Prevention of the selection of clarithromycin-resistant Mycobacterium avium-intracellulare complex

The prevalence of clarithromycin-resistant mutants in untreated bacterial populations of Mycobacterium avium-intracellulare complex (MAC) has been demonstrated to be between 10^-7 and 10^-8 colony forming units (CFUs) in the beige mouse model. Selection of these mutants occurred during clarithromycin monotherapy if treatment was initiated when the bacterial population size reached ≃ 10⁸ CFUs per spleen. Likewise, selection of clarithromycin-resistant MAC was induced in AIDS patients during therapy with clarithromycin alone or in combination with drugs that were ineffective for the treatment or prevention of MAC infection. Because the emergence of clarithromycin resistance during preventive therapy was observed exclusively in AIDS patients with CD4+ cell counts ≤ 25 cells/μl, clarithromycin monotherapy can be recommended for the prevention of MAC infection in AIDS patients with CD4+ cell counts of ≤ 50 cells/μl. However, a clarithromycin-containing combination regimen is recommended for patients with CD4+ cell counts < 50 cells/μl. Since preliminary animal experiments and clinical trials indicate that amikacin, ethambutol or rifabutin in combination with clarithromycin may prevent, or at least delay, the selection of clarithromycin-resistant mutants, further preventive trials are urgently needed to confirm these observations.