{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:14:32Z","timestamp":1791576872417,"version":"4.3.4"},"reference-count":162,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use.<\/jats:p>","DOI":"10.3390\/biom14070783","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-4879","authenticated-orcid":false,"given":"Dimitris","family":"Kounatidis","sequence":"first","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-388X","authenticated-orcid":false,"given":"Maria","family":"Dalamaga","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Grivakou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-4042","authenticated-orcid":false,"given":"Irene","family":"Karampela","sequence":"additional","affiliation":[{"name":"Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Koufopoulos","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Dalopoulos","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Adamidis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Mylona","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Kaziani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-5393","authenticated-orcid":false,"given":"Natalia G.","family":"Vallianou","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1749-6632.2011.06354.x","article-title":"The history of the tetracyclines","volume":"1241","author":"Nelson","year":"2011","journal-title":"Ann. 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