{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:15:22Z","timestamp":1781104522854,"version":"3.54.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Delayed eardrum healing has been observed in the ear opposite to the ear treated with otic quinolones (OQ) in rats. Case reports describe tendinopathies after OQ treatment, suggesting adverse systemic effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied patients aged 19 to 64 years with diagnosis of otitis externa or media in private insurance between 2005 and 2015. We compared OQ treatment against otic neomycin, oral amoxicillin, or azithromycin. Outcomes included Achilles tendon rupture (ATR), Achilles tendinitis (AT), and all-type tendon rupture (ATTR). We applied an active comparator, new-user design with 1-year look-back and ceased follow-up at initiation of systemic steroids or oral quinolones, external injury, hospitalization, and after 35 days. We used trimmed stabilized inverse probability of treatment weights to balance comparison groups in a survival framework. Negative outcomes (clavicle fractures or sports injuries) were examined to rule out differences from varied physical activity (unmeasured confounding).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We examined 1 501 009 treated otitis episodes. Hazard ratios (HR) for OQ exposure associated with ATR were 4.49 (95% confidence interval [CI], 1.83\u201311.02), AT 1.04 (95% CI, 0.73\u20131.50), and ATTR 1.71 (95% CI, 1.21\u20132.41). Weighted risk differences (RD) per 100 000 episodes for OQ exposure were ATR 7.80 (95% CI, 0.72\u201314.89), AT 1.01 (95% CI, \u221212.80 to 14.81), and ATTR 18.57 (95% CI, 3.60\u201333.53). Corresponding HRs for clavicle fractures and sports injuries were HR,1.71 (95% CI, 0.55\u20135.27) and HR,1.45 (95% CI, 0.64\u20133.30), suggesting limited residual confounding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>OQ exposure may lead to systemic consequences. Clinicians should consider this potential risk and counsel patients accordingly. Risk factors and mechanisms for this rare, adverse effect deserve further evaluation. Mechanistic and other clinical studies are warranted to corroborate this finding.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac709","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T08:09:24Z","timestamp":1662451764000},"page":"e1360-e1368","source":"Crossref","is-referenced-by-count":7,"title":["Quinolone Ear Drops and Achilles Tendon Rupture"],"prefix":"10.1093","volume":"76","author":[{"given":"Phuong T","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida , Gainesville, Florida , USA"},{"name":"Faculty of Pharmacy, HUTECH University , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J","family":"Antonelli","sequence":"additional","affiliation":[{"name":"College of Public Health and Health Professions and College of Medicine, University of Florida , Gainesville, Florida , USA"},{"name":"Department of Otolaryngology, College of Medicine, University of Florida , Gainesville, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-5961","authenticated-orcid":false,"given":"Almut G","family":"Winterstein","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida , Gainesville, Florida , USA"},{"name":"College of Public Health and Health Professions and College of Medicine, University of Florida , Gainesville, Florida , USA"},{"name":"Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida , Gainesville, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"2023020817092777000_ciac709-B1","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s00228-019-02713-1","article-title":"Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis","volume":"75","author":"Alves","year":"2019","journal-title":"Eur J Clin Pharmacol"},{"key":"2023020817092777000_ciac709-B2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.annepidem.2013.12.009","article-title":"Peripheral neuropathy and Guillain\u2013Barr\u00e9 syndrome risks associated with exposure to systemic fluoroquinolones: a pharmacovigilance analysis","volume":"24","author":"Ali","year":"2014","journal-title":"Ann Epidemiol"},{"key":"2023020817092777000_ciac709-B3","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s40264-019-00828-z","article-title":"Fluoroquinolone use and the risk of collagen-associated adverse events: a systematic review and meta-analysis","volume":"42","author":"Yu","year":"2019","journal-title":"Drug Saf"},{"key":"2023020817092777000_ciac709-B4","doi-asserted-by":"crossref","first-page":"8023935","DOI":"10.1155\/2017\/8023935","article-title":"Treatment of the fluoroquinolone-associated disability: the pathobiochemical implications","volume":"2017","author":"Michalak","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"2023020817092777000_ciac709-B5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1871525717666190402121958","article-title":"Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: a systematic review and meta-analysis","volume":"17","author":"Rawla","year":"2019","journal-title":"Cardiovasc Hematol Agents Med Chem"},{"key":"2023020817092777000_ciac709-B6","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1001\/jamainternmed.2020.4192","article-title":"Association of infections and use of fluoroquinolones with the risk of aortic aneurysm or aortic dissection","volume":"180","author":"Dong","year":"2020","journal-title":"JAMA Intern Med"},{"key":"2023020817092777000_ciac709-B7","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1001\/jamainternmed.2020.4199","article-title":"Association of fluoroquinolones with the risk of aortic aneurysm or aortic dissection","volume":"180","author":"Gopalakrishnan","year":"2020","journal-title":"JAMA Intern Med"},{"key":"2023020817092777000_ciac709-B8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jbspin.2014.03.022","article-title":"Drug-induced tendinopathy: from physiology to clinical applications","volume":"81","author":"Kirchgesner","year":"2014","journal-title":"Joint Bone Spine"},{"key":"2023020817092777000_ciac709-B9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1177\/0194599819889607","article-title":"Appropriateness of otic quinolone use among privately insured US patients","volume":"162","author":"Tran","year":"2020","journal-title":"Otolaryngol-Head Neck Surg"},{"key":"2023020817092777000_ciac709-B10","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2016-2706","article-title":"Committee on Infectious Diseases. 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