Ethambutol

Ethambutol is a first-line antitubercular antibiotic used in the treatment of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis. It is typically given in combination with isoniazid, rifampin, and pyrazinamide as part of the initial intensive phase of therapy (the RIPE regimen). It may also be used in selected non-tuberculous mycobacterial infections, though its role is limited compared with other agents.

Mechanism of action: Ethambutol inhibits arabinosyl transferases involved in the synthesis of the mycobacterial cell wall, particularly the arabinan component of arabinogalactan. This impairs cell wall formation and is generally described as bacteriostatic against M. tuberculosis.

Pharmacokinetics and dosing: Ethambutol is well absorbed orally and distributes systemically. It is excreted largely unchanged by the kidneys, so dose adjustment is required in renal impairment. Peak concentrations occur within 2–4 hours after ingestion. In TB treatment, ethambutol is typically given for the first 2 months; if the organism is proven susceptible to all first-line drugs, ethambutol can be discontinued during the continuation phase.

Adverse effects: The most important toxicity is optic neuritis, which can cause decreased visual acuity and impaired red-green color discrimination. This risk increases with higher doses and with prolonged use; baseline and periodic ophthalmologic examinations are recommended. Other adverse effects are generally mild and can include hypersensitivity reactions and gastrointestinal upset.

Resistance and considerations: Resistance arises mainly from mutations in embB and related genes encoding arabinosyl transferases. Ethambutol should be avoided in patients with known optic neuritis. In pregnancy, use only if clearly indicated. Drug interactions are limited but should be considered with other antitubercular drugs.