Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy- clarithromycin against Mycobacterium avium complex in human macrophages

Y. Cohen, C. Perronne, C. Truffot-Pernot, J. Grosset, J. L. Vilde, J. J. Pocidalo -

Research output: Contribution to journalArticle

Abstract

The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 μg of WIN-57273 per ml (MICs for the two strains, 1 μg/ml), 4 μg of 14-OH clarithromycin per ml (MICs, 8 and 2 μg/ml, respectively, at pH 7.4), 4 μg of minocycline per ml (MICs, 64 and 32 μg/ml, respectively), and 4 μg of clarithromycin per ml (MICs, 2 and 0.5 μg/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN- 57273, minocycline (P < 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P < 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P < 0.02), clarithromycin (P < 0.02), 14-OH clarithromycin plus clarithromycin (P < 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14- OH clarithromycin (P < 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P < 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P < 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.

Original languageEnglish (US)
Pages (from-to)2104-2107
Number of pages4
JournalAntimicrobial agents and chemotherapy
Volume36
Issue number10
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy- clarithromycin against Mycobacterium avium complex in human macrophages'. Together they form a unique fingerprint.

  • Cite this