Document 0009
 DOCN  M9590009
 TI    Intracellular activities of roxithromycin used alone and in association
       with other drugs against Mycobacterium avium complex in human
       macrophages.
 DT    9509
 AU    Rastogi N; Labrousse V; Bryskier A; Unite de la Tuberculose et des
       Mycobacteries, Institut Pasteur,; Pointe-a-Pitre, Guadeloupe, French
       West Indies.
 SO    Antimicrob Agents Chemother. 1995 Apr;39(4):976-8. Unique Identifier :
       AIDSLINE MED/95305561
 AB    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.
 DE    Antibiotics, Combined/*PHARMACOLOGY  Cells, Cultured  Human
       Macrophages/*MICROBIOLOGY  Mycobacterium avium Complex/*DRUG EFFECTS
       Roxithromycin/*PHARMACOLOGY  JOURNAL ARTICLE

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