Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.


D Byron May, PharmD, BCPS
Section Editor
David C Hooper, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline, doxycycline and minocycline), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad-spectrum antibacterial activity similar to the tetracyclines [1].

Doxycycline is one of the most active tetracyclines and is the most often used clinically since it possesses many advantages over traditional tetracycline and minocycline. Doxycycline can be administered twice daily, has both intravenous (IV) and oral (PO) formulations, achieves reasonable concentrations even if administered with food, and is less likely to cause photosensitivity [2]. Doxycycline may be an alternative for use in children since it binds calcium to a lesser extent than tetracycline, which can cause tooth discoloration and bony growth retardation. The increase in frequency of multidrug-resistant organisms has led to the resurgence of IV minocycline for the treatment of infections caused by these organisms [3].


The tetracyclines enter the bacterial cell wall in two ways: passive diffusion and an energy-dependent active transport system, which is probably mediated in a pH-dependent fashion. Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. Protein synthesis is ultimately inhibited, leading to a bacteriostatic effect [4].


In contrast to many other antibiotics, tetracyclines are infrequently inactivated biologically or altered chemically by resistant bacteria. Resistance to these agents develops primarily by preventing accumulation of the drug inside the cell either by decreasing influx or increasing efflux. Once resistance develops to one of the drugs in this class, it is typically conferred to all tetracyclines.

However, there are differences in resistance among species of bacteria. Resistance genes to tetracyclines often occur on plasmids or other transferable elements such as transposons [5]. Bacteria carrying a ribosome protection type of resistance gene produce a cytoplasmic protein that interacts with the ribosomes and allows the ribosomes to proceed with protein synthesis even in the presence of high intracellular levels of the drug [5,6].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Oct 16, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Stein GE, Craig WA. Tigecycline: a critical analysis. Clin Infect Dis 2006; 43:518.
  2. Perdue, BE, Standiford, HC. Tetracyclines. In: Antimicrobial Therapy and Vaccines, Yu, VL, Merigan, TC, Barriere, SL (Eds), Williams and Wilkins, Baltimore 1999. p.981.
  3. Colton B, McConeghy KW, Schreckenberger PC, Danziger LH. I.V. minocycline revisited for infections caused by multidrug-resistant organisms. Am J Health Syst Pharm 2016; 73:279.
  4. Schnappinger D, Hillen W. Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol 1996; 165:359.
  5. Speer BS, Shoemaker NB, Salyers AA. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev 1992; 5:387.
  6. Roberts MC. Tetracycline therapy: update. Clin Infect Dis 2003; 36:462.
  7. Tigecycline (tygacil). Med Lett Drugs Ther 2005; 47:73.
  8. Zhanel GG, Homenuik K, Nichol K, et al. The glycylcyclines: a comparative review with the tetracyclines. Drugs 2004; 64:63.
  9. Wyeth antibiotic Tygacil approved for broad-spectrum, early use. "The Pink Sheet" 2005; 67:12.
  10. Klein NC, Cunha BA. Tetracyclines. Med Clin North Am 1995; 79:789.
  11. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2006. Atlanta, GA: U.S. Department of Health and Human Services, November 2007.
  12. Centers for Disease Control and Prevention (CDC). Nonfatal, unintentional medication exposures among young children--United States, 2001-2003. MMWR Morb Mortal Wkly Rep 2006; 55:1.
  13. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26:1.
  14. Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet 1988; 15:355.
  15. Mandell, GL, Bennett, JE, Dolin, R, et al. Principles and Practices of Infectious Diseases, 6th ed, Churchill Livingstone, Philadelphia 2005.
  16. Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother 2006; 58:256.
  17. Yim CW, Flynn NM, Fitzgerald FT. Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis. Antimicrob Agents Chemother 1985; 28:347.
  18. MacGowan AP. Tigecycline pharmacokinetic/pharmacodynamic update. J Antimicrob Chemother 2008; 62 Suppl 1:i11.
  19. Heaton PC, Fenwick SR, Brewer DE. Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study. J Clin Pharm Ther 2007; 32:483.
  20. US Food and Drug Administration (FDA). FDA drug safety communication: Increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections . http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm (Accessed on September 02, 2010).
  21. US Food and Drug Administration (FDA). FDA drug safety communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new boxed warning. http://www.fda.gov/Drugs/DrugSafety/ucm369580.htm (Accessed on May 05, 2015).
  22. Pound MW, May DB. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther 2005; 30:291.
  23. Schlienger RG, Bircher AJ, Meier CR. Minocycline-induced lupus. A systematic review. Dermatology 2000; 200:223.
  24. Colmegna I, Perandones CE, Chaves JG. Minocycline induced lupus and autoimmune hepatitis. J Rheumatol 2000; 27:1567.
  25. Lawson TM, Amos N, Bulgen D, Williams BD. Minocycline-induced lupus: clinical features and response to rechallenge. Rheumatology (Oxford) 2001; 40:329.
  26. Christe C, Ricou F, Stoller R, Vogt N. Minocycline-induced pericardial effusion. Ann Pharmacother 2000; 34:875.