Document 1081
 DOCN  M9591081
 TI    In vitro and ex vivo activities of antimicrobial agents used in
       combination with clarithromycin, with or without amikacin, against
       Mycobacterium avium.
 DT    9509
 AU    Fattorini L; Li B; Piersimoni C; Tortoli E; Xiao Y; Santoro C; Ricci ML;
       Orefici G; Laboratory of Bacteriology and Medical Mycology, Istituto;
       Superiore di Sanita, Rome, Italy.
 SO    Antimicrob Agents Chemother. 1995 Mar;39(3):680-5. Unique Identifier :
       AIDSLINE MED/95314203
 AB    MICs of clarithromycin, amikacin, isoniazid, rifabutin, ciprofloxacin,
       sparfloxacin, ethambutol, and clofazimine were determined for six
       isolates of Mycobacterium avium complex (MAC) from AIDS patients both by
       the radiometric method and by an ex vivo model of infection in human
       macrophages. The median MICs in macrophages were similar or slightly
       lower than values found in broth, except for amikacin, which had
       slightly higher MICs inside the cells. Combinations of clarithromycin
       with other antimicrobial agents showed that clarithromycin-clofazimine
       and clarithromycin-rifabutin were synergistic on five of six strains
       while clarithromycin-amikacin and clarithromycin-isoniazid were
       antagonistic on one and two strains, respectively. The addition of
       amikacin made the combinations of clarithromycin-clofazimine and
       clarithromycin-ethambutol synergistic against all the MAC strains. In
       the macrophage model, the combination of clarithromycin-clofazimine
       (mean survival, 21%) and clarithromycin-rifabutin (mean survival, 29%)
       showed a strong reduction in viable counts compared with single drugs,
       while clarithromycin-amikacin was less active than single drugs alone.
       In general, the addition of amikacin did not improve the activity of the
       combinations, except for clarithromycin-isoniazid-amikacin (mean
       survival, 19%), which was significantly more active than either
       clarithromycin-isoniazid or clarithromycin-amikacin. The use of the
       macrophage model can suggest new combinations of antimicrobial agents
       with anti-MAC activity which, on the basis of their in vitro
       effectiveness, would probably be disregarded for assay in animal models.
 DE    Amikacin/METABOLISM/PHARMACOLOGY  Antibiotics,
       Combined/METABOLISM/*PHARMACOLOGY
       Clarithromycin/METABOLISM/PHARMACOLOGY  Human  In Vitro
       Macrophages/DRUG EFFECTS/METABOLISM/MICROBIOLOGY  Microbial Sensitivity
       Tests  Mycobacterium avium Complex/*DRUG EFFECTS  Mycobacterium
       avium-intracellulare Infection/*MICROBIOLOGY  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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