Rifabutin Ethambutol

M avium complex Pulmonary disease in patients with chronic lung disease disseminated infection in AIDS Amikacin, azithromycin, clarithromycin, ciprofloxacin, ethambutol, rifabutin... 

Mycobacterium avium complex Involvement of bone marrow, reticuloendothelial tissues Clarithromycin plus ethambutol rifabutin... 

Benson CA, Williams PL, Currier IS, et al. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. CUn Infect Dis 2003 37 1234-1243. 

Clarilhromycin 500 mg orally twice daily, plus ethambutol 15 mg/kg/day orally (Al), and For advanced disease, rifabutin 300 rng/day (dose may need adjustment with ART) (Al) ... 

HIV - The initial phase of a 6-month tuberculosis regimen consists of isoniazid, rifabutin, pyrazinamide, and ethambutol for patients receiving therapy with protease inhibitors or nonnucleoside reverse transcriptase inhibitors. These drugs are administered a) daily for at least the first 2 weeks, followed by twice weekly dosing for 6 weeks or b) daily for 8 weeks to complete the 2-month induction phase. The second phase of treatment consists of rifabutin and isoniazid administered twice weekly or daily for 4 months. 

Among the antimycobacterials often a differentiation is made between first-choice and second-choice agents. The first-choice agents include iso-niazid, rifampicin, ethambutol, pyrazinamide and streptomycin or as alternatives the other aminoglycosides amikacine or kanamycine. The second-choice agents include the quinolones ciprofloxacin and ofloxacin and also the rifamycin derivative rifabutin. 

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). 

D. Sassela, and R. Rimoldi (1999). Effect of rifabutin on ethambutol pharmacokineticsa in healthy volunteers. Pharmacology Research 40 351-356. 

The drugs used to treat TB include capreomycin, cycloserine, ethambutol, isoniazid, pyrazinamide, rifabutin, rifampicin and streptomycin. Resistance is most likely with long courses of treatment of antimicrobial agents and treatment courses are six (or even nine) months long. 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Shafran SD, Deschenes J, Miller M, Phillips P, Toma E. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. MAC Study Group of the Canadian HIV Trials Network. N Engl J Med 1994 330(6) 438-9. 

Of 26 patients who received rifabutin 600 mg/day in combination with ethambutol, streptomycin, and either clarithromycin (500 mg bd n — 15) or azithromycin (600 mg/day n — 11), there were rifabutin-related... 

Lalonde RG, Fanning MM, Tsoukas CM. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group. N Engl J Med 1996 335(6) 377-83. 

Unfortunately, MAC is resistant to the standard drugs used for tuberculosis, such as isoniazid and pyrazinamide. Multiple agents such as rifampin, rifabutin (ansamycin), clofazimine, imipenem, amikacin, ethambutol, ciprofloxacin, clarithromycin, and azithromycin have varying degrees of in vitro anti-MAC activity. Controversy formerly existed as to whether treatment for MAC is beneficial, but data indicate that an aggressive therapeutic approach decreases symptoms... 

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. 

Rifabutin is effective for the prevention of MAC infection in HIV-infected individuals. At a dose of 3(X) mg per day, rifabutin decreased the frequency of MAC bacteremia (2%). However, azithromycin or clarithromycin are more effective and less likely to interact with highly active antiretroviral therapy (HAART) drugs. Rifabutin also is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients, as it has a less profound CYP-dependent interaction with indinavir and nelfinavir. Rifabutin also is used in combination with clarithromycin and ethambutol for the therapy of MAC disease. 

M. avium complex Clarithromycin or azithromycin -1- ethambutol with or without rifabutin Rifabutin rifampin ethionamide cycloserine moxifloxacin or gatifloxacin... 

Clarithromycin (500 mg twice daily) or azithromycin (500 mg daily) is used in combination with ethambutol, with or without rifabutin, for treatment of MAC infection. Treatment should be lifelong in HIV-infected individuals. Azithromycin has minimal effect on drugs metabolized by CYP3A4. 

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. 

Drugs for M avium complex A combination of azithromycin or clarithromycin with ethambutol, with or without rifabutin, is favored. 

A) Amikacin, isoniazid, pyrazinamide, streptomycin Ciprofloxacin, cycloserine, isoniazid, PAS Ethambutol, isoniazid, rifabutin, streptomycin Ethambutol, pyrazinamide, rifampin, streptomycin Isoniazid, rifampin, pyrazinamide, ethambutol... 

Select an antibiotic regimen based on drug susceptibility of the cultured organism Start treatment with INH and pyrazinamide Treat the patient with clarithromycin, ethambutol, and rifabutin Treat with trimethoprim-sulfamethoxazole... 

MAC is much less susceptible than M tuberculosis to conventional antimycobacterial drugs. Both isoniazid and pyrazinamide have minimal activity against MAC. Currently, the optimum regimen consists of clarithromycin for azithromycin) with ethambutol and rifabutin. The answer is (D). 

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