Ethambutol: An overview
- Richard H Drew, PharmD, MS, FCCP
Richard H Drew, PharmD, MS, FCCP
- Professor, Campbell University College of Pharmacy and Health Sciences
- Associate Professor and Clinical Pharmacist, Infectious Diseases
- Duke University Medical Center
Ethambutol is an antimycobacterial agent that is most commonly used in combination with other drugs in the treatment of tuberculosis . 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) .
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.
MECHANISM OF ACTION
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 .
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- 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.
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- American Thoracic Society, CDC, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003; 52:1.
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- 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.
- Leibold JE. The ocular toxicity of ethambutol and its relation to dose. Ann N Y Acad Sci 1966; 135:904.
- 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.
- 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.
- MECHANISM OF ACTION
- SPECTRUM OF ACTIVITY
- DOSING AND ADMINISTRATION
- SPECIAL POPULATIONS
- Liver failure
- Renal insufficiency
- Older adults
- HIV-infected patients
- ADVERSE REACTIONS
- Visual changes
- Other reactions
- DRUG INTERACTIONS
- SUMMARY AND RECOMMENDATIONS