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. 1992 Oct;36(10):2104–2107. doi: 10.1128/aac.36.10.2104

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

Y Cohen 1, C Perronne 1, C Truffot-Pernot 1, J Grosset 1, J L Vilde 1, J J Pocidalo 1
PMCID: PMC245463  PMID: 1332586

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 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Crowle A. J., Elkins N., May M. H. Effectiveness of ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium, and rifampin against M. tuberculosis in cultured human macrophages. Am Rev Respir Dis. 1988 May;137(5):1141–1146. doi: 10.1164/ajrccm/137.5.1141. [DOI] [PubMed] [Google Scholar]
  2. Crowle A. J., Poche P. Inhibition by normal human serum of Mycobacterium avium multiplication in cultured human macrophages. Infect Immun. 1989 Apr;57(4):1332–1335. doi: 10.1128/iai.57.4.1332-1335.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dabernat H., Delmas C., Seguy M., Fourtillan J. B., Girault J., Lareng M. B. The activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae, determined by in-vitro and serum bactericidal tests. J Antimicrob Chemother. 1991 Feb;27 (Suppl A):19–30. doi: 10.1093/jac/27.suppl_a.19. [DOI] [PubMed] [Google Scholar]
  4. Dautzenberg B., Truffot C., Legris S., Meyohas M. C., Berlie H. C., Mercat A., Chevret S., Grosset J. Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):564–569. doi: 10.1164/ajrccm/144.3_Pt_1.564. [DOI] [PubMed] [Google Scholar]
  5. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am Rev Respir Dis. 1990 Oct;142(4):940–953. doi: 10.1164/ajrccm/142.4.940. [DOI] [PubMed] [Google Scholar]
  6. Ellner J. J., Goldberger M. J., Parenti D. M. Mycobacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. J Infect Dis. 1991 Jun;163(6):1326–1335. doi: 10.1093/infdis/163.6.1326. [DOI] [PubMed] [Google Scholar]
  7. Fernandes P. B., Hardy D. J., McDaniel D., Hanson C. W., Swanson R. N. In vitro and in vivo activities of clarithromycin against Mycobacterium avium. Antimicrob Agents Chemother. 1989 Sep;33(9):1531–1534. doi: 10.1128/aac.33.9.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heifets L. B., Lindholm-Levy P. J. MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis. Antimicrob Agents Chemother. 1990 May;34(5):770–774. doi: 10.1128/aac.34.5.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Horsburgh C. R., Jr Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med. 1991 May 9;324(19):1332–1338. doi: 10.1056/NEJM199105093241906. [DOI] [PubMed] [Google Scholar]
  10. Ji B., Perani E. G., Grosset J. H. Effectiveness of clarithromycin and minocycline alone and in combination against experimental Mycobacterium leprae infection in mice. Antimicrob Agents Chemother. 1991 Mar;35(3):579–581. doi: 10.1128/aac.35.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Perronne C., Gikas A., Truffot-Pernot C., Grosset J., Pocidalo J. J., Vilde J. L. Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages. Antimicrob Agents Chemother. 1990 Aug;34(8):1508–1511. doi: 10.1128/aac.34.8.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Perronne C., Gikas A., Truffot-Pernot C., Grosset J., Vilde J. L., Pocidalo J. J. Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages. Antimicrob Agents Chemother. 1991 Jul;35(7):1356–1359. doi: 10.1128/aac.35.7.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Truffot-Pernot C., Ji B., Grosset J. Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex. Antimicrob Agents Chemother. 1991 Aug;35(8):1677–1678. doi: 10.1128/aac.35.8.1677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tsukamura M. In-vitro antimycobacterial activity of minocycline. Tubercle. 1980 Mar;61(1):37–38. doi: 10.1016/0041-3879(80)90058-6. [DOI] [PubMed] [Google Scholar]
  15. Tucker S. B., Pierre R. V., Jordon R. E. Rapid identification of monocytes in a mixed mononuclear cell preparation. J Immunol Methods. 1977;14(3-4):267–269. doi: 10.1016/0022-1759(77)90137-5. [DOI] [PubMed] [Google Scholar]

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