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

Ethambutol: An overview

Richard H Drew, PharmD, MS, FCCP, FIDP
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Ethambutol is an antimycobacterial agent that is most commonly used in combination with other drugs in the treatment of tuberculosis [1]. It is also used as part of a combination regimen in the therapy of Mycobacterium avium complex (MAC) infections in patients with or without concomitant infection with human immunodeficiency virus (HIV) [1].

The American Thoracic Society (ATS), United States Centers for Disease Control and Prevention (CDC), and Infectious Disease Society of America (IDSA) statement on the treatment of tuberculosis, as well as other ATS guidelines, can be accessed through the ATS website.


The mechanism of action of ethambutol is not completely known. There is evidence that the drug exerts its bacteriostatic activity by virtue of inhibition of arabinosyl transferase, an enzyme that polymerizes arabinose into arabinan and then arabinogalactan, a mycobacterial cell wall constituent.


Organisms with minimum inhibitory concentrations exceeding 5 mcg/mL are generally considered resistant to ethambutol. M. tuberculosis resistance to ethambutol is due to random spontaneous genetic mutations, occurring at a rate of approximately 1 in 107 organisms. Mutations most commonly result in increased production of the enzyme arabinosyl transferase, which overwhelms the inhibitory effects of ethambutol [2,3]. (See "Epidemiology and molecular mechanisms of drug-resistant tuberculosis".)

Primary (pretreatment) resistance rates of M. tuberculosis to ethambutol vary widely. Although a report from New York City cited primary resistance as high as 14 percent, a global survey performed in 35 countries between 1994 and 1997 found a primary ethambutol resistance rate of 1 percent [4].

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: Nov 07, 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. Lewis ML. Ethambutol. In: Antimicrobial Therapy and Vaccines, Yu V, Merigan T, Barriere S (Eds), Williams & Wilkins, Baltimore 1998.
  2. Telenti A, Philipp WJ, Sreevatsan S, et al. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med 1997; 3:567.
  3. Belanger AE, Besra GS, Ford ME, et al. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci U S A 1996; 93:11919.
  4. Pablos-Méndez A, Raviglione MC, Laszlo A, et al. Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med 1998; 338:1641.
  5. Karlson AG. The in vitro activity of ethambutol (dextro2,2[ethylenediimino]di-1-butanol) against tubercle bacilli and other microorganisms. Am Rev Resp Dis 1961; 83:905.
  6. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis 2016; 63:e147.
  7. Yang H, Enimil A, Gillani FS, et al. Evaluation of the Adequacy of the 2010 Revised World Health Organization Recommended Dosages of the First-line Antituberculosis Drugs for Children: Adequacy of Revised Dosages of TB Drugs for Children. Pediatr Infect Dis J 2018; 37:43.
  8. Chew R, Jongbloed S, Jegatheesan D, et al. Ethambutol Is Cleared by a Contemporary High-Flux Hemodialyzer, and Drug Monitoring Ensures Safety and Therapeutic Effect. Antimicrob Agents Chemother 2017; 61.
  9. Trébucq A. Should ethambutol be recommended for routine treatment of tuberculosis in children? A review of the literature. Int J Tuberc Lung Dis 1997; 1:12.
  10. Perlman DC, Segal Y, Rosenkranz S, et al. The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. Clin Infect Dis 2005; 41:1638.
  11. Leibold JE. The ocular toxicity of ethambutol and its relation to dose. Ann N Y Acad Sci 1966; 135:904.
  12. Griffith DE, Brown-Elliott BA, Shepherd S, et al. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2005; 172:250.
  13. Younossian AB, Rochat T, Ketterer JP, et al. High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis. Eur Respir J 2005; 26:462.