{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:01:49Z","timestamp":1784804509933,"version":"3.55.0"},"reference-count":48,"publisher":"American Veterinary Medical Association (AVMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"s001\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To determine whether an enrofloxacin\u2013silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s002\">\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>6 healthy adult New Zealand White rabbits.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s003\">\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears\/treatment) and scanning electron microscopic (1 ear\/treatment) examination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s004\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Most hearing thresholds (11\/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to &gt; 95 dB (the upper test limit) in saline solution\u2013treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s005\">\n<jats:title>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.80.4.325","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T12:13:16Z","timestamp":1553775196000},"page":"325-334","source":"Crossref","is-referenced-by-count":4,"title":["Effects of an enrofloxacin\u2013silver sulfadiazine emulsion in the ears of rabbits with perforated tympanic membranes"],"prefix":"10.2460","volume":"80","author":[{"given":"Fiona L.","family":"Bateman","sequence":"first","affiliation":[{"name":"1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon G. M.","family":"Kirejczyk","sequence":"additional","affiliation":[{"name":"2Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina V.","family":"Stewart","sequence":"additional","affiliation":[{"name":"1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Cutler","sequence":"additional","affiliation":[{"name":"1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Quilling","sequence":"additional","affiliation":[{"name":"1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Howerth","sequence":"additional","affiliation":[{"name":"2Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Mayer","sequence":"additional","affiliation":[{"name":"1Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Vet Clin North Am Exot Anim Pract","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.cvex.2015.08.005","article-title":"Surgical management of ear diseases in rabbits","volume":"19","author":"Csomos","year":"2016"},{"key":"ref2","series-title":"Lab Anim Sci","first-page":"343","article-title":"Suppurative otitis media in the rabbit: prevalence, pathology and microbiology","volume":"27","author":"Flatt","year":"1977"},{"issue":"suppl 3","key":"ref3","series-title":"Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"S79","DOI":"10.1016\/j.otohns.2003.12.007","article-title":"Ototoxicity of ototopical antibiotic drops in humans","volume":"130","author":"Matz","year":"2004"},{"issue":"suppl 3","key":"ref4","series-title":"Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"S57","DOI":"10.1016\/j.otohns.2003.12.008","article-title":"Animal ototoxicity of topical antibiotics and the relevance to clinical treatment of human subjects","volume":"130","author":"Roland","year":"2004"},{"key":"ref5","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1288\/00005537-197608000-00009","article-title":"Detection of ototoxicity from drugs applied topically to the middle ear space","volume":"86","author":"Brummett","year":"1976"},{"key":"ref6","series-title":"Arch Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1001\/archotol.1995.01890010027006","article-title":"Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla","volume":"121","author":"Jakob","year":"1995"},{"key":"ref7","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/jsap.12711","article-title":"Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy","volume":"59","author":"Paterson","year":"2018"},{"key":"ref8","series-title":"Int J Pediatr Otorhinolaryngol","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1016\/j.ijporl.2008.08.018","article-title":"Evaluating the ototoxicity of topical piperacillin-tazobactam","volume":"72","author":"Jang","year":"2008"},{"key":"ref9","series-title":"Arch Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1001\/archoto.2008.559","article-title":"Auditory function after a prolonged course of ciprofloxacin-dexamethasone otic suspension in a murine model","volume":"135","author":"Kavanagh","year":"2009"},{"key":"ref10","series-title":"Clin Otolaryngol","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/j.1749-4486.2007.01532.x","article-title":"Evidence review and ENT-UK consensus report for the use of aminoglycoside-containing ear drops in the presence of an open middle ear","volume":"32","author":"Phillips","year":"2007"},{"key":"ref11","series-title":"Otol Neurotol","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/mao.0b013e318057792f","article-title":"Ototoxic effect of Burow solution applied to the guinea pig middle ear","volume":"28","author":"Serin","year":"2007"},{"key":"ref12","series-title":"J Laryngol Otol","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1017\/S0022215115002509","article-title":"Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones","volume":"130","author":"Harris","year":"2016"},{"key":"ref13","series-title":"Cochrane Database Syst Rev","first-page":"CD005608","article-title":"Systemic antibiotics versus topical treatments for chronically discharging ears with underlying eardrum perforations","volume":"25","author":"Macfadyen","year":"2006"},{"key":"ref14","series-title":"Trop Med Int Health","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/j.1365-3156.2004.01368.x","article-title":"Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial","volume":"10","author":"Macfadyen","year":"2005"},{"key":"ref15","series-title":"Semin Vet Med Surg (Small Anim)","first-page":"3","article-title":"Otitis externa and otitis media: diagnostic and medical aspects","volume":"8","author":"Bruyette","year":"1993"},{"key":"ref16","series-title":"Vet Clin North Am Small Anim Pract","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.cvsm.2003.10.009","article-title":"Medical therapy of otitis externa and otitis media","volume":"34","author":"Morris","year":"2004"},{"key":"ref17","series-title":"Audiol Neurootol","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1159\/000094601","article-title":"Normative auditory brainstem response data for hearing threshold in the rabbit","volume":"11","author":"Stieve","year":"2006"},{"key":"ref18","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1002\/lary.25080","article-title":"Assessment of ototoxicity of intratympanic administration of Auralgan in a chinchilla animal model","volume":"125","author":"Mujica-Mota","year":"2015"},{"key":"ref19","series-title":"Ear Hear","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1097\/01.aud.0000233864.32183.81","article-title":"Perilymph\/modiolar communication routes in the human cochlea","volume":"27","author":"Rask-Andersen","year":"2006"},{"key":"ref20","series-title":"Neuroreport","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1097\/00001756-199309150-00016","article-title":"Expression of alpha-actinin in the stereocilia of hair cells of the inner ear: immunohistochemical localization","volume":"4","author":"Zine","year":"1993"},{"key":"ref21","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1097\/00005537-200209000-00015","article-title":"Round window gentamicin absorption: an in vivo human model","volume":"112","author":"Becvarovski","year":"2002"},{"key":"ref22","series-title":"CMAJ","first-page":"1056","article-title":"Aminoglycoside eardrops and ototoxicity","volume":"156","author":"Helal","year":"1997"},{"key":"ref23","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1097\/00005537-199907000-00015","article-title":"Ototoxicity of topical gentamicin preparations","volume":"109","author":"Bath","year":"1999"},{"key":"ref24","series-title":"Clin Otolaryngol Allied Sci","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1046\/j.1365-2273.1998.00161.x","article-title":"Ototoxicity and topical eardrops","volume":"23","author":"Marais","year":"1998"},{"key":"ref25","series-title":"Cochrane Database Syst Rev","first-page":"CD004618","article-title":"Topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations","volume":"19","author":"Macfadyen","year":"2005"},{"key":"ref26","series-title":"Glob J Health Sci","first-page":"144","article-title":"Comparison of local and systemic ciprofloxacin ototoxicity in the treatment of chronic media otitis","volume":"6","author":"Samarei","year":"2014"},{"key":"ref27","series-title":"Arch Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1001\/archoto.2009.30","article-title":"Safety of ciprofloxacin and dexamethasone in the guinea pig middle ear","volume":"135","author":"Lemke","year":"2009"},{"key":"ref28","series-title":"Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","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"},{"key":"ref29","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/cpt.603","article-title":"Drug-induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies","volume":"101","author":"Lanvers-Kaminsky","year":"2017"},{"key":"ref30","series-title":"Antimicrob Agents Chemother","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1128\/AAC.33.6.797","article-title":"Aminoglycoside-induced hearing loss in humans","volume":"33","author":"Brummett","year":"1989"},{"key":"ref31","series-title":"J Clin Diagn Res","first-page":"2408","article-title":"Artefacts: a diagnostic dilemma\u2014a review","volume":"7","author":"Rastogi","year":"2013"},{"key":"ref32","series-title":"Pathologic basis of veterinary disease","first-page":"1223","article-title":"The ear","author":"Njaa","year":"2017"},{"key":"ref33","series-title":"Fundamentals of toxicologic pathology","first-page":"729","article-title":"Special senses\u2014ear","author":"Schafer","year":"2018"},{"key":"ref34","series-title":"Hear Res","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0378-5955(91)90034-7","article-title":"Scar formation after drug-induced cochlear insult","volume":"51","author":"Raphael","year":"1991"},{"key":"ref35","series-title":"The laboratory rabbit, guinea pig, hamster, and other rodents","first-page":"1017","article-title":"Models related to hearing loss","author":"Martin","year":"2012"},{"key":"ref36","series-title":"J Wound Care","doi-asserted-by":"publisher","first-page":"155","DOI":"10.12968\/jowc.2005.14.4.26762","article-title":"Silver absorption and antibacterial efficacy of silver dressings","volume":"14","author":"Lansdown","year":"2005"},{"key":"ref37","series-title":"J Eur Acad Dermatol Venereol","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/jdv.12785","article-title":"Allergic contact dermatitis to silver in a patient treated with silver sulphadiazine after a burn","volume":"30","author":"Garc\u00eda","year":"2016"},{"key":"ref38","series-title":"J Burn Care Res","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1097\/BCR.0b013e3181a28c9b","article-title":"The side effects of silver sulfadiazine","volume":"30","author":"Fuller","year":"2009"},{"key":"ref39","series-title":"J Am Acad Dermatol","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1067\/S0190-9622(02)61574-9","article-title":"Scar-localized argyria secondary to silver sulfadiazine cream","volume":"49","author":"Fisher","year":"2003"},{"key":"ref40","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1097\/00005537-200009000-00021","article-title":"Vestibular and cochlear ototoxicity of topical antiseptics assessed by evoked potentials","volume":"110","author":"Perez","year":"2000"},{"key":"ref41","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1002\/lary.24041","article-title":"Ototoxicity of olive oil in a chinchilla animal model","volume":"123","author":"Emami","year":"2013"},{"key":"ref42","series-title":"Int J Pediatr Otorhinolaryngol","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.ijporl.2012.01.018","article-title":"Ototoxicity of baby oil in a chinchilla animal model","volume":"76","author":"Al-Jarallah","year":"2012"},{"key":"ref43","series-title":"Laryngoscope","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1002\/lary.22385","article-title":"Assessment of the ototoxicity of almond oil in a chinchilla animal model","volume":"121","author":"Peleva","year":"2011"},{"key":"ref44","series-title":"Otolaryngol Head Neck Surg","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1177\/0194599811429255","article-title":"Ototoxicity of intratympanic docusate sodium and mineral oil in the guinea pig","volume":"146","author":"Nader","year":"2012"},{"key":"ref45","series-title":"Ann Otol Rhinol Laryngol Suppl","first-page":"42","article-title":"Toxicity of ototopical drugs: animal modeling","volume":"148","author":"Morizono","year":"1990"},{"key":"ref46","series-title":"Anatomy of the temporal bone with surgical implications","author":"Schuknecht","year":"1986"},{"key":"ref47","series-title":"Ann Otol Rhinol Laryngol Suppl","first-page":"38","article-title":"Workshop on Chronic Suppurative Otitis Media: Etiology and Management. August 29\u201330, 1985, Pittsburgh, Pennsylvania. Proceedings","volume":"131","author":"Brown","year":"1988"},{"key":"ref48","series-title":"Baytril Otic [package insert]","year":"2017"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/80\/4\/ajvr.80.4.325.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/80\/4\/ajvr.80.4.325.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/80\/4\/ajvr.80.4.325.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T20:41:45Z","timestamp":1696538505000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/80\/4\/ajvr.80.4.325.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":48,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.80.4.325","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4]]}}}