{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:41:43Z","timestamp":1788356503995,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Objective: The aim of this study is to develop and evaluate the antibacterial and anti-biofilm efficacy of ciprofloxacin-coated tympanostomy tubes (TTs) using a sustained-release varnish (SRV-CIPRO) and introduce a novel tympanic membrane model for preclinical evaluation. Study Design: This was an in vitro experimental study. Setting: This study was conducted in a biofilm research laboratory in an academic medical center. Methods: Sterile fluoroplastic TTs were coated with SRV-CIPRO or placebo varnish. A novel tympanic membrane (TM) model was developed using a layered agar\u2013plastic system. Antibacterial activity, biofilm inhibition, and bacterial viability were assessed through agar diffusion, MTT, ATP quantification, HR-SEM, and SD-CLSM. Results: SRV-CIPRO-coated TTs exhibited sustained antibacterial activity for up to 10 days. Compared to the placebo, SRV-CIPRO significantly inhibited biofilm formation, reduced metabolic activity, and decreased bacterial viability (p &lt; 0.05). Imaging confirmed fewer bacterial colonies on SRV-CIPRO TTs. The TM model allowed realistic testing of tube insertion and infection simulation. Conclusion: SRV-CIPRO-coated TTs offer sustained antibiotic delivery, potentially reducing postoperative otorrhea and biofilm-related complications. The TM model provides a platform for preclinical evaluation of middle ear devices.<\/jats:p>","DOI":"10.3390\/microorganisms13092039","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:27:44Z","timestamp":1756733264000},"page":"2039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ciprofloxacin-Coated Tympanostomy Tubes with Sustained-Release Varnish: A Novel Strategy to Combat Biofilm Formation by Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"13","author":[{"given":"Sari","family":"Risheq","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel"},{"name":"The Biofilm Research Laboratory, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Sancho","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel"},{"name":"The Biofilm Research Laboratory, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Friedman","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irith","family":"Gati","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Eliashar","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Steinberg","sequence":"additional","affiliation":[{"name":"The Biofilm Research Laboratory, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menachem","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00405-009-1131-4","article-title":"The point prevalence of otitis media with effusion among primary school children in Western Sicily","volume":"267","author":"Martines","year":"2010","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_2","first-page":"e68006","article-title":"Integrated health solutions: Addressing the co-occurrence of otitis media with effusion and early childhood caries in preschool children","volume":"16","author":"Hashim","year":"2024","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368504241265171","DOI":"10.1177\/00368504241265171","article-title":"Advance in the pathogenesis of otitis media with effusion induced by platelet-activating factor","volume":"107","author":"Liu","year":"2024","journal-title":"Sci. Prog."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Monasta, L., Ronfani, L., Marchetti, F., Montico, M., Brumatti, L.V., Bavcar, A., Grasso, D., Barbiero, C., Tamburlini, G., and Moormann, A.M. (2012). Burden of disease caused by otitis media: Systematic review and global estimates. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036226"},{"key":"ref_5","first-page":"S1","article-title":"Clinical practice guideline: Otitis media with effusion (update)","volume":"154","author":"Rosenfeld","year":"2016","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.anl.2022.12.004","article-title":"Clinical practice guidelines for the diagnosis and management of otitis media with effusion (OME) in children in Japan\u20142022 update","volume":"50","author":"Hidaka","year":"2023","journal-title":"Auris Nasus Larynx"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck Surgery, and American Academy of Pediatrics Subcommittee on Otitis Media with Effusion (2004). Otitis media with effusion. Pediatrics, 113, 1412\u20131429.","DOI":"10.1542\/peds.113.5.1412"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0030-6665(05)70140-7","article-title":"Tympanostomy tubes: Types, indications, techniques, and complications","volume":"32","author":"Morris","year":"1999","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1056\/NEJMoa2027278","article-title":"Tympanostomy tubes or medical management for recurrent acute otitis media","volume":"384","author":"Hoberman","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8S","DOI":"10.1177\/0145561320929885","article-title":"Tympanostomy tubes\u2014A visual guide for the young otolaryngologist","volume":"99","author":"Isaacson","year":"2020","journal-title":"Ear Nose Throat J."},{"key":"ref_11","unstructured":"Spaw, M., Agarwal, N., and Camacho, M. (2025, August 21). Tympanostomy tube insertion, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK565858\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1001\/archotol.126.5.585","article-title":"Impact of tympanostomy tubes on child quality of life","volume":"126","author":"Rosenfeld","year":"2000","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0165-5876(01)00552-3","article-title":"comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against post-tympanostomy otorrhea","volume":"61","author":"Morpeth","year":"2001","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/archotol.1995.01890080048009","article-title":"Topical ciprofloxacin for otorrhea after tympanostomy tube placement","volume":"121","author":"Force","year":"1995","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1177\/0194599811409862","article-title":"Ventilation tube treatment: A systematic review of the literature","volume":"145","author":"Groth","year":"2011","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1177\/000348949410300909","article-title":"Acute otorrhea: Bacteriology of a common complication of tympanostomy tubes","volume":"103","author":"Mandel","year":"1994","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1177\/0194599812468849","article-title":"Clinical practice guideline: Tympanostomy tubes in children","volume":"149","author":"Rosenfeld","year":"2013","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_18","first-page":"KC01","article-title":"Topical vs. combination ciprofloxacin in the management of discharging chronic suppurative otitis media","volume":"8","author":"Renukananda","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1097\/00005537-200312000-00011","article-title":"Topical ciprofloxacin\/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes","volume":"113","author":"Roland","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0385-8146(98)00022-4","article-title":"Timing for removal of tympanic ventilation tube in children","volume":"25","author":"Iwaki","year":"1998","journal-title":"Auris Nasus Larynx"},{"key":"ref_21","first-page":"38","article-title":"Prophylactic ciprofloxacin drops after tympanostomy tube insertion","volume":"25","author":"Nawasreh","year":"2004","journal-title":"Saudi Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/archotol.1992.01880040050009","article-title":"Ciprofloxacin: Use as a topical otic preparation","volume":"118","author":"Brownlee","year":"1992","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.otohns.2008.08.005","article-title":"Ototoxicity of topical ciprofloxacin\/dexamethasone otic suspension in a chinchilla animal model","volume":"139","author":"Daniel","year":"2008","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00405-009-1012-x","article-title":"The effect of topical ciprofloxacin and steroid-containing ear drops for chronic suppurative otitis media on the internal ear","volume":"267","author":"Kapusuz","year":"2010","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/17425247.2016.1213239","article-title":"Sustained-release drug delivery of antimicrobials in controlling of supragingival oral biofilms","volume":"14","author":"Steinberg","year":"2017","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Feldman, M., Shenderovich, J., Lavy, E., Friedman, M., and Steinberg, D. (2017). A sustained-release membrane of thiazolidinedione-8: Effect on formation of a Candida\/bacteria mixed biofilm on hydroxyapatite in a continuous flow model. Biomed. Res. Int., 2017.","DOI":"10.1155\/2017\/3510124"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/ajcp\/45.4_ts.493","article-title":"Antibiotic susceptibility testing by a standardized single disk method","volume":"45","author":"Bauer","year":"1966","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Funk, B., Kirmayer, D., Sahar-Heft, S., Gati, I., Friedman, M., and Steinberg, D. (2019). Efficacy and potential use of novel sustained release fillers as intracanal medicaments against Enterococcus faecalis biofilm in vitro. BMC Oral Health, 19.","DOI":"10.1186\/s12903-019-0879-1"},{"key":"ref_29","first-page":"19","article-title":"Use of the BacTiter-Glo\u2122 microbial cell viability assay to study bacterial attachment in biofilm formation","volume":"99","author":"Sule","year":"2008","journal-title":"Promega Notes"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Duanis-Assaf, D., Kenan, E., Sionov, R., Steinberg, D., and Shemesh, M. (2020). Proteolytic activity of Bacillus subtilis upon \u03ba-casein undermines its \u201ccaries-safe\u201d effect. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020221"},{"key":"ref_31","first-page":"CD001801","article-title":"Grommets (ventilation tubes) for hearing loss associated with otitis media with effusion in children","volume":"10","author":"Browning","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1177\/0885328218802103","article-title":"A newly designed tympanostomy stent with TiO2 coating to reduce Pseudomonas aeruginosa biofilm formation","volume":"33","author":"Joe","year":"2018","journal-title":"J. Biomater. Appl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijporl.2012.10.027","article-title":"Biofilm formation on coated silicone tympanostomy tubes","volume":"77","author":"Silva","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1067\/mhn.2000.107458","article-title":"In vitro resistance to bacterial biofilm formation on coated fluoroplastic tympanostomy tubes","volume":"123","author":"Berry","year":"2000","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Russomando, A.C., Sionov, R.V., Friedman, M., Gati, I., Eliashar, R., Steinberg, D., and Gross, M. (2021). Sinonasal stent coated with slow-release varnish of chlorhexidine has sustained protection against bacterial biofilm growth in the sinonasal cavity: An in vitro study. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111783"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10123-021-00205-w","article-title":"Sustained release varnish containing chlorhexidine for prevention of Streptococcus mutans biofilm formation on voice prosthesis surface: An in vitro study","volume":"25","author":"Gross","year":"2022","journal-title":"Int. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jo, E.R., Oh, J., and Cho, S.I. (2022). Inhibitory effect of thymol on tympanostomy tube biofilms of methicillin-resistant Staphylococcus aureus and ciprofloxacin-resistant Pseudomonas aeruginosa. Microorganisms, 10.","DOI":"10.3390\/microorganisms10091867"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109622","DOI":"10.1016\/j.ijporl.2019.109622","article-title":"In vitro inhibitory activity of N-acetylcysteine on tympanostomy tube biofilms from methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa","volume":"126","author":"Jun","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1017\/S0022215118000932","article-title":"Comparative efficacies of topical antiseptic eardrops against biofilms from methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa","volume":"132","author":"Youn","year":"2018","journal-title":"J. Laryngol. Otol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/2039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:36:39Z","timestamp":1760034999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/2039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,31]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["microorganisms13092039"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13092039","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,31]]}}}