{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T08:55:43Z","timestamp":1786870543267,"version":"build-2736575974"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"19","funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"crossref","award":["NIHDC015050"],"award-info":[{"award-number":["NIHDC015050"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001680","name":"Charles H. Hood Foundation","doi-asserted-by":"crossref","award":["Child Health Research Award"],"award-info":[{"award-number":["Child Health Research Award"]}],"id":[{"id":"10.13039\/100001680","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006823","name":"Boston Children\u2019s Hospital","doi-asserted-by":"crossref","award":["Trailblazer Research Grant by the Department of Anesthesia"],"award-info":[{"award-number":["Trailblazer Research Grant by the Department of Anesthesia"]}],"id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008503","name":"Center for Integration of Medicine and Innovative Technology","doi-asserted-by":"crossref","award":["W81XWH-09-2-0001"],"award-info":[{"award-number":["W81XWH-09-2-0001"]}],"id":[{"id":"10.13039\/100008503","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,4]]},"abstract":"<jats:p>\n                    Otits media (OM) is the most frequent indication for antimicrobial prescription to US children.\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    (\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    ) remains one of the most common pathogens causing OM. Successful eradication of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    in the middle ear can be achieved by adhering to a 7\u201310 day regimen of oral antibiotics. However, oral drug administration is challenging for parents. Lack of adherence has been associated with treatment failure or early relapse. To overcome this challenge, we used a noninvasive formulation to achieve high transtympanic antibiotic flux and cured\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    OM in chinchillas. The formulation consists of a thermosensitive in situ gelling hydrogel, chemical permeation enhancers, and an antibiotic. The direct transport of drugs into the middle ear produced high concentrations of ciprofloxacin (in the range of hundreds of micrograms per milliliter) within the first 24 hours of administration. Drug concentrations above the minimum inhibitory concentration (MIC) for\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    were sustained throughout the 7-day treatment.\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    OM in a chinchilla model was successfully eradicated, without causing tissue toxicity. Transtympanic delivery minimized systemic drug exposure, as evidenced by undetectable levels in blood, measured by high-performance liquid chromatography.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.123415","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T11:01:24Z","timestamp":1538564484000},"source":"Crossref","is-referenced-by-count":38,"title":["Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by transtympanic delivery of antibiotics"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6427-026X","authenticated-orcid":true,"given":"Rong","family":"Yang","sequence":"first","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children\u2019s Hospital Boston, Harvard Medical School, Boston Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishakha","family":"Sabharwal","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadya","family":"Shlykova","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obiajulu S.","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children\u2019s Hospital Boston, Harvard Medical School, Boston Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I.","family":"Pelton","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Kohane","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children\u2019s Hospital Boston, Harvard Medical School, Boston Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-3488"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.113.5.1451"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506083322307"},{"issue":"137","key":"B4","first-page":"1","article-title":"Ambulatory health care visits by children: principal diagnosis and place of visit","author":"Freid","year":"1998","journal-title":"Vital Health Stat 13"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111732"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1542\/peds.99.3.e1"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmt066"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036226"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.154.4.395"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(05)70309-6"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq400"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.210"},{"issue":"Pt 1","key":"B13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1099\/jmm.0.45819-0","article-title":"Antimicrobial resistance in the nasopharyngeal flora of children with acute otitis media and otitis media recurring after amoxicillin therapy","volume":"54","author":"Brook","year":"2005","journal-title":"J Med Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2015.09.030"},{"key":"B15","unstructured":"About Antimicrobial Resistance. 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