{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:47:41Z","timestamp":1777538861390,"version":"3.51.4"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Solithromycin (CEM-101) is a \u201cfourth-generation\u201d macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug-resistant\n Streptococcus pneumoniae<\/jats:named-content>\n and nontypeable\n Haemophilus influenzae<\/jats:named-content>\n (NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains of\n S. pneumoniae<\/jats:named-content>\n or NTHi. Plasma PK (maximum concentration of drug in serum [\n C<\/jats:italic>\n max<\/jats:sub>\n ] and area under the concentration-time curve from 0 to 24 h [AUC\n 0\u201324<\/jats:sub>\n ]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg\/kg of body weight\/day resulted in\n C<\/jats:italic>\n max<\/jats:sub>\n and AUC\n 0\u201324<\/jats:sub>\n values of 2.2 \u03bcg\/ml and 27.4 \u03bcg \u00b7 h\/ml in plasma and 1.7 \u03bcg\/ml and 28.2 \u03bcg \u00b7 h\/ml in extracellular MEF on day 1. By day 3,\n C<\/jats:italic>\n max<\/jats:sub>\n and AUC\n 0\u201324<\/jats:sub>\n values had increased to 4.5 \u03bcg\/ml and 54 \u03bcg \u00b7 h\/ml in plasma and 4.8 \u03bcg\/ml and 98.6 \u03bcg \u00b7 h\/ml in extracellular MEF. For NTHi EOM, three isolates with MIC\/minimal bactericidal concentration (MBC) ratios of 0.5\/1 \u03bcg\/ml (isolate BCH1), 2\/2 \u03bcg\/ml (isolate BMC1247C), and 4\/4 \u03bcg\/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. For\n S. pneumoniae<\/jats:named-content>\n EOM, 3 isolates with MIC\/MBC ratios of 0.06\/0.125 \u03bcg\/ml (\n S. pneumoniae<\/jats:named-content>\n 331), 0.125\/1 \u03bcg\/ml (\n S. pneumoniae<\/jats:named-content>\n CP-645 [MLS\n B<\/jats:sub>\n phenotype]), and 0.5\/2 \u03bcg\/ml (CP-712 [\n mefA<\/jats:italic>\n subclass\n mefA<\/jats:italic>\n resistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected with\n S. pneumoniae<\/jats:named-content>\n 331 and\n S. pneumoniae<\/jats:named-content>\n CP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of \u22642 \u03bcg\/ml and 100% of ME infected with\n S. pneumoniae<\/jats:named-content>\n with an MIC of \u22640.125 \u03bcg\/ml.\n <\/jats:p>","DOI":"10.1128\/aac.00863-16","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T06:28:56Z","timestamp":1468304936000},"page":"5533-5538","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae"],"prefix":"10.1128","volume":"60","author":[{"given":"M.","family":"Figueira","sequence":"first","affiliation":[{"name":"Section of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Cempra, Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. I.","family":"Pelton","sequence":"additional","affiliation":[{"name":"Section of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912254"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.5311"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/11538720-S0-000000000-00002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04568-14"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01123-09"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2009.10.013"},{"key":"e_1_3_2_8_2","volume-title":"M100-S24 performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement","author":"CLSI","year":"2014","unstructured":"CLSI. 2014. M100-S24 performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. CLSI, Wayne, PA. http:\/\/microbiolab-bg.com\/wp-content\/uploads\/2015\/05\/CLSI-2014.pdf."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555817381.ch71"},{"key":"e_1_3_2_10_2","unstructured":"NCCLS. 1999. Methods for determining bactericidal activity of antimicrobial agents. NCCLS document M26-A. NCCLS Wayne PA. http:\/\/clsi.org\/."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.827-829.2005"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.05395-11"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01148-08"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.3.654-657.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01429-10"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-23"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02316-12"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00766-12"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(16)00017-7"},{"key":"e_1_3_2_20_2","volume-title":"Abstr Intersci Conf Antimicrob Agents Chemother (ICAAC)","author":"Hardy D","year":"2015","unstructured":"Hardy D, Pelton SI, Figueira M, Keedy K, Fernandes P, Vicino D. 2015. MICs and MBCs of solithromycin for nontypeable and typeable Haemophilus influenzae, abstr D-187. Abstr Intersci Conf Antimicrob Agents Chemother (ICAAC), San Diego, CA, 2015."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.200733"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02561-15"},{"key":"e_1_3_2_23_2","volume-title":"Abstr Pediatr Acad Soc Annu Meet","author":"Gonzalez D","year":"2015","unstructured":"Gonzalez D, Palazzi D, Bhattacharya-Mithal L, Al-Uzri A, James L, Bradley J, Neu N, Jasion T, Benjamin DK, Jr, Rosiak C, Oh R, Keedy K, Fernandes P, Cohen-Wolkowiez M. 2015. Pharmacokinetics and safety of solithromycin in adolescents with suspected or confirmed bacterial infection, abstr E-PAS2015:1545.340. Abstr Pediatr Acad Soc Annu Meet, San Diego, CA, 2015."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00863-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00863-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:28:59Z","timestamp":1645475339000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00863-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1128\/AAC.00863-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.00863-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"2016-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}