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. 1991 Oct;35(10):2026–2030. doi: 10.1128/aac.35.10.2026

In vivo activities of newer rifamycin analogs against Mycobacterium avium infection.

S P Klemens 1, M H Cynamon 1
PMCID: PMC245319  PMID: 1662021

Abstract

The comparative activities of newer rifamycin analogs and the activity of rifabutin or rifapentine in combination with other antimycobacterial agents was evaluated in the beige (C57BL/6J; bgj/bgj) mouse model of disseminated Mycobacterium avium infection. Rifabutin and rifapentine at 20 mg/kg of body weight had comparable activities. P/DEA and CGP 7040 at 20 mg/kg were less active. The combination of ethambutol at 125 mg/kg and rifabutin at 20 mg/kg resulted in a slight increase in activity beyond that seen with rifabutin alone against organisms in the spleens. The combination of ethambutol and rifapentine at 20 mg/kg resulted in a modest increase in activity beyond that seen with rifapentine alone against organisms in the lungs. The combination of ethionamide at 125 mg/kg and rifapentine resulted in a decrease in activity compared with that for rifapentine alone. The combination of clofazimine at 20 mg/kg and rifapentine resulted in increased activity in the mouse model. The combination of clofazimine and rifapentine (or rifabutin) appears to be an attractive regimen that should be evaluated for the treatment of human infections due to M. avium complex.

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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. Cavalleri B., Turconi M., Tamborini G., Occelli E., Cietto G., Pallanza R., Scotti R., Berti M., Romanó G., Parenti F. Synthesis and biological activity of some derivatives of rifamycin P. J Med Chem. 1990 May;33(5):1470–1476. doi: 10.1021/jm00167a029. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Dickinson J. M., Mitchison D. A. In vitro activity of new rifamycins against rifampicin-resistant M. tuberculosis and MAIS-complex mycobacteria. Tubercle. 1987 Sep;68(3):177–182. doi: 10.1016/0041-3879(87)90053-5. [DOI] [PubMed] [Google Scholar]
  5. Easmon C. S., Crane J. P. Comparative uptake of rifampicin and rifapentine (DL473) by human neutrophils. J Antimicrob Chemother. 1984 Jun;13(6):585–591. doi: 10.1093/jac/13.6.585. [DOI] [PubMed] [Google Scholar]
  6. Gangadharam P. R., Perumal V. K., Jairam B. T., Rao P. N., Nguyen A. K., Farhi D. C., Iseman M. D. Activity of rifabutin alone or in combination with clofazimine or ethambutol or both against acute and chronic experimental Mycobacterium intracellulare infections. Am Rev Respir Dis. 1987 Aug;136(2):329–333. doi: 10.1164/ajrccm/136.2.329. [DOI] [PubMed] [Google Scholar]
  7. Heifets L. B., Iseman M. D. Determination of in vitro susceptibility of mycobacteria to ansamycin. Am Rev Respir Dis. 1985 Sep;132(3):710–711. doi: 10.1164/arrd.1985.132.3.710. [DOI] [PubMed] [Google Scholar]
  8. Heifets L. B., Iseman M. D., Lindholm-Levy P. J. Combinations of rifampin or rifabutine plus ethambutol against Mycobacterium avium complex. Bactericidal synergistic, and bacteriostatic additive or synergistic effects. Am Rev Respir Dis. 1988 Mar;137(3):711–715. doi: 10.1164/ajrccm/137.3.711. [DOI] [PubMed] [Google Scholar]
  9. Heifets L. B., Lindholm-Levy P. J., Flory M. A. Bactericidal activity in vitro of various rifamycins against Mycobacterium avium and Mycobacterium tuberculosis. Am Rev Respir Dis. 1990 Mar;141(3):626–630. doi: 10.1164/ajrccm/141.3.626. [DOI] [PubMed] [Google Scholar]
  10. Heifets L. B. Synergistic effect of rifampin, streptomycin, ethionamide, and ethambutol on Mycobacterium intracellulare. Am Rev Respir Dis. 1982 Jan;125(1):43–48. doi: 10.1164/arrd.1982.125.1.43. [DOI] [PubMed] [Google Scholar]
  11. Klemens S. P., Cynamon M. H., Swenson C. E., Ginsberg R. S. Liposome-encapsulated-gentamicin therapy of Mycobacterium avium complex infection in beige mice. Antimicrob Agents Chemother. 1990 Jun;34(6):967–970. doi: 10.1128/aac.34.6.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kuze F., Kurasawa T., Bando K., Lee Y., Maekawa N. In vitro and in vivo susceptibility of atypical mycobacteria to various drugs. Rev Infect Dis. 1981 Sep-Oct;3(5):885–897. doi: 10.1093/clinids/3.5.885. [DOI] [PubMed] [Google Scholar]
  13. Ozenne G., Morel A., Menard J. F., Thauvin C., Samain J. P., Lemeland J. F. Susceptibility of Mycobacterium avium complex to various two-drug combinations of antituberculosis agents. Am Rev Respir Dis. 1988 Oct;138(4):878–881. doi: 10.1164/ajrccm/138.4.878. [DOI] [PubMed] [Google Scholar]
  14. Pascual A., Tsukayama D., Kovarik J., Gekker G., Peterson P. Uptake and activity of rifapentine in human peritoneal macrophages and polymorphonuclear leukocytes. Eur J Clin Microbiol. 1987 Apr;6(2):152–157. doi: 10.1007/BF02018197. [DOI] [PubMed] [Google Scholar]
  15. Saito H., Sato K., Tomioka H. Comparative in vitro and in vivo activity of rifabutin and rifampicin against Mycobacterium avium complex. Tubercle. 1988 Sep;69(3):187–192. doi: 10.1016/0041-3879(88)90020-7. [DOI] [PubMed] [Google Scholar]
  16. Shronts J. S., Rynearson T. K., Wolinsky E. Rifampin alone and combined with other drugs in Mycobacterium kansasii and Mycobacterium intracellulare infections of mice. Am Rev Respir Dis. 1971 Nov;104(5):728–741. doi: 10.1164/arrd.1971.104.5.728. [DOI] [PubMed] [Google Scholar]
  17. Skinner M. H., Hsieh M., Torseth J., Pauloin D., Bhatia G., Harkonen S., Merigan T. C., Blaschke T. F. Pharmacokinetics of rifabutin. Antimicrob Agents Chemother. 1989 Aug;33(8):1237–1241. doi: 10.1128/aac.33.8.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yajko D. M., Kirihara J., Sanders C., Nassos P., Hadley W. K. Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome. Antimicrob Agents Chemother. 1988 Sep;32(9):1392–1395. doi: 10.1128/aac.32.9.1392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Young L. S. Mycobacterium avium complex infection. J Infect Dis. 1988 May;157(5):863–867. doi: 10.1093/infdis/157.5.863. [DOI] [PubMed] [Google Scholar]
  20. Zimmer B. L., DeYoung D. R., Roberts G. D. In vitro synergistic activity of ethambutol, isoniazid, kanamycin, rifampin, and streptomycin against Mycobacterium avium-intracellulare complex. Antimicrob Agents Chemother. 1982 Jul;22(1):148–150. doi: 10.1128/aac.22.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]

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