{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:11:45Z","timestamp":1791663105467,"version":"4.3.4"},"reference-count":190,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure. The first modern tetracycline introduced into therapy was tigecycline, followed by omadacycline, eravacycline, and sarecycline (the third generation). Structural and physicochemical key elements which led to the discovery of modern tetracyclines are approached. Thus, several chemical subgroups are distinguished, such as glycylcyclines, aminomethylcyclines, and fluorocyclines, which have excellent development potential. The antibacterial spectrum comprises several resistant bacteria, including those resistant to old tetracyclines. Sarecycline, a narrow-spectrum tetracycline, is notable for being very effective against Cutinebacterium acnes. The mechanism of antibacterial action from the perspective of the new compound is approached. Several severe bacterial infections are treated with tigecycline, omadacycline, and eravacycline (with parenteral or oral formulations). In addition, sarecycline is very useful in treating acne vulgaris. Tetracyclines also have other non-antibiotic properties that require in-depth studies, such as the anti-inflammatory effect effect of sarecycline. The main side effects of modern tetracyclines are described in accordance with published clinical studies. Undoubtedly, this class of antibiotics continues to arouse the interest of researchers. As a result, new derivatives are developed and studied primarily for the antibiotic effect and other biological effects.<\/jats:p>","DOI":"10.3390\/pharmaceutics13122085","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"2085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":196,"title":["The Development of Third-Generation Tetracycline Antibiotics and New Perspectives"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-6903","authenticated-orcid":false,"given":"Aura","family":"Rusu","sequence":"first","affiliation":[{"name":"Pharmaceutical and Therapeutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-6507","authenticated-orcid":false,"given":"Emanuela Lorena","family":"Buta","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Therapeutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,5]]},"reference":[{"key":"ref_1","unstructured":"Bennett, J.E., Dolin, R., and Blaser, M.J. (2015). 26\u2014Tetracyclines, Glycylcyclines, and Chloramphenicol. Mandell, Douglas, and Bennett\u2019s Principles and Practice of Infectious Diseases, W.B. Saunders. [8th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0025-7125(16)30039-6","article-title":"Tetracyclines","volume":"79","author":"Klein","year":"1995","journal-title":"Med. Clin. N. Am."},{"key":"ref_3","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. N. Y. Acad. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1749-6632.1948.tb27262.x","article-title":"Aureomycin; a product of the continuing search for new antibiotics","volume":"51","author":"Duggar","year":"1948","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1084\/jem.73.5.629","article-title":"The production of bactericidal substances by aerobic sporulating bacilli","volume":"73","author":"Dubos","year":"1941","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1749-6632.2010.05861.x","article-title":"Production of antibiotic substances by actinomycetes","volume":"1213","author":"Waksman","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/cpt19741513","article-title":"Twenty-fifth anniversary of the discovery of Aureomycin: The place of the tetracyclines in antimicrobial therapy","volume":"15","author":"Finland","year":"1974","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/163159a0","article-title":"Aureomycin, a New Antibiotic","volume":"163","author":"Raistrick","year":"1949","journal-title":"Nature"},{"key":"ref_9","unstructured":"The Tetracyclines, Hlavka, J.J., and Boothe, J.H. (1985). Handbook of Experimental Pharmacology, Springer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"C539","DOI":"10.1152\/ajpcell.00047.2010","article-title":"Tetracyclines: A pleitropic family of compounds with promising therapeutic properties. Review of the literature","volume":"299","author":"Griffin","year":"2010","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_11","first-page":"6","article-title":"A brief history of pfizer central research","volume":"25","author":"Lombardino","year":"2000","journal-title":"Bull. Hist. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4976","DOI":"10.1021\/ja01139a533","article-title":"Terramycin. VIII. structure of aureomycin and terramycin","volume":"74","author":"Stephens","year":"1952","journal-title":"J. Am. Chem. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2165\/00003495-200464010-00005","article-title":"The Glycylcyclines: A Comparative Review with the Tetracyclines","volume":"64","author":"Zhanel","year":"2004","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hlavka, J.J., and Boothe, J.H. (1985). Chemical Modification of the Tetracyclines. The Tetracyclines, Springer. Handbook of Experimental Pharmacology.","DOI":"10.1007\/978-3-642-70304-1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1021\/ja01573a089","article-title":"A new family of antibiotics: The demethyltetracyclines","volume":"79","author":"McCormick","year":"1957","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","unstructured":"(2021, October 29). NCATS Inxight Drugs\u2014Methacycline. Available online: https:\/\/drugs.ncats.io\/substance\/IR235I7C5P."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"a025387","DOI":"10.1101\/cshperspect.a025387","article-title":"Tetracycline Antibiotics and Resistance","volume":"6","author":"Grossman","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1007\/s10096-019-03590-3","article-title":"Eravacycline, a newly approved fluorocycline","volume":"38","author":"Lee","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.2217\/fmb-2019-0199","article-title":"Sarecycline: A narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris","volume":"14","author":"Moore","year":"2019","journal-title":"Futur. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fuoco, D. (2012). Classification Framework and Chemical Biology of Tetracycline-Structure-Based Drugs. Antibiotics, 1.","DOI":"10.3390\/antibiotics1010001"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.2217\/fmb-2016-0100","article-title":"Omadacycline: Development of a novel aminomethylcycline antibiotic for treating drug-resistant bacterial infections","volume":"11","author":"Villano","year":"2016","journal-title":"Futur. Microbiol."},{"key":"ref_23","unstructured":"Giovanni, P., Eugenio, C., Giuseppe, M., Brenner, M., Lu, R., Huang, S., Armstrong, W.P., Gajanan, J., Seyedi, F., and Johnston, S. (2021). Process for Making Sarecycline Hydrochloride. (17\/043,017), U.S. Patent."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40828-021-00138-x","article-title":"Tetracycline antibiotics","volume":"7","author":"Ramachanderan","year":"2021","journal-title":"ChemTexts"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.1021\/jo030047d","article-title":"Versatile and Facile Synthesis of Diverse Semisynthetic Tetracycline Derivatives via Pd-Catalyzed Reactions","volume":"68","author":"Nelson","year":"2003","journal-title":"J. Org. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.diagmicrobio.2012.12.004","article-title":"Tigecycline: An update","volume":"75","author":"Stein","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1515\/hsz-2013-0292","article-title":"Tetracycline antibiotics and resistance mechanisms","volume":"395","author":"Nguyen","year":"2014","journal-title":"Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.clinthera.2006.08.011","article-title":"Tigecycline: A glycylcycline antimicrobial agent","volume":"28","author":"Doan","year":"2006","journal-title":"Clin. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/08998280.2006.11928154","article-title":"Tigecycline (Tygacil): The First in the Glycylcycline Class of Antibiotics","volume":"19","author":"Greer","year":"2006","journal-title":"Bayl. Univ. Med. Cent. Proc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1128\/AAC.01499-05","article-title":"Functional, Biophysical, and Structural Bases for Antibacterial Activity of Tigecycline","volume":"50","author":"Olson","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","unstructured":"FDA (2021, October 04). Drug Approval Package: Tygacil (Tigecycline) NDA #021821, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2005\/21-821_Tygacil.cfm."},{"key":"ref_32","unstructured":"(2021, September 29). EMA Tygacil. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/tygacil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S354","DOI":"10.1086\/431676","article-title":"The Efficacy and Safety of Tigecycline for the Treatment of Complicated Intra-Abdominal Infections: Analysis of Pooled Clinical Trial Data","volume":"41","author":"Babinchak","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1128\/AAC.49.11.4658-4666.2005","article-title":"Safety and Efficacy of Tigecycline in Treatment of Skin and Skin Structure Infections: Results of a Double-Blind Phase 3 Comparison Study with Vancomycin-Aztreonam","volume":"49","author":"Breedt","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.diagmicrobio.2008.04.009","article-title":"Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia","volume":"61","author":"Tanaseanu","year":"2008","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1586\/eri.09.73","article-title":"Tigecycline for the treatment of patients with community-acquired pneumonia requiring hospitalization","volume":"7","author":"Falagas","year":"2009","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_37","unstructured":"(2021, August 02). Tigecycline|DrugBank Online. Available online: https:\/\/go.drugbank.com\/drugs\/DB00560."},{"key":"ref_38","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_39","unstructured":"(2021, October 04). FDA Drug Approval Package: Nuzyra, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/209816Orig1s000,209817Orig1s000TOC.cfm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s40265-016-0545-8","article-title":"Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent","volume":"76","author":"Zhanel","year":"2016","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40265-019-01067-3","article-title":"Eravacycline: A Review in Complicated Intra-Abdominal Infections","volume":"79","author":"Scott","year":"2019","journal-title":"Drugs"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bunick, C.G., Keri, J., Tanaka, S.K., Furey, N., Damiani, G., Johnson, J.L., and Grada, A. (2021). Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation. Antibiotics, 10.","DOI":"10.3390\/antibiotics10040439"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1177\/1060028019873111","article-title":"Sarecycline Review","volume":"54","author":"Haidari","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s40265-019-1053-4","article-title":"Sarecycline: First Global Approval","volume":"79","author":"Deeks","year":"2019","journal-title":"Drugs"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1358\/dot.2019.55.10.3045040","article-title":"Sarecycline hydrochloride for the treatment of acne vulgaris","volume":"55","author":"Kaul","year":"2019","journal-title":"Drugs Today"},{"key":"ref_46","unstructured":"FDA (2021, October 07). Drug Approval Package: Seysara (Sarecycline), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/209521Orig1s000TOC.cfm."},{"key":"ref_47","unstructured":"Syst\u00e8mes, D. (2021, July 06). BIOVIA Draw for Academics. Available online: https:\/\/discover.3ds.com\/biovia-draw-academic."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2174\/138955712798868977","article-title":"Tetracyclines: Drugs with Huge Therapeutic Potential","volume":"12","author":"Bahrami","year":"2012","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_49","first-page":"001","article-title":"Tetracycline: Classification, Structure Activity Relationship and Mechanism of Action as a Theranostic Agent for Infectious Lesions-A Mini Review","volume":"7","author":"Rizvi","year":"2018","journal-title":"Biomed. J. Sci. Tech. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10870-013-0407-0","article-title":"X-Ray Crystallography of Tetracycline, Doxycycline and Sancycline","volume":"43","author":"Heinemann","year":"2013","journal-title":"J. Chem. Crystallogr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7044","DOI":"10.1128\/AAC.01536-15","article-title":"Structure-Activity Relationship of the Aminomethylcyclines and the Discovery of Omadacycline","volume":"59","author":"Honeyman","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1586\/14787210.4.1.9","article-title":"Tigecycline: A novel glycylcycline antibiotic","volume":"4","author":"Zhanel","year":"2006","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_53","unstructured":"(2021, October 07). Omadacycline. Available online: https:\/\/go.drugbank.com\/drugs\/DB12455."},{"key":"ref_54","unstructured":"(2021, October 05). PubChem Omadacycline, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/54697325."},{"key":"ref_55","unstructured":"(2021, August 03). European Medicines Agency Xerava. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/xerava."},{"key":"ref_56","unstructured":"(2021, October 04). PubChem Sarecycline, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/54681908."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20530","DOI":"10.1073\/pnas.2008671117","article-title":"Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome","volume":"117","author":"Batool","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","unstructured":"John, M., and Beale, J.H.B. (2011). Wilson and Giswold\u2019s Organic Medicinal and Pharmaceutical Chemistry, Lippincott Williams & Wilkins, Wolters Kluwer Health. [12th ed.]."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121807","DOI":"10.1016\/j.jchromb.2019.121807","article-title":"Challenges in the bioanalysis of tetracyclines: Epimerisation and chelation with metals","volume":"1134\u20131135","author":"Bayliss","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envpol.2016.12.017","article-title":"Tetracyclines metal complexation: Significance and fate of mutual existence in the environment","volume":"221","author":"Pulicharla","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_61","first-page":"939","article-title":"Determination of Protonation Constants of Some Tetracycline Antibiotics by Potentiometry and Lc Methods in Water and Acetonitrile-Water Binary Mixtures","volume":"20","author":"Sanli","year":"2009","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s10646-011-0665-6","article-title":"Tetracycline adsorption on kaolinite: pH, metal cations and humic acid effects","volume":"20","author":"Zhao","year":"2011","journal-title":"Ecotoxicology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1524\/zpch.2006.220.4.441","article-title":"Novel Insight into the Protonation\u2013Deprotonation Equilibria of Tetracycline, Sancycline and 10-Propoxy-Sancycline in Aqueous Solution. I. Analysis of the pH-Dependent UV\/vis Absorption Spectra by the SVD Technique","volume":"220","author":"Schmitt","year":"2006","journal-title":"Z. Phys. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bpc.2007.04.005","article-title":"Ca2+ and Mg2+ bind tetracycline with distinct stoichiometries and linked deprotonation","volume":"128","author":"Jin","year":"2007","journal-title":"Biophys. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ica.2015.10.037","article-title":"Minocycline and tigecycline form higher-order Ca2+ complexes of stronger affinity than tetracycline","volume":"441","author":"Arias","year":"2016","journal-title":"Inorg. Chim. Acta"},{"key":"ref_66","unstructured":"(2021, October 11). Marvin|ChemAxon. Available online: https:\/\/chemaxon.com\/products\/marvin."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijms.2018.09.025","article-title":"Dissociative protonation and long-range proton migration: The chemistry of singly- and doubly-protonated tigecycline","volume":"434","author":"Tu","year":"2018","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1128\/AAC.44.3.763-766.2000","article-title":"Iron-Chelating Activity of Tetracyclines and Its Impact on the Susceptibility of Actinobacillus actinomycetemcomitans to These Antibiotics","volume":"44","author":"Grenier","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ccr.2016.04.009","article-title":"Impact of metal coordination on the antibiotic and non-antibiotic activities of tetracycline-based drugs","volume":"327\u2013328","author":"Guerra","year":"2016","journal-title":"Coord. Chem. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1590\/S0100-40422011000100022","article-title":"Coordena\u00e7\u00e3o de metais a antibi\u00f3ticos como uma estrat\u00e9gia de combate \u00e0 resist\u00eancia bacteriana","volume":"34","author":"Rocha","year":"2011","journal-title":"Qu\u00edm. Nova"},{"key":"ref_71","unstructured":"Beale, J.M., and Block, J.H. (2010). Wilson and Gisvold\u2019s Textbook of Organic Medicinal and Pharmaceutical Chemistry, Wolters Kluwer Health. [12th ed.]."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0960-894X(99)00216-4","article-title":"Synthesis and structure-activity relationship of novel glycylcycline derivatives leading to the discovery of GAR-936","volume":"9","author":"Sum","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1517\/14740338.2015.997206","article-title":"Tigecycline: A critical safety review","volume":"14","author":"Kaewpoowat","year":"2014","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1073\/pnas.1216691110","article-title":"Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis","volume":"110","author":"Jenner","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance","volume":"65","author":"Chopra","year":"2001","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.2174\/0929867013371653","article-title":"Quinolone, Everninomycin, Glycylcycline, Carbapenem, Lipopeptide and Cephem Antibacterials in Clinical Development","volume":"8","author":"Bronson","year":"2001","journal-title":"Curr. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1016\/j.bmc.2016.07.029","article-title":"Discovery, pharmacology, and clinical profile of omadacycline, a novel aminomethylcycline antibiotic","volume":"24","author":"Tanaka","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.2147\/IDR.S171352","article-title":"Omadacycline: A novel aminomethylcycline","volume":"12","author":"Burgos","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1021\/jm201465w","article-title":"Fluorocyclines. 1. 7-Fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: A Potent, Broad Spectrum Antibacterial Agent","volume":"55","author":"Xiao","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1021\/jm201467r","article-title":"Fluorocyclines. 2. Optimization of the C-9 Side-Chain for Antibacterial Activity and Oral Efficacy","volume":"55","author":"Clark","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0092-8674(00)00216-6","article-title":"The Structural Basis for the Action of the Antibiotics Tetracycline, Pactamycin, and Hygromycin B on the 30S Ribosomal Subunit","volume":"103","author":"Brodersen","year":"2000","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0005-2787(67)90494-7","article-title":"Partial removal of bound transfer RNA from polysomes engaged in protein synthesis in vitro after addition of tetracycline","volume":"138","author":"Maxwell","year":"1967","journal-title":"Biochim. Biophys. Acta (BBA) Nucleic Acids Protein Synth."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1128\/AAC.01824-12","article-title":"Tigecycline DisplaysIn VivoBactericidal Activity against Extended-Spectrum-\u03b2-Lactamase-Producing Enterobacteriaceae after 72-Hour Exposure Period","volume":"57","author":"Tessier","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_84","unstructured":"(2021, September 30). BioRender. Available online: https:\/\/biorender.com\/."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00018-009-0172-6","article-title":"The tetracycline resistome","volume":"67","author":"Thaker","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s002030050339","article-title":"Tetracyclines: Antibiotic action, uptake, and resistance mechanisms","volume":"165","author":"Schnappinger","year":"1996","journal-title":"Arch. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.1016\/S0924-8579(09)70005-6","article-title":"A review of tigecycline\u2014The first glycylcycline","volume":"32","author":"Peterson","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/jac\/dki248","article-title":"Tigecycline","volume":"56","author":"Pankey","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"219S","DOI":"10.1592\/phco.20.14.219S.35046","article-title":"Preclinical Pharmacology of GAR-936, a Novel Glycylcycline Antibacterial Agent","volume":"20","author":"Projan","year":"2000","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1128\/AAC.48.6.2179-2184.2004","article-title":"Effects of Efflux Transporter Genes on Susceptibility of Escherichia coli to Tigecycline (GAR-936)","volume":"48","author":"Hirata","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1128\/AAC.01242-13","article-title":"In VitroandIn VivoAntibacterial Activities of Omadacycline, a Novel Aminomethylcycline","volume":"58","author":"Macone","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1177\/1060028019850173","article-title":"Eravacycline: The Tetracyclines Strike Back","volume":"53","author":"Heaney","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1128\/AAC.06187-11","article-title":"Target- and Resistance-Based Mechanistic Studies with TP-434, a Novel Fluorocycline Antibiotic","volume":"56","author":"Grossman","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/dth.12370","article-title":"The use of oral antibiotics in treating acne vulgaris: A new approach","volume":"29","author":"Farrah","year":"2016","journal-title":"Dermatol. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1529-8019.2012.01497.x","article-title":"New antibiotic therapies for acne and rosacea","volume":"25","author":"Mays","year":"2012","journal-title":"Dermatol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/ajd.12075","article-title":"Non-antibiotic properties of tetracyclines and their clinical application in dermatology","volume":"55","author":"Perret","year":"2013","journal-title":"Australas. J. Dermatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"426","DOI":"10.36849\/JDD.5923","article-title":"Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety","volume":"20","author":"Rosso","year":"2021","journal-title":"J. Drugs Dermatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jaad.2005.10.004","article-title":"Tetracyclines: Nonantibiotic properties and their clinical implications","volume":"54","author":"Sapadin","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1001\/archderm.1984.01650460048018","article-title":"Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy","volume":"120","author":"Esterly","year":"1984","journal-title":"Arch. Dermatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1001\/archderm.139.4.459","article-title":"Effects of Subantimicrobial-Dose Doxycycline in the Treatment of Moderate Acne","volume":"139","author":"Skidmore","year":"2003","journal-title":"Arch. Dermatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7326\/0003-4819-122-2-199501150-00001","article-title":"Minocycline in Rheumatoid Arthritis: A 48-Week, Double-Blind, Placebo-Controlled Trial","volume":"122","author":"Tilley","year":"1995","journal-title":"Ann. Intern. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/art.21620","article-title":"Treatment of early seropositive rheumatoid arthritis: Doxycycline plus methotrexate versus methotrexate alone","volume":"54","author":"Elliott","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1365-2133.1972.tb07416.x","article-title":"Perioral dermatitis: Aetiology and treatment with tetracycline","volume":"87","author":"Macdonald","year":"1972","journal-title":"Br. J. Dermatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1177\/014107689709000308","article-title":"Rosacea: Classification and Treatment","volume":"90","author":"Jansen","year":"1997","journal-title":"J. R. Soc. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/S0140-6736(05)79828-7","article-title":"Minocycline in early diffuse scleroderma","volume":"352","author":"Le","year":"1998","journal-title":"Lancet"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0738-081X(00)00187-5","article-title":"Tetracycline and niacinamide in the treatment of blistering skin diseases","volume":"19","author":"Chaidemenos","year":"2001","journal-title":"Clin. Dermatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/ijc.10168","article-title":"Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model","volume":"98","author":"Lokeshwar","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_108","first-page":"153","article-title":"Matrix Metalloproteinase Inhibitor COL-3 in the Treatment of AIDS-Related Kaposi\u2019s Sarcoma: A Phase I AIDS Malignancy Consortium Study","volume":"20","author":"Cianfrocca","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1067\/mva.2001.117891","article-title":"Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: A randomized, double-blind, placebo-controlled pilot study","volume":"34","author":"Mosorin","year":"2001","journal-title":"J. Vasc. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1001\/archderm.137.1.69","article-title":"The Use of Tetracyclines for the Treatment of Sarcoidosis","volume":"137","author":"Bachelez","year":"2001","journal-title":"Arch. Dermatol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/jac\/49.2.411","article-title":"Modulation of oxidative burst of neutrophils by doxycycline in patients with acute myocardial infarction","volume":"49","author":"Takeshita","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/09546638909086683","article-title":"The successful use of minocycline in pyoderma gangrenosum\u2014A report of seven cases and review of the literature","volume":"1","author":"Mrcp","year":"1989","journal-title":"J. Dermatol. Treat."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1034\/j.1600-051X.2001.280806.x","article-title":"Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A Comparative Multi-Centre Trial of 2 Treatment Approaches","volume":"28","author":"Newman","year":"2001","journal-title":"J. Clin. Periodontol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0190-9622(98)70272-5","article-title":"Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa","volume":"39","author":"Jemec","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/j.1365-2133.1993.tb00242.x","article-title":"Successful treatment of Sweet\u2019s syndrome with doxycycline","volume":"128","author":"Joshi","year":"1993","journal-title":"Br. J. Dermatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2340\/0001555571189194","article-title":"Use of anti-collagenase properties of doxycycline in treatment of alpha 1-antitrypsin deficiency panniculitis","volume":"71","author":"Humbert","year":"1991","journal-title":"Acta Derm. Venereol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2133.1974.tb12902.x","article-title":"Tetracycline for the treatment of pityriasis lichenoides","volume":"91","author":"Piamphongsant","year":"1974","journal-title":"Br. J. Dermatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/FTD.0b013e3181dda54f","article-title":"Tigecycline: A Review of Properties, Applications, and Analytical Methods","volume":"32","author":"Salgado","year":"2010","journal-title":"Ther. Drug Monit."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1128\/JCM.00637-08","article-title":"In Vitro Activity of Tigecycline against Gram-Positive and Gram-Negative Pathogens as Evaluated by Broth Microdilution and Etest","volume":"46","author":"Pillar","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"S303","DOI":"10.1086\/431672","article-title":"Tigecycline: A New Glycylcycline for Treatment of Serious Infections","volume":"41","author":"Noskin","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1128\/AAC.43.4.738","article-title":"In Vitro and In Vivo Antibacterial Activities of a Novel Glycylcycline, the 9- t -Butylglycylamido Derivative of Minocycline (GAR-936)","volume":"43","author":"Petersen","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1093\/cid\/ciz395","article-title":"Microbiology and Preclinical Review of Omadacycline","volume":"69","author":"Karlowsky","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e02411-16","DOI":"10.1128\/AAC.02411-16","article-title":"Activities of Omadacycline and Comparator Agents against Staphylococcus aureus Isolates from a Surveillance Program Conducted in North America and Europe","volume":"61","author":"Pfaller","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e02551-17","DOI":"10.1128\/AAC.02551-17","article-title":"Comparative In Vitro Activity of Omadacycline against Dog and Cat Bite Wound Isolates","volume":"62","author":"Goldstein","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","unstructured":"(2021, June 10). Antimicrobial Drugs Advisory Committee (AMDAC) Briefing Book. Omadacycline P-Toluenesulfonate Tablets and Injection, Available online: https:\/\/www.fda.gov\/media\/115100\/download."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e01297-18","DOI":"10.1128\/AAC.01297-18","article-title":"Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris","volume":"63","author":"Zhanel","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5021\/ad.2020.32.1.21","article-title":"Minocycline and Its Impact on Microbial Dysbiosis in the Skin and Gastrointestinal Tract of Acne Patients","volume":"32","author":"Thompson","year":"2020","journal-title":"Ann. Dermatol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Graber, E.M. (2021). Treating acne with the tetracycline class of antibiotics: A review. Dermatol. Rev., 1\u201310.","DOI":"10.1002\/der2.49"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S1471-4892(01)00081-9","article-title":"Glycylcyclines: Third-generation tetracycline antibiotics","volume":"1","author":"Chopra","year":"2001","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1128\/AAC.01066-13","article-title":"Mechanism of Action of the Novel Aminomethylcycline Antibiotic Omadacycline","volume":"58","author":"Draper","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s00239-007-9006-z","article-title":"Molecular Evidence for the Ancient Origin of the Ribosomal Protection Protein That Mediates Tetracycline Resistance in Bacteria","volume":"65","author":"Kobayashi","year":"2007","journal-title":"J. Mol. Evol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"52346","DOI":"10.1074\/jbc.M409573200","article-title":"TetX Is a Flavin-dependent Monooxygenase Conferring Resistance to Tetracycline Antibiotics","volume":"279","author":"Yang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1177\/1060028018818094","article-title":"Omadacycline: A New Tetracycline Antibiotic","volume":"53","author":"Dougherty","year":"2018","journal-title":"Ann. Pharmacother."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1128\/AAC.47.3.972-978.2003","article-title":"Efflux-Mediated Resistance to Tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1","volume":"47","author":"Dean","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/AAC.47.2.665-669.2003","article-title":"AcrAB Multidrug Efflux Pump Is Associated with Reduced Levels of Susceptibility to Tigecycline (GAR-936) in Proteus mirabilis","volume":"47","author":"Visalli","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1128\/AAC.01198-06","article-title":"Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii","volume":"51","author":"Peleg","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/AAC.00732-07","article-title":"AdeIJK, a Resistance-Nodulation-Cell Division Pump Effluxing Multiple Antibiotics in Acinetobacter baumannii","volume":"52","author":"Magnet","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1128\/AAC.49.5.1865-1871.2005","article-title":"A Novel MATE Family Efflux Pump Contributes to the Reduced Susceptibility of Laboratory-Derived Staphylococcus aureus Mutants to Tigecycline","volume":"49","author":"McAleese","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.1128\/AAC.00547-15","article-title":"The Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibility","volume":"59","author":"Beabout","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"11829","DOI":"10.1021\/bi0506066","article-title":"Tigecycline Is Modified by the Flavin-Dependent Monooxygenase TetX","volume":"44","author":"Moore","year":"2005","journal-title":"Biochemistry"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/s41564-019-0445-2","article-title":"Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans","volume":"4","author":"He","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e01326-19","DOI":"10.1128\/AAC.01326-19","article-title":"Novel Plasmid-Mediated tet (X5) Gene Conferring Resistance to Tigecycline, Eravacycline, and Omadacycline in a Clinical Acinetobacter baumannii Isolate","volume":"64","author":"Wang","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.femsle.2005.02.034","article-title":"Update on acquired tetracycline resistance genes","volume":"245","author":"Roberts","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Heidrich, C.G., Mitova, S., Schedlbauer, A., Connell, S.R., Fucini, P., Steenbergen, J.N., and Berens, C. (2016). The Novel Aminomethylcycline Omadacycline Has High Specificity for the Primary Tetracycline-Binding Site on the Bacterial Ribosome. Antibiotics, 5.","DOI":"10.3390\/antibiotics5040032"},{"key":"ref_145","unstructured":"(2021, June 06). XERAVA (Eravacycline) for Injection, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/211109lbl.pdf."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/phar.2366","article-title":"Evaluation of Eravacycline: A Novel Fluorocycline","volume":"40","author":"Alosaimy","year":"2020","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1128\/AAC.04809-14","article-title":"Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City","volume":"59","author":"Abdallah","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Robertsen, H.L., and Musiol-Kroll, E.M. (2019). Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs. Antibiotics, 8.","DOI":"10.3390\/antibiotics8040157"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0149-2918(04)90070-7","article-title":"Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients","volume":"26","author":"Postier","year":"2004","journal-title":"Clin. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"565438","DOI":"10.3389\/fmicb.2020.565438","article-title":"The Transcriptomic Signature of Tigecycline in Acinetobacter baumannii","volume":"11","author":"Li","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., and Sousa, M.E. (2019). Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020063"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1056\/NEJMoa1800201","article-title":"Omadacycline for Community-Acquired Bacterial Pneumonia","volume":"380","author":"Stets","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1056\/NEJMoa1800170","article-title":"Omadacycline for Acute Bacterial Skin and Skin-Structure Infections","volume":"380","author":"Green","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2147\/CCID.S190473","article-title":"Sarecycline: A Review of Preclinical and Clinical Evidence","volume":"13","author":"Moore","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_155","first-page":"E53","article-title":"Safety and Tolerability of Sarecycline for the Treatment of Acne Vulgaris: Results from a Phase III, Multicenter, Open-Label Study and a Phase I Phototoxicity Study","volume":"12","author":"Pariser","year":"2019","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1128\/AAC.49.1.220-229.2005","article-title":"Pharmacokinetics of Tigecycline after Single and Multiple Doses in Healthy Subjects","volume":"49","author":"Muralidharan","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1007\/s40265-018-1015-2","article-title":"Omadacycline: First Global Approval","volume":"78","author":"Markham","year":"2018","journal-title":"Drugs"},{"key":"ref_158","unstructured":"(2021, November 30). FDA Drug Approval Package: XERAVA (Eravacycline), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/211109Orig1s000TOC.cfm."},{"key":"ref_159","unstructured":"Shutter, M.C., and Akhondi, H. (2021). Tetracycline. StatPearls, StatPearls Publishing."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e02083-18","DOI":"10.1128\/AAC.02083-18","article-title":"Pharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b Study","volume":"63","author":"Overcash","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"S573","DOI":"10.1093\/ofid\/ofy210.1632","article-title":"1976. Pooled Analysis of Safety Data from Phases 2 and 3 Clinical Trials Evaluating Eravacycline in Complicated Intra-Abdominal Infections","volume":"5","author":"Efimova","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1001\/jamainternmed.2018.3931","article-title":"Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015\u20132016","volume":"178","author":"Moore","year":"2018","journal-title":"JAMA Intern. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1128\/AAC.01614-13","article-title":"Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections","volume":"58","author":"Solomkin","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_164","first-page":"987","article-title":"Once-Daily Oral Sarecycline 1.5 mg\/kg\/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials","volume":"17","author":"Moore","year":"2018","journal-title":"J. Drugs Dermatol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jama.1963.03060130026008","article-title":"Hypoplasia and Intrinsic Staining of Enamel Following Tetracycline Therapy","volume":"185","author":"Witkop","year":"1963","journal-title":"JAMA"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1248\/bpb.35.967","article-title":"Adverse Event Profile of Tigecycline: Data Mining of the Public Version of the U.S. Food and Drug Administration Adverse Event Reporting System","volume":"35","author":"Kadoyama","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_167","first-page":"229","article-title":"Tigecycline-induced acute pancreatitis: About two cases and review of the literature","volume":"67","author":"Marot","year":"2012","journal-title":"Acta Clin. Belg."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e02057-17","DOI":"10.1128\/AAC.02057-17","article-title":"Pharmacokinetics and Safety of Omadacycline in Subjects with Impaired Renal Function","volume":"62","author":"Berg","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1128\/AAC.01576-12","article-title":"Tigecycline Does Not Prolong Corrected QT Intervals in Healthy Subjects","volume":"57","author":"McGovern","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1093\/jac\/dkr242","article-title":"Efficacy and safety of tigecycline: A systematic review and meta-analysis","volume":"66","author":"Yahav","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_171","unstructured":"(2021, October 22). FDA Drug Safety Communication: Increased Risk of Death with Tygacil (Tigecycline) Compared to Other Antibiotics Used to Treat Similar Infections, Available online: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-increased-risk-death-tygacil-tigecycline-compared-other-antibiotics."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1128\/AAC.01402-10","article-title":"Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease","volume":"55","author":"Cai","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1473-3099(11)70177-3","article-title":"Efficacy and safety of tigecycline for the treatment of infectious diseases: A meta-analysis","volume":"11","author":"Tasina","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/cid\/cis270","article-title":"Excess Deaths Associated with Tigecycline After Approval Based on Noninferiority Trials","volume":"54","author":"Prasad","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1093\/cid\/cis274","article-title":"Editorial Commentary: Asking the Right Questions: Morbidity, Mortality, and Measuring What\u2019s Important in Unbiased Evaluations of Antimicrobials","volume":"54","author":"Powers","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijantimicag.2009.01.015","article-title":"Tigecycline possibly underdosed for the treatment of pneumonia: A pharmacokinetic viewpoint","volume":"34","author":"Burkhardt","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_177","unstructured":"Briggs, G.G., Freeman, R.K., and Yaffe, S.J. (2011). Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, Lippincott Williams & Wilkins. [9th ed.]."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1592\/phco.28.7.895","article-title":"Evaluation of a Potential Tigecycline-Warfarin Drug Interac","volume":"28","author":"Zimmerman","year":"2008","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_179","first-page":"429","article-title":"Antibiotic and Oral Contraceptive Drug Interactions: Is There a Need for Concern?","volume":"10","author":"Zhanel","year":"1999","journal-title":"Can. J. Infect. Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/j.bmcl.2006.11.055","article-title":"Newer tetracycline derivatives: Synthesis, anti-HIV, antimycobacterial activities and inhibition of HIV-1 integrase","volume":"17","author":"Sriram","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4155\/fmc.12.181","article-title":"Medicinal potential of ciprofloxacin and its derivatives","volume":"5","author":"Castro","year":"2013","journal-title":"Futur. Med. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1021\/acs.jmedchem.5b00262","article-title":"Design, Synthesis, and Biological Evaluation of Hexacyclic Tetracyclines as Potent, Broad Spectrum Antibacterial Agents","volume":"58","author":"Sun","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_183","unstructured":"(2021, October 06). Tetraphase.  Pipeline. Available online: https:\/\/www.tphase.com\/products\/pipeline\/."},{"key":"ref_184","unstructured":"(2021, October 24). PubChem TP-271, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/54726193."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"e00004-17","DOI":"10.1128\/mSphere.00004-17","article-title":"Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens","volume":"2","author":"Grossman","year":"2017","journal-title":"mSphere"},{"key":"ref_186","unstructured":"Sun, C., Deng, Y., Hunt, D., Fyfe, C., Kerstein, K., and Xiao, X. (2017). TP-6076, A Fully Synthetic Tetracycline Antibacterial Agent, Is Highly Potent against a Broad Range of Pathogens, Including Carbapenem-Resistant Enterobacteriaceae, ASM Microbe."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cbpa.2016.03.011","article-title":"Development of a platform for the discovery and practical synthesis of new tetracycline antibiotics","volume":"32","author":"Liu","year":"2016","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_188","unstructured":"Grossman, T., Hunt, D., Iii, H.H., and Sutcliffe, J. (2010, January 12\u201315). TP-271, a Novel Oral Fluorocycline for Community-Acquired Respiratory and Biothreat Pathogens. Proceedings of the 50th Annual Interscience Conference of Antimicrobial Agents and Chemotherapy, Boston, MA, USA."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"105829","DOI":"10.1016\/j.ijantimicag.2019.10.010","article-title":"In vitro activity of the novel fluorocycline TP-6076 against carbapenem-resistant Acinetobacter baumannii","volume":"55","author":"Seifert","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_190","unstructured":"Tetraphase Pharmaceuticals, Inc. (2021, November 28). A Phase 1, Open-Label, Randomized, PK and Safety Study to Assess Bronchopulmonary Disposition of Intravenous TP-6076 in Healthy Men and Women; ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03691584."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/12\/2085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:53Z","timestamp":1760168393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/12\/2085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,5]]},"references-count":190,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["pharmaceutics13122085"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13122085","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,5]]}}}