Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Aug;38(8):1721–1725. doi: 10.1128/aac.38.8.1721

Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice.

S P Klemens 1, M H Cynamon 1
PMCID: PMC284628  PMID: 7986001

Abstract

The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection.

Full text

PDF
1721

Selected References

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

  1. Assandri A., Ratti B., Cristina T. Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit. J Antibiot (Tokyo) 1984 Sep;37(9):1066–1075. doi: 10.7164/antibiotics.37.1066. [DOI] [PubMed] [Google Scholar]
  2. Bahal N., Nahata M. C. The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin. Ann Pharmacother. 1992 Jan;26(1):46–55. doi: 10.1177/106002809202600112. [DOI] [PubMed] [Google Scholar]
  3. Chave J. P., Munafo A., Chatton J. Y., Dayer P., Glauser M. P., Biollaz J. Once-a-week azithromycin in AIDS patients: tolerability, kinetics, and effects on zidovudine disposition. Antimicrob Agents Chemother. 1992 May;36(5):1013–1018. doi: 10.1128/aac.36.5.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cynamon M. H. Comparative in vitro activities of MDL 473, rifampin, and ansamycin against Mycobacterium intracellulare. Antimicrob Agents Chemother. 1985 Sep;28(3):440–441. doi: 10.1128/aac.28.3.440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cynamon M. H., Klemens S. P. Activity of azithromycin against Mycobacterium avium infection in beige mice. Antimicrob Agents Chemother. 1992 Aug;36(8):1611–1613. doi: 10.1128/aac.36.8.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cynamon M. H., Klemens S. P., Grossi M. A. Comparative activities of azithromycin and clarithromycin against Mycobacterium avium infection in beige mice. Antimicrob Agents Chemother. 1994 Jul;38(7):1452–1454. doi: 10.1128/aac.38.7.1452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Dickinson J. M., Mitchison D. A. In vitro properties of rifapentine (MDL473) relevant to its use in intermittent chemotherapy of tuberculosis. Tubercle. 1987 Jun;68(2):113–118. doi: 10.1016/0041-3879(87)90026-2. [DOI] [PubMed] [Google Scholar]
  9. Foulds G., Shepard R. M., Johnson R. B. The pharmacokinetics of azithromycin in human serum and tissues. J Antimicrob Chemother. 1990 Jan;25 (Suppl A):73–82. doi: 10.1093/jac/25.suppl_a.73. [DOI] [PubMed] [Google Scholar]
  10. Girard A. E., Girard D., English A. R., Gootz T. D., Cimochowski C. R., Faiella J. A., Haskell S. L., Retsema J. A. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution. Antimicrob Agents Chemother. 1987 Dec;31(12):1948–1954. doi: 10.1128/aac.31.12.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heifets L. B., Lindholm-Levy P. J., Comstock R. D. Clarithromycin minimal inhibitory and bactericidal concentrations against Mycobacterium avium. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856–858. doi: 10.1164/ajrccm/145.4_Pt_1.856. [DOI] [PubMed] [Google Scholar]
  12. Ji B., Truffot-Pernot C., Lacroix C., Raviglione M. C., O'Brien R. J., Olliaro P., Roscigno G., Grosset J. Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1541–1546. doi: 10.1164/ajrccm/148.6_Pt_1.1541. [DOI] [PubMed] [Google Scholar]
  13. Kirst H. A., Sides G. D. New directions for macrolide antibiotics: pharmacokinetics and clinical efficacy. Antimicrob Agents Chemother. 1989 Sep;33(9):1419–1422. doi: 10.1128/aac.33.9.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klemens S. P., Cynamon M. H. Activity of rifapentine against Mycobacterium avium infection in beige mice. J Antimicrob Chemother. 1992 May;29(5):555–561. doi: 10.1093/jac/29.5.555. [DOI] [PubMed] [Google Scholar]
  15. Klemens S. P., Cynamon M. H. In vivo activities of newer rifamycin analogs against Mycobacterium avium infection. Antimicrob Agents Chemother. 1991 Oct;35(10):2026–2030. doi: 10.1128/aac.35.10.2026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klemens S. P., DeStefano M. S., Cynamon M. H. Activity of clarithromycin against Mycobacterium avium complex infection in beige mice. Antimicrob Agents Chemother. 1992 Nov;36(11):2413–2417. doi: 10.1128/aac.36.11.2413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klemens S. P., Grossi M. A., Cynamon M. H. Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex. Antimicrob Agents Chemother. 1994 Feb;38(2):234–237. doi: 10.1128/aac.38.2.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Retsema J. A., Girard A. E., Girard D., Milisen W. B. Relationship of high tissue concentrations of azithromycin to bactericidal activity and efficacy in vivo. J Antimicrob Chemother. 1990 Jan;25 (Suppl A):83–89. doi: 10.1093/jac/25.suppl_a.83. [DOI] [PubMed] [Google Scholar]
  19. Young L. S., Wiviott L., Wu M., Kolonoski P., Bolan R., Inderlied C. B. Azithromycin for treatment of Mycobacterium avium-intracellulare complex infection in patients with AIDS. Lancet. 1991 Nov 2;338(8775):1107–1109. doi: 10.1016/0140-6736(91)91965-w. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES