COMPARISON OF THE ACTIVITY OF FLUOROQUINOLONES AGAINST MYCOBACTERIUM-AVIUM IN CELL-FREE SYSTEMS AND A HUMAN MONOCYTE IN-VITRO INFECTION MODEL

Mycobacterium avium frequently causes disseminated infection in advanc ed AIDS. Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium activity in cell-free systems in vitro. Acidic conditio ns within macrophages and variable intracellular drug penetration and compartmentalization may, however, alter the susceptibility of M. aviu m to these antimicrobial agents in human tissues. We, therefore, teste d the activities of 47 quinolones against M. avium in a human monocyte infection model using ciprofloxacin susceptible (MIG = 0.25 mg/L) and resistant (MIG = 4 mg/L) patient isolates. Monocytes from healthy sub jects were infected with M. avium and cultured with or without antimic robials for 8 days. Some quinolones had poor activity against M. avium in the monocyte culture system despite low MICs (less than or equal t o 0.25 mg/L); in contrast, some quinolones with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at 4 mg/L. Six qui nolones synthesized based on structure-activity analysis were more act ive than ciprofloxacin. These data underscore the importance of evalua ting drug activity of new antimicrobial agents against intracellular p athogens in a macrophage model as well as in cell-free systems.