IN-VITRO ACTIVITIES OF RIFABUTIN, AZITHROMYCIN, CIPROFLOXACIN, CLARITHROMYCIN, CLOFAZIMINE, ETHAMBUTOL, AND AMIKACIN IN COMBINATIONS OF 2, 3, AND 4 DRUGS AGAINST MYCOBACTERIUM-AVIUM

Multidrug therapy is recommended for treatment of Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. Azithromycin, clarithr omycin, rifabutin, ciprofloxacin, ethambutol, clofazimine, and amikaci n have all been suggested for use in treating MAC bacteremia, but the most active combinations of these drugs have not been identified, nor has the minimum number of drugs needed for effective therapy been dete rmined. To address the former, the in vitro bactericidal activities of all two-, three-, and four-drug combinations of these seven agents wa s determined by using 10 blood-derived strains of MAC isolated from pa tients with AIDS. The activities of the 132 drug combinations were com pared by statistical analysis of survival means (analysis of variance) and further evaluated by determining the percentage of strains consid ered susceptible to each combination. When susceptibility was defined as a decrease in CFU of greater than or equal to 2 log(10), no two- or three-drug combination and only two four-drug combinations were activ e against all 10 MAC strains. When a less stringent definition was app lied (greater than or equal to 1 log(10) decrease in CFU), 1 two-drug combination, 9 three-drug combinations, and 31 four-drug combinations showed activity against all 10 strains. Eighteen selected drug combina tions were also tested for intracellular activity in MAC-infected J774 cells. Combinations which contained amikacin as a component were cons iderably less active against intracellular MAC organisms than against organisms in broth. The opposite result was obtained for the combinati on of clarithromycin plus clofazimine.