Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin is given twice weekly. Rifampin, 600 mg daily or twice weekly for 6 months, also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid for patients with latent tuberculosis who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain.
B. Other Indications
Rifampin has other uses in bacterial infections. An oral dosage of 600 mg twice daily for 2 days can eliminate meningococcal carriage. Rifampin, 20 mg/kg (maximum 600 mg) once daily for 4 days, is used as prophylaxis in contacts of children with Haemophilus influenzae type b disease. Rifampin combined with a second agent is sometimes used to eradicate staphylococcal carriage. Rifampin combination therapy is also used for treatment of serious staphylococcal infections such as osteomyelitis, prosthetic joint infections, and prosthetic valve endocarditis.
Rifampin imparts a harmless orange color to urine, sweat, and tears (soft contact lenses may be permanently stained). Occasional adverse effects include rashes, thrombocytopenia, and nephritis. Rifampin may cause cholestatic jaundice and occasionally hepatitis, and it commonly causes light-chain proteinuria. If administered less often than twice weekly, rifampin may cause a flu-like syndrome characterized by fever, chills, myalgias, anemia, and thrombocytopenia. Its use has been associated with acute tubular necrosis.
Ethambutol is a synthetic, water-soluble, heat-stable compound, the dextro-isomer of the structure shown below, dispensed as the dihydrochloride salt.
Mechanism of Action & Clinical Uses
Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene. Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1–5 mcg/mL.
Ethambutol is well absorbed from the gut. After ingestion of 25 mg/kg, a blood level peak of 2–5 mcg/mL is reached in 2–4 hours. About 20% of the drug is excreted in feces and 50% in urine in unchanged form. Ethambutol accumulates in renal failure, and the dose should be reduced to three times weekly if creatinine clearance is less than 30 mL/min. Ethambutol crosses the blood-brain barrier only when the meninges are inflamed. Concentrations in cerebrospinal fluid are highly variable, ranging from 4% to 64% of serum levels in the setting of meningeal inflammation.