinus [3]. On the following days after stent placement, sinuses were irrigated with saline (1 mL) during the study period (× 3/week, a total of 6 irrigations) to simulate human saline irrigation [3]. The efficacy of CASS in treating P. aeruginosa rhinosinusitis in this model was evaluated over 2 weeks after the placement. At weeks 0, 1, and 3, rabbits underwent a computed tomography (CT) scan and a blood draw (heterophils, albumin). Rabbits were sacrificed in week 3 and epithelial/subepithelial thickness and inflammatory cell densities in the subepithelial layer were measured from the histology sections. All experiments were performed in triplicate. Statistical analysis was performed using GraphPad Prism 6.0 (La Jolla, CA) using Student's t-tests. Significance was set at p < 0.05. Radiographically, all rabbits demonstrated fulminant opacification of unilateral sinuses at week 1, which showed a successful infection with PA14. At week 3, Kerschner scale CT scores (% of opacification [8]) were lower in those CASS rabbits compared to the Sham, meaning statistical improvement of opacification with CASS (Sham = 8.74±0.62; CASS = 4.45±1.32, p = 0.041) (Figure 1A,B). At week 1, heterophil counts were significantly elevated in all rabbits (n = 8, p < 0.01) compared to baseline. With the restoration of mucociliary clearance (MCC: packing removal and sinus irrigation), heterophil counts were decreased by week 3 without a significant difference between the two groups (counts/mL, Sham = 2395±876, CASS = 1746±618, p > 0.05). Although CFUs from the CASS group were significantly lower than those from the Sham, statistical difference was lacking (p > 0.05) (see Supporting Information). There were no statistical differences in serum albumin levels between the groups at all time points (Weeks 0, 1, and 3) (p > 0.05). From histology sectioning, subepithelial heights were significantly different between the two groups (heights (µm), Sham = 137.6±3.7, CASS = 98.6±5.0, p < 0.005), even though there was no significant ","journal":"International Forum of Allergy & Rhinology","year":2025,"id":560394,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":416504,"name":"Dong‐Jin Lim","orcid":"0000-0002-1619-6648","position":1,"is_corresponding":false},{"id":1127808,"name":"Brenton T. Bicknell","orcid":"0009-0000-2101-2543","position":2,"is_corresponding":false},{"id":1101678,"name":"Daniel Skinner","orcid":"0000-0002-7401-7433","position":3,"is_corresponding":false},{"id":1101677,"name":"Shaoyan Zhang","orcid":"0000-0002-0188-5643","position":4,"is_corresponding":false},{"id":416507,"name":"Bradford A. Woodworth","orcid":"0000-0003-3292-9167","position":5,"is_corresponding":false},{"id":298600,"name":"Do‐Yeon Cho","orcid":"0000-0002-5173-8959","position":6,"is_corresponding":false},{"id":1462628,"name":"Adam J. Skelton","orcid":null,"position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39811887","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}