MAC infection

Prevention of disseminated Mycobacterium avium complex (MAC) infections 1,200 mg taken once weekly. 

Treatment of disseminated MAC infections 600 mg/day in combination with ethambutol at the recommended daily dose of 15 mg/kg. 

The incidence of disseminated MAC infection has increased dramatically with the AIDS epidemic. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50 X 10 /1 (11). In a randomized, open trial in 37 patients with HIV-associated disseminated MAC infection, treatment with clarithromycin -I- ethambutol produced more rapid resolution of bacteremia, and was more effective at sterilization of blood cultures after 16 weeks than azithromycin + ethambutol (12). 

In a randomized, double-bUnd, placebo-controlled multicenter trial in 174 HIV-infected patients with CD4 cell counts of under 100 x 10 /1, azithromycin (1200 mg once a week) was safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections (16). 

An interaction involving azithromycin with rifabutin, and less commonly rifampicin, was observed in patients with MAC infections (51). 

Organisms of the Mycobacterium avium complex (MAC) commonly cause disseminated bacterial infection among patients with AIDS. There is evidence that immunoprophylaxis against MAC infection may be possible. A heat-killed Mycobacterium vaccae vaccine was given in a three-dose schedule to 12 HIV-infected adults with CD4 cell counts below 300 x 10 /1 (107). The vaccine was well tolerated and produced detectable immunological responses in 3 of 11 subjects who completed the trial. 

Clarithromycin is one of the core drugs for MAC infections in both HIV-infected and non-infected patients. For this indication, doses of up to 2000 mg/day are used, typically in combination with other drugs. 

In patients with MAC infections taking rifabutin or rifampicin the addition of clarithromycin resulted in rifamycin-related adverse events in 77% of patients... 

Rifabutin has better activity against the minimum alveolar concentration (MAC) organisms than does rifampin. Rifabutin is active in vitro against MAC bacteria isolated from both HIV-infected (where the majority of MAC infections are M. avium) and non-HIV-infected individuals (in whom approximately 40% of MAC infections are M. intracellulare). Rifabutin inhibits the growth of most MAC isolates at concentrations ranging from 0.25 to 1 pg/mL. Rifabutin also inhibits the growth of many strains of M. tuberculosis at concentrations of 0.125 pg/mL. 

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. 

Clarithromycin has been shown to be an effective prophylactic agent against MAC infection in patients with advanced HIV infection. In a prospective, doubleblind, placebo-controlled trial, clarithromycin prevented 69% of the expected cases of MAC disease [64]. Other studies have demonstrated that clarithromycin alone or in combination with rifabutin prevents MAC infections in AIDS patients and prolongs survival [65, 66]. However, a large prospective study failed to show that the combination of clarithromycin plus rifabutin combination was more effective than clarithromycin alone [67]. Drug-resistant MAC has been reported in 29-58% of patients who developed disseminated infection while taking prophylaxis with clarithromycin [64, 67]. Resistance to clarithromycin and other macrolides is a serious potential problem due to cross-resistance with azithromycin that narrows the therapeutic options available for MAC disease [68]. 

Freedberg, K. A., Cohen, C. J., and Barber, T. W. (1997). Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS A cost-effectiveness analysis. J. Acquir. Immune Defic. Syndr. Hum. Retroviral. 15, 275-282. 

Use of clarithromycin or azithromycin alone is associated with the development of resistance, and they therefore should not be used as monotherapy of MAC infection. 

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. 

The high doses used to treat MAC infections rarely cause tinnitus, dizziness, and reversible hearing loss. 

Prophylaxis of MAC infection with clarithromycin or azithromycin should be strongly considered for HIV-infected persons whose CD4 count is <50/mm. ... 

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. 

Although rifabutin can lower elarithromyein levels, the efficacy of this combination for MAC infection is established, although not without risk, see Uveitis, below, elarithromyein raises rifabutin levels and therefore increases the risks of adverse effeets. Coneurrent use may therefore be desirable, but monitoring for adverse effeets is necessary. 

Infection with the human immunodeficiency virus (HIV) may produce isolated lymphadenopathy resulting from direct infection by the virus or from secondary infection (Radin 1995 Tarantino et al. 2003). Mesenteric lymphadenopathy in patients with HIV is far more likely to result from an opportunistic infection or even an underlying malignancy than to be caused by direct HIV infection. In this case, the lymph nodes may be enlarged but rarely massive. On the contrary, in HIV positive patients with a CD4 cell count of 50/mL or less, Mycobacterium avium complex (MAC) is the main cause of massive mesenteric lymphadenopathy. In HIV patients with mesenteric lymph nodes, in particular if forming a conglomerate mass, MAC infection should always be considered (Koh et al. 2003 Tarantino et al. 2003) (Fig. 2.9). 

Fig.2.9a,b. Mesenteric lymph nodes, forming a conglomerate mass, in HIV patient with MAC infection... 

RFB is a semisynthetic derivative of rifampin that is effective for the prophylaxis and treatment of Mycobacterium avimn complex (MAC) infection as well as M. tuberculosis [55 ]. Anterior uveitis and hypopyon are well-recognised and frequently reported complications of RFB treatment however, posterior involvement is relatively rare. Severe cases may develop dense vitritis with large yellow-white opacities or panuveitis resembling endophthalmitis [56 ]. 

---