INTRACELLULAR ACTIVITIES OF ROXITHROMYCIN USED ALONE AND IN ASSOCIATION WITH OTHER DRUGS AGAINST MYCOBACTERIUM-AVIUM COMPLEX IN HUMAN MACROPHAGES

Recent reports have shown that roxithromycin possesses significant act ivity against atypical mycobacteria, including the Mycobacterium avium complex (MAC), and that its extracellular anti-MAC activity is furthe r enhanced in two- or three-drug combinations with ethambutol, rifampi n, amikacin, ofloxacin, and clofazimine. In accordance with the above- mentioned antituberculous drugs were screened intracellularly against five clinical MAC isolates (from both human immunodeficiency virus-pos itive and human immunodeficiency virus-negative patients), phagocytize d by human monocyte-derived macrophages. The results showed that roxit hromycin used alone and within clinically achievable levels was active against all of the MAC isolates tested. Screening of two-drug combina tions showed that both rifampin and clofazimine further increased the intracellular activity of roxithromycin against all five isolates by 3 5 to 80% (ethambutol, ofloxacin, and amikacin resulted in increased in tracellular activity against one, two, and four isolates, respectively ). For the three-drug combinations, the combination fo roxithromycin p lus ethambutol used with rifampin or clofazimine was the most uniforml y active against all five MAC isolates, with activity increases of 42 to 90%, followed by roxithromycin plus ethambutol used with amikacin, which resulted in activity increases of 15 to 90%. The overall level o f intracellular killing after 5 days of drug addition, in comparison w ith growth in untreated controls, varied from 1 to 3 log units dependi ng on the individual MAC isolate and/or drug combination used.