title: Intracellular activities of roxithromycin used alone and in association with other drugs against Mycobacterium avium complex in human macrophages.
abstract: Recent reports have shown that roxithromycin possesses significant activity against atypical mycobacteria, including the Mycobacterium avium complex (MAC), and that its extracellular anti-MAC activity is further enhanced in two- or three-drug combinations with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine. In accordance with the above data, the anti-MAC potential of roxithromycin used alone and in combination with the above-mentioned antituberculous drugs was screened intracellularly against five clinical MAC isolates (from both human immunodeficiency virus-positive and human immunodeficiency virus-negative patients), phagocytized by human monocyte-derived macrophages. The results showed that roxithromycin used alone and within clinically achievable levels was active against all of the MAC isolates tested. Screening of two-drug combinations showed that both rifampin and clofazimine further increased the intracellular activity of roxithromycin against all five isolates by 35 to 80% (ethambutol, ofloxacin, and amikacin resulted in increased intracellular activity against one, two, and four isolates, respectively). For the three-drug combinations, the combination of roxithromycin plus ethambutol used with rifampin or clofazimine was the most uniformly 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 of intracellular killing after 5 days of drug addition, in comparison with growth in untreated controls, varied from 1 to 3 log units depending on the individual MAC isolate and/or drug combination used.
authors.affiliation: Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Pointe-à-Pitre, Guadeloupe, French West Indies.
authors.forename: N
authors.initials: N
authors.lastname: Rastogi
authors.forename: V
authors.initials: V
authors.lastname: Labrousse
authors.forename: A
authors.initials: A
authors.lastname: Bryskier
mesh_terms: D002478:Cells, Cultured; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D015575:Roxithromycin / Q000494:pharmacology*
chemical_list: D015575:Roxithromycin