ACTIVITY OF RIFABUTIN, CLARITHROMYCIN, ETHAMBUTOL, SPARFLOXACIN AND AMIKACIN, ALONE AND IN COMBINATION, AGAINST MYCOBACTERIUM-AVIUM COMPLEXIN HUMAN MACROPHAGES

Disseminated infection with Mycobacterium avium complex (MAC) in patie nts with AIDS is currently treated with a combination of antimycobacte rial agents in order to prevent the selection of resistant mutant stra ins. Although clinical and microbiological responses can generally be achieved within a few weeks, relapses are common and require modificat ion of the combination regimen or identification of effective alternat e therapies. In this study we investigated the activities of rifabutin 0.5 mg/L, sparfloxacin 1 mg/L, clarithromycin 4 mg/L, amikacin 16 mg/ L and ethambutol 2 mg/L, alone and in combination, against nine strain s of M. avium isolated from the blood of patients with AIDS in order t o identify regimens with the greatest therapeutic potential. Macrophag es derived from human monocytes were infected with M. avium and inocul ated with a single drug or a combination of drugs; cfu counts were per formed at 0, 4 and 7 days after infection. At day 4 and at day 7, the combination of rifabutin, clarithromycin, amikacin and sparfloxacin di splayed the highest degree of activity. However, the activity did not differ significantly from that of the combination of rifabutin, clarit hromycin and ethambutol. The results of this study confirm the activit y of combinations including rifabutin and clarithromycin (+/-ethambuto l) in human monocyte-derived macrophages and suggest potentially usefu l associations in incorporating sparfloxacin and amikacin.