RIFABUTIN AND SPARFLOXACIN BUT NOT AZITHROMYCIN INHIBIT BINDING OF MYCOBACTERIUM-AVIUM COMPLEX TO HT-29 INTESTINAL MUCOSAL CELLS

Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointest inal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory con centrations of antibiotics which have anti-MAC activity in vitro affec t the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MI C, 2.6 mu g/ml), sparfloxacin (MIC, 8.4 mu g/ml), or azithromycin (MIC , 32 mu g/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then wa shed to remove unbound bacteria and were subsequently lysed. The numbe r of MAC isolates that bound to the HT-29 cells was determined by plat ing the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 mu g/ml reduced MAC bindin g to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 mu g/ml inhibited binding by 77 to 93%. Azithromycin at concentr ations of 2, 10, and 30 mu g/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin an d quinolones.