Combination regimens ethambutol

The answer is c. (Hardman, pp 1161-1162.) An important problem in the chemotherapy of TB is bacterial drug resistance For this reason, concurrent administration of two or more drugs should be employed to delay the development of drug resistance. Isoniazid is often combined with ethambutol for this purpose. Streptomycin or rifampin may also be added to the regimen to delay even further the development of drug resistance. 

Quinolones are important recent additions to the therapeutic agents used against M. tuberculosis, especially in MDR strains. Clinical trials of ofloxacin in combination with isoniazid and rifampin have indicated activity comparable to that of ethambutol. In addition, quinolones, particularly ciprofloxacin, are used as part of a combined regimen in HIV-infected patients. 

Clarithromycin or azithromycin is recommended as first-line therapy for prophylaxis and treatment of disseminated infection caused by M. avium-intracellulare in AIDS patients and for treatment of pulmonary disease in non-HIV-infected patients. Azithromycin (1.2 g once weekly) or clarithromycin (500 mg twice daily) is recommended for primary prevention for AIDS patients with fewer than 50 CD cells per mm. Single-agent therapy should not be used for treatment of active disease or for secondary prevention in AIDS patients. Clarithromycin (500 mg twice daily) plus ethambutol (15 mg/kg once daily) with or without rifabutin is an effective combination regimen. Azithromycin (500 mg once daily) may be used instead of clarithromycin, but clarithromycin appears to be slightly more efficacious. Clarithromycin also has been used with minocychne for the treatment of Mycobacterium leprae in lepromatous leprosy. 

In some patients, the combination of antiretroviral agents may be so complex that the use of antituberculosis regimens containing no rifamycins may be considered. For such patients, a 9-month, largely intermittent, regimen consisting of isoniazid, streptomycin, pyrazinamide and ethambutol for 2 months then isoniazid, streptomycin, and pyrazinamide for 7 months is an option. 

A triple therapy regimen with combinations of clarithromycin or azithromycin plus ethambutol plus rifabutin is the current standard of care. However rifabutin may be omitted in HIV-infected patients on protease inhibitors because of significant interactions (Table 19). 

Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the five first-line agents for treatment of tuberculosis (Table 47-1). Isoniazid and rifampin are the two most active drugs. An isoniazid-rifampin combination administered for 9 months will cure 95-98% of cases of tuberculosis caused by susceptible strains. The addition of pyrazinamide to an isoniazid-rifampin combination for the first 2 months allows the total duration of therapy to be reduced to 6 months without loss of efficacy (Table 47-2). In practice, therapy is initiated with a four-drug regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin until susceptibility of the clinical isolate has been determined. Neither ethambutol nor streptomycin adds substantially to the overall activity of the regimen (ie, the duration of treatment cannot be further reduced if either drug is used), but they do provide additional coverage should the isolate prove to be resistant to isoniazid, rifampin, or both. Unfortunately, such resistance occurs in up to 10% of cases in the United States. Most patients with tuberculosis can be treated entirely as outpatients, with... 

Enhanced hepatotoxicity of conventional antituberculosis regimens has been reported in recipients of orthotopic hver transplants, which is not unexpected, because of bouts of organ rejection (25). The authors recommended ofloxacin for these patients on the basis of favorable outcome in six cases. A conventional antituberculosis induction regimen was used initially until hepatotoxicity developed in all six patients. Thereafter they were treated with a combination of ofloxacin and ethambutol, with apparent cure in all. It should be noted that most of the patients took isoniazid + rifampicin for almost 2 months, which is the usual period when hepatotoxic reactions occur. Perhaps one should evaluate substitution of rifampicin with ofloxacin from the very beginning in order to minimize hepatotoxicity, as well as interference with ciclosporin leading to graft rejection noted in an earlier study (26). 

M avium complex (MAC) is a cause of disseminated infections in AIDS patients. Currently, clarithromycin or azithromycin is recommended for prophylaxis in patients with CD4 counts less than 50/ xL. Treatment of MAC infections requires a combination of drugs, one favored regimen consisting of azithromycin or clarithromycin with ethambutol and rifabutin, a congener of rifampin. 

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