e1-12: Alternative Medications in Tuberculosis Treatment

The medications listed alphabetically below are usually considered only in cases of drug resistance (clinical or laboratory) to first-line medications.

Capreomycin is an injectable agent given intramuscularly in doses of 15–20 mg/kg/day (maximal dose 1 g). Major toxicities include ototoxicity (both vestibular and cochlear) and nephrotoxicity. If the medication must be used in older patients, the dose should not exceed 750 mg.

Clofazimine is a phenazine dye used in the treatment of leprosy and is active in vitro against M avium complex and Mycobacterium tuberculosis. It is given orally as a single daily dose of 100 mg for treatment of M avium complex disease. With limited clinical efficacy data, its use for the therapy of tuberculosis is reserved for multidrug-resistant M tuberculosis. Adverse effects include nausea, vomiting, abdominal pain, and skin discoloration.

Cycloserine, a bacteriostatic agent, is given in doses of 10–15 mg/kg (not to exceed 1 g) orally and has been used in re-treatment regimens and for primary therapy of highly resistant M tuberculosis. It can induce a variety of central nervous system dysfunctions and psychotic reactions.

Ethionamide, like cycloserine, is bacteriostatic and is given orally in a dose of 15–20 mg/kg/day (maximal dose 1 g). It has been used in combination therapy but is poorly tolerated with marked gastric irritation.

The fluoroquinolones, particularly moxifloxacin, are active in vitro against M tuberculosis, with MICs of 0.25–2 mcg/mL. These medications have been demonstrated to be efficacious in treating tuberculosis in patients unable to take isoniazid, rifampin, and pyrazinamide; however, rapid emergence of resistance has been described. The combination of 6 months of the long-acting rifamycin, rifapentine, in combination with moxifloxacin, is as effective as standard therapy in the treatment of tuberculosis.

Linezolid is effective in achieving culture conversion in patients with treatment-refractory, highly resistant pulmonary tuberculosis. However, the long-term use of this agent for tuberculosis is associated with significant side effects, particularly at doses of 600 mg daily.