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. 1994 Dec;38(12):2738–2742. doi: 10.1128/aac.38.12.2738

Effects of clarithromycin and rifabutin alone and in combination on intracellular and extracellular replication of Mycobacterium avium.

N Mor 1, J Vanderkolk 1, N Mezo 1, L Heifets 1
PMCID: PMC188278  PMID: 7695255

Abstract

The combined effect of clarithromycin and rifabutin against Mycobacterium avium multiplying either within human monocyte-derived macrophages or extracellularly in a liquid medium was additive: both MICs and MBCs were twofold lower for the combination than they were for each drug alone. Prolonged exposure for 4 weeks of M. avium-infected macrophages to combined concentrations that were only twofold greater than the MICs resulted in a 100-fold decrease in the number of viable bacteria, while in the drug-free controls a 100-fold or greater increase in comparison with the initial viable counts took place. Comparison of this effect with the results of the prolonged exposure to each drug alone suggested that under these experimental conditions rifabutin enhanced the antimicrobial activity of clarithromycin against intracellular bacteria. At the same time, inhibition of intracellular growth by a 2-h pulsed exposure of the infected macrophages to the combination of the two drugs was not different from the effect induced by clarithromycin alone. In conclusion, clarithromycin played the major role in the antimicrobial activity of the tested combination, while rifabutin may have enhanced this effect during a prolonged exposure of the intracellular bacteria to these two agents.

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Selected References

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

  1. Acocella G., Carlone N. A., Cuffini A. M., Cavallo G. The penetration of rifampicin, pyrazinamide, and pyrazinoic acid into mouse macrophages. Am Rev Respir Dis. 1985 Dec;132(6):1268–1273. doi: 10.1164/arrd.1985.132.6.1268. [DOI] [PubMed] [Google Scholar]
  2. Barradell L. B., Plosker G. L., McTavish D. Clarithromycin. A review of its pharmacological properties and therapeutic use in Mycobacterium avium-intracellulare complex infection in patients with acquired immune deficiency syndrome. Drugs. 1993 Aug;46(2):289–312. doi: 10.2165/00003495-199346020-00007. [DOI] [PubMed] [Google Scholar]
  3. Dhillon J., Mitchison D. A. Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M. tuberculosis and their penetration into mouse peritoneal macrophages. Am Rev Respir Dis. 1992 Jan;145(1):212–214. doi: 10.1164/ajrccm/145.1.212. [DOI] [PubMed] [Google Scholar]
  4. Heifets L. B., Iseman M. D., Lindholm-Levy P. J., Kanes W. Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods. Antimicrob Agents Chemother. 1985 Oct;28(4):570–575. doi: 10.1128/aac.28.4.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heifets L. B., Lindholm-Levy P. J., Comstock R. D. Bacteriostatic and bactericidal activities of gentamicin alone and in combination with clarithromycin against Mycobacterium avium. Antimicrob Agents Chemother. 1992 Aug;36(8):1695–1698. doi: 10.1128/aac.36.8.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Kent R. J., Bakhtiar M., Shanson D. C. The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare. J Antimicrob Chemother. 1992 Nov;30(5):643–650. doi: 10.1093/jac/30.5.643. [DOI] [PubMed] [Google Scholar]
  8. Mor N., Heifets L. Inhibition of intracellular growth of Mycobacterium avium by one pulsed exposure of infected macrophages to clarithromycin. Antimicrob Agents Chemother. 1993 Jun;37(6):1380–1382. doi: 10.1128/aac.37.6.1380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mor N., Heifets L. MICs and MBCs of clarithromycin against Mycobacterium avium within human macrophages. Antimicrob Agents Chemother. 1993 Jan;37(1):111–114. doi: 10.1128/aac.37.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mor N., Vanderkolk J., Heifets L. Accumulation of clarithromycin in macrophages infected with Mycobacterium avium. Pharmacotherapy. 1994 Jan-Feb;14(1):100–104. doi: 10.1002/j.1875-9114.1994.tb02793.x. [DOI] [PubMed] [Google Scholar]
  11. Mor N., Vanderkolk J., Heifets L. Inhibitory and bactericidal activities of levofloxacin against Mycobacterium tuberculosis in vitro and in human macrophages. Antimicrob Agents Chemother. 1994 May;38(5):1161–1164. doi: 10.1128/aac.38.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rastogi N., Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother. 1991 Mar;35(3):462–470. doi: 10.1128/aac.35.3.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rastogi N., Labrousse V., Goh K. S., De Sousa J. P. Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages. Antimicrob Agents Chemother. 1991 Dec;35(12):2473–2480. doi: 10.1128/aac.35.12.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]

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