Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages

Abstract

The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex. Intracellular bacteria were counted 60 min after inoculation. Extra- and intracellular bacteria were counted at days 4 and 7 after inoculation. The concentrations used were 4 micrograms of clarithromycin per ml (MICs for the three strains, 4, 4, and 4 micrograms/ml), 50 micrograms of sulfisoxazole per ml (MICs, 50, 25, and 25 micrograms/ml), and 0.5 micrograms of rifabutin per ml (MICs, 2, 0.5, and 0.5 micrograms/ml). Compared with controls, clarithromycin and rifabutin slowed the intracellular replication of the three strains (at day 7 after inoculation, P was less than 0.01 for the first strain and less than 0.001 for the two others). Sulfisoxazole was ineffective against the three strains. Clarithromycin was as effective as rifabutin. Clarithromycin plus rifabutin was as effective as each single agent. Clarithromycin plus sulfisoxazole was as effective as clarithromycin alone.