The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare

Abstract

The in-vitro activities of five antimicrobial agents (rifabutin, clarithromycin, ethambutol, ciprofloxacin and amikacin), alone and in combination, were evaluated against 21 strains of Mycobacterium avium-intracellulare isolated from patients with AIDS. The combined activities of these agents were studied on solid medium by a full chequerboard method. Synergy was demonstrated most frequently (28–71% of isolates) with those combinations that included ethambutol. In killing curve experiments where double and triple combinations of agents were tested against two of the strains, 99% kill was achieved in seven days at concentrations well below those that are attainable in serum. However, an additive rather than a synergic effect was seen in most instances. Although ciprofloxacin alone had the greatest bactericidal activity against these two strains, its activity was antagonized in the presence of rifabutin this antagonism became inapparent when a third agent was added. Demonstration of bactericidal activity in broth culture may be more relevant than the results of susceptibility testing on solid medium when choosing antimicrobial therapy for patients with this infection.