Current recommendations state that bedaquiline, in combination with at least three other active medications, may be used for 24 weeks of treatment in adults with laboratory-confirmed pulmonary tuberculosis if the isolate is resistant to both isoniazid and rifampin. The recommended dosage for bedaquiline is 400 mg once daily orally for 2 weeks, followed by 200 mg three times a week for 22 weeks taken orally with food in order to maximize absorption. The most common adverse effects, occurring at rates of 25% or more, are nausea, arthralgia, and headache. Bedaquiline has been associated with both hepatotoxicity and cardiac toxicity. The FDA has issued a black-box warning related to the risk of QTc prolongation and associated mortality. It should be reserved for patients who do not have other treatment options and used with caution in patients with other risk factors for cardiac conduction abnormalities.
Many mycobacterial infections seen in clinical practice in the United States are caused by nontuberculous mycobacteria (NTM), formerly known as “atypical mycobacteria.” These organisms have distinctive laboratory characteristics, are present in the environment, and are generally not communicable from person to person. As a rule, these mycobacterial species are less susceptible than M tuberculosis to antituberculous drugs. On the other hand, agents
TABLE 47–3 Clinical features and treatment options for infections with atypical mycobacteria.
such as macrolides, sulfonamides, and tetracyclines, which are not active against M tuberculosis, may be effective for infections caused by NTM. Emergence of resistance during therapy is also a problem with these mycobacterial species, and active infection should be treated with combinations of drugs. M kansasii is susceptible to rifampin and ethambutol, partially susceptible to isoniazid, and completely resistant to pyrazinamide. A three-drug combination of isoniazid, rifampin, and ethambutol is the conventional treatment for M kansasii infection. A few representative pathogens, with the clinical presentation and the drugs to which they are often susceptible, are given in Table 47–3.
M avium complex (MAC), which includes both M avium and M intracellulare, is an important and common cause of disseminated disease in late stages of AIDS (CD4 counts < 50/μL). MAC is much less susceptible than M tuberculosis to most anti-tuberculous drugs. Combinations of agents are required to suppress the infection. Azithromycin, 500–600 mg once daily, or clarithromycin, 500 mg twice daily, plus ethambutol, 15 mg/kg/d, is an effective and well-tolerated regimen for treatment of disseminated disease. Some authorities recommend use of a third agent, especially rifabutin, 300 mg once daily. Other agents that may be useful are listed in Table 47–3. Azithromycin and clarithromycin are the prophylactic drugs of choice for preventing disseminated MAC in AIDS patients with CD4 cell counts less than 50/μL. Rifabutin in a single daily dose of 300 mg has been shown to reduce the incidence of MAC bacteremia but is less effective than macrolides.
Mycobacterium leprae has never been grown in vitro, but animal models, such as growth in injected mouse footpads, have permitted laboratory evaluation of drugs. Only those drugs with the widest clinical use are presented here. Because of increasing reports of dapsone resistance, treatment of leprosy with combinations of the drugs listed below is recommended.