Document 0103
 DOCN  M9590103
 TI    Potential role of roxithromycin against the Mycobacterium avium complex.
 DT    9509
 AU    Young LS; Bermudez LE; Wu M; Inderlied CB; Kuzell Institute for
       Arthritis and Infectious Diseases,; California Pacific Medical Center
       Research Institute, San; Francisco 94115, USA.
 SO    Infection. 1995;23 Suppl 1:S28-32. Unique Identifier : AIDSLINE
       MED/95301322
 AB    Until the recent experience with azithromycin and clarithromycin,
       macrolides were not considered to be important agents against
       mycobacteria. Clinical evidence is now growing that the newer 14 and 15
       membered macrolide compounds have therapeutic activity against
       Mycobacterium avium, Mycobacterium chelonae and Mycobacterium leprae.
       Several years ago, when evaluating the activity of roxithromycin using
       one of the more virulent M. avium in our collection, the authors found
       that roxithromycin exerted a bacteriostatic effect in cultured human
       macrophages. However, in combination with tumour necrosis factor, which
       induces macrophage activation, roxithromycin caused enhanced
       intracellular killing. The significance of this finding is that tumour
       necrosis factor can be elaborated by activated macrophages during the
       course of infection. The roxithromycin doses that were chosen for these
       studies were less than achievable blood levels. More recently, the in
       vitro effect of roxithromycin against a panel of isolates from AIDS
       patients has been assessed and it was found that some (but not all) of
       the inhibitory concentrations, by the T-100 method of Inderlied, are
       within achievable serum levels. This, however, may not be the basis for
       anticipating in vivo activity since macrolide compounds are known to be
       concentrated within cells and particularly within phagolysosomes.
       Demonstration of effect in an in vitro test system is encouraging, but
       should be considered only as a preliminary step to careful assessments
       in experimental animals, such as the beige mouse, and studies in humans.
 DE    AIDS-Related Opportunistic Infections/MICROBIOLOGY  Female  Human
       Hydrogen-Ion Concentration  Macrophages/MICROBIOLOGY  Male  Microbial
       Sensitivity Tests/METHODS  Mycobacterium avium Complex/*DRUG EFFECTS
       Roxithromycin/*PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).