{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:23:17Z","timestamp":1791490997958,"version":"4.3.4"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Paratek Pharmaceuticals, Inc.","award":["62669"],"award-info":[{"award-number":["62669"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Limited oral antibiotic options exist for urinary tract infections (UTI) caused by ESBL-producing Enterobacterales. The aim of the study was to evaluate in vitro activity of omadacycline and comparator antibiotics against clinical ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae urinary isolates. 102 isolates each of E. coli and K. pneumoniae were collected from clinical urine specimens in 2019. By design, an equal number of each species were included that tested positive and negative for ESBL production. Omadacycline MICs were determined using gradient test strips and compared to MICs of comparator antibiotics as determined by an automated broth microdilution system. Isolates were considered susceptible to omadacycline if the MIC was \u22644 \u00b5g\/mL for each species. 54.9% of all ESBL-producing isolates were susceptible to omadacycline, but better susceptibility was observed for ESBL-producing E. coli (74.5%). Omadacycline MICs were 2\u20134 fold lower for E. coli and K. pneumoniae strains not producing ESBL. The omadacycline MIC 50 and 90 values were 4 and 16 \u00b5g\/mL, respectively, for all isolates studied. 74.5% of all isolates were considered susceptible to omadacycline. MICs were generally lower for E. coli strains with MIC 50 and 90 values of 4 and 8 \u00b5g\/mL, respectively (87.3% susceptible), compared with K. pneumoniae. Overall, the most active agents were omadacycline and nitrofurantoin, while other comparator antibiotics were less active. Omadacycline represents a promising oral antibiotic for treating UTI caused by ESBL-producing E. coli, particularly when resistance limits other oral options. Prospective, controlled clinical trials are needed to validate these in vitro results.<\/jats:p>","DOI":"10.3390\/antibiotics12060953","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T01:29:26Z","timestamp":1684891766000},"page":"953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro Activity of Omadacycline and Comparator Antibiotics against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Urinary Isolates"],"prefix":"10.3390","volume":"12","author":[{"given":"Tyler J.","family":"Stone","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Kilic","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3840-7143","authenticated-orcid":false,"given":"John C.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157, USA"},{"name":"Department of Internal Medicine, Section on Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Palavecino","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"k5092","DOI":"10.1136\/bmj.k5092","article-title":"Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study","volume":"364","author":"Chua","year":"2019","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijid.2019.11.009","article-title":"Indications and classes of outpatient antibiotic prescriptions in Japan: A descriptive study using the national database of electronic health insurance claims, 2012\u20132015","volume":"91","author":"Hashimoto","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1093\/cid\/ciq257","article-title":"International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases","volume":"52","author":"Gupta","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11845-012-0834-5","article-title":"An 11-year analysis of the prevalent uropathogens and the changing pattern of Escherichia coli antibiotic resistance in 38,530 community urinary tract infections, Dublin 1999\u20132009","volume":"182","author":"Cullen","year":"2013","journal-title":"Ir. J. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13756-021-00983-y","article-title":"Trends in prevalence of extended-spectrum beta-lactamase-producing Escherichia coli isolated from patients with community- and healthcare-associated bacteriuria: Results from 2014 to 2020 in an urban safety-net healthcare system","volume":"10","author":"Raphael","year":"2021","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa1914433","article-title":"Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012\u20132017","volume":"382","author":"Jernigan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jgar.2020.10.020","article-title":"Resistance among urinary tract pathogens collected in Europe during 2018","volume":"23","author":"Critchley","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1093\/cid\/ciab560","article-title":"Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: Rising ESBL strains and impact on patient management","volume":"73","author":"Kaye","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","unstructured":"World Health Organization (2023, May 04). Prioritization of Pathogens to Guide Discovery, Research and Development of New Antibiotics for Drug-Resistant Bacterial Infections, Including Tuberculosis. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-EMP-IAU-2017.12."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1128\/AAC.01242-13","article-title":"In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline","volume":"58","author":"Macone","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s40265-020-01257-4","article-title":"Omadacycline: A novel oral and intravenous aminomethylcycline antibiotic agent","volume":"80","author":"Zhanel","year":"2020","journal-title":"Drugs"},{"key":"ref_12","unstructured":"CLSI (2020). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [30th ed.]. CLSI supplement M100."},{"key":"ref_13","unstructured":"(2020, April 03). USFaDARasticfo, Available online: https:\/\/www.fda.gov\/drugs\/development-resources\/antibacterial-susceptibility-test-interpretive-criteria."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1086\/318850","article-title":"Urinary tract infections: Disease panorama and challenges","volume":"183","author":"Stamm","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s41182-020-00251-6","article-title":"Multidrug-resistant and extended-spectrum beta-lactamase-producing uropathogens in children in Bhaktapur, Nepal","volume":"48","author":"Raya","year":"2020","journal-title":"Trop. Med. Health"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Critchley, I.A., Cotroneo, N., Pucci, M.J., and Mendes, R. (2019). The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS ONE, 14.","DOI":"10.1101\/703199"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jmii.2010.08.012","article-title":"Antimicrobial susceptibilities of urinary extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin and nitrofurantoin in a teaching hospital in Taiwan","volume":"44","author":"Liu","year":"2011","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Overcash, J.S., Tzanis, E., Manley, A., Sirbu, A., Serio, A.W., White, T., Wright, K., Chitra, S., and Eckburg, P.B. (2020, January 21\u201325). Omadacycline in female adults with cystitis: Results from a randomized, double-blinded, adaptive phase 2 study. Proceedings of the ID Week 2020, Virtual Event.","DOI":"10.1093\/ofid\/ofaa439.1866"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Overcash, J.S., Tzanis, E., Manley, A., Sirbu, A., Serio, A.W., White, T., Wright, K., Chitra, S., and Eckburg, P.B. (2020, January 21\u201325). Omadacycline in female adults with acute pyelonephritis: Results from a randomized, double-blind, adaptive phase 2 study. Proceedings of the ID Week 2020, Virtual Event.","DOI":"10.1093\/ofid\/ofaa439.1865"},{"key":"ref_20","first-page":"2160","article-title":"In vitro activity of omadacycline and levofloxacin against Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus in human urine supplemented with calcium and magnesium","volume":"75","author":"Pagano","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jgar.2019.02.017","article-title":"Surveillance of omadacycline activity tested against clinical isolates from the United States and Europe: Results from the SENTRY Antimicrobial Surveillance Programme, 2017","volume":"19","author":"Huband","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xiao, M., Huang, J.J., Zhang, G., Yang, W.H., Kong, F., Kudinha, T., and Xu, Y.C. (2020). Antimicrobial activity of omadacycline in vitro against bacteria isolated from 2014 to 2017 in China, a multi-center study. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-02019-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.diagmicrobio.2018.01.019","article-title":"Activity of omadacycline tested against Enterobacteriaceae causing urinary tract infections from a global surveillance program (2014)","volume":"91","author":"Pfaller","year":"2018","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e02488-19","DOI":"10.1128\/AAC.02488-19","article-title":"Surveillance of omadacycline activity tested against clinical isolates from the United States and Europe: Report from the SENTRY Antimicrobial Surveillance Program, 2016 to 2018","volume":"64","author":"Pfaller","year":"2020","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/6\/953\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:43Z","timestamp":1760125243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/6\/953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["antibiotics12060953"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12060953","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]}}}