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. 1990 Jun;34(6):967–970. doi: 10.1128/aac.34.6.967

Liposome-encapsulated-gentamicin therapy of Mycobacterium avium complex infection in beige mice.

S P Klemens 1, M H Cynamon 1, C E Swenson 1, R S Ginsberg 1
PMCID: PMC171739  PMID: 2393294

Abstract

The efficacy of liposome-encapsulated gentamicin and free gentamicin was evaluated with the beige (C57BL/6J-bgj/bgj) mouse model of disseminated Mycobacterium avium complex infection. Approximately 10(7) viable M. avium complex cells were given intravenously. Seven days later, treatment with either encapsulated or free gentamicin at 20 mg/kg of body weight was started. Treatment was given daily for 5 consecutive days or twice weekly for 3 weeks. The mice were sacrificed 5 days after the last dose. Spleens, livers, and lungs were homogenized, and viable cell counts were determined. An analysis of variance and subsequent Tukey honestly significant difference tests indicated that both encapsulated and free gentamicin reduced viable cell counts in each of the organs compared with no treatment. Encapsulated gentamicin significantly reduced viable cell counts in the spleen and liver compared with the free gentamicin. A dose-response experiment was performed with a daily dose of 0.2, 2, or 20 mg/kg. Dose-related reductions in viable cell counts were observed for spleens and livers, although none of the regimens resulted in sterilization of these organs. Liposome-encapsulated gentamicin should be considered for further evaluation in the treatment of M. avium complex infection in humans.

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Selected References

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

  1. Bermudez L. E., Wu M., Young L. S. Intracellular killing of Mycobacterium avium complex by rifapentine and liposome-encapsulated amikacin. J Infect Dis. 1987 Sep;156(3):510–513. doi: 10.1093/infdis/156.3.510. [DOI] [PubMed] [Google Scholar]
  2. Cynamon M. H., Swenson C. E., Palmer G. S., Ginsberg R. S. Liposome-encapsulated-amikacin therapy of Mycobacterium avium complex infection in beige mice. Antimicrob Agents Chemother. 1989 Aug;33(8):1179–1183. doi: 10.1128/aac.33.8.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. David H. L. Basis for lack of drug susceptibility of atypical mycobacteria. Rev Infect Dis. 1981 Sep-Oct;3(5):878–884. doi: 10.1093/clinids/3.5.878. [DOI] [PubMed] [Google Scholar]
  4. Davidson P. T., Khanijo V., Goble M., Moulding T. S. Treatment of disease due to Mycobacterium intracellulare. Rev Infect Dis. 1981 Sep-Oct;3(5):1052–1059. doi: 10.1093/clinids/3.5.1052. [DOI] [PubMed] [Google Scholar]
  5. Davis C. E., Jr, Carpenter J. L., Trevino S., Koch J., Ognibene A. J. In vitro susceptibility of Mycobacterium avium complex to antibacterial agents. Diagn Microbiol Infect Dis. 1987 Nov;8(3):149–155. doi: 10.1016/0732-8893(87)90165-9. [DOI] [PubMed] [Google Scholar]
  6. Dutt A. K., Stead W. W. Long-term results of medical treatment in Mycobacterium intracellulare infection. Am J Med. 1979 Sep;67(3):449–453. doi: 10.1016/0002-9343(79)90792-7. [DOI] [PubMed] [Google Scholar]
  7. Düzgüneş N., Perumal V. K., Kesavalu L., Goldstein J. A., Debs R. J., Gangadharam P. R. Enhanced effect of liposome-encapsulated amikacin on Mycobacterium avium-M. intracellulare complex infection in beige mice. Antimicrob Agents Chemother. 1988 Sep;32(9):1404–1411. doi: 10.1128/aac.32.9.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Etzkorn E. T., Aldarondo S., McAllister C. K., Matthews J., Ognibene A. J. Medical therapy of Mycobacterium avium-intracellulare pulmonary disease. Am Rev Respir Dis. 1986 Sep;134(3):442–445. doi: 10.1164/arrd.1986.134.3.442. [DOI] [PubMed] [Google Scholar]
  9. Gangadharam P. R., Candler E. R. In vitro anti-mycobacterial activity of some new amino-glycoside antibiotics. Tubercle. 1977 Mar;58(1):35–38. doi: 10.1016/s0041-3879(77)80008-1. [DOI] [PubMed] [Google Scholar]
  10. Gangadharam P. R., Kesavalu L., Rao P. N., Perumal V. K., Iseman M. D. Activity of amikacin against Mycobacterium avium complex under simulated in vivo conditions. Antimicrob Agents Chemother. 1988 Jun;32(6):886–889. doi: 10.1128/aac.32.6.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gangadharam P. R., Perumal V. K., Podapati N. R., Kesavalu L., Iseman M. D. In vivo activity of amikacin alone or in combination with clofazimine or rifabutin or both against acute experimental Mycobacterium avium complex infections in beige mice. Antimicrob Agents Chemother. 1988 Sep;32(9):1400–1403. doi: 10.1128/aac.32.9.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gruner S. M., Lenk R. P., Janoff A. S., Ostro M. J. Novel multilayered lipid vesicles: comparison of physical characteristics of multilamellar liposomes and stable plurilamellar vesicles. Biochemistry. 1985 Jun 4;24(12):2833–2842. doi: 10.1021/bi00333a004. [DOI] [PubMed] [Google Scholar]
  13. Horsburgh C. R., Jr, Mason U. G., 3rd, Heifets L. B., Southwick K., Labrecque J., Iseman M. D. Response to therapy of pulmonary Mycobacterium avium-intracellulare infection correlates with results of in vitro susceptibility testing. Am Rev Respir Dis. 1987 Feb;135(2):418–421. doi: 10.1164/arrd.1987.135.2.418. [DOI] [PubMed] [Google Scholar]
  14. Sanders W. E., Cacciatore R., Valdez H., Pejovic I., Dunbar F. P. Activity of gentamicin against mycobacteria in vitro and against Mycobacterium tuberculosis in mice. J Infect Dis. 1971 Dec;124 (Suppl):S33–S36. doi: 10.1093/infdis/124.supplement_1.s33. [DOI] [PubMed] [Google Scholar]
  15. Swenson C. E., Stewart K. A., Hammett J. L., Fitzsimmons W. E., Ginsberg R. S. Pharmacokinetics and in vivo activity of liposome-encapsulated gentamicin. Antimicrob Agents Chemother. 1990 Feb;34(2):235–240. doi: 10.1128/aac.34.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vladimirsky M. A., Ladigina G. A. Antibacterial activity of liposome-entrapped streptomycin in mice infected with mycobacterium tuberculosis. Biomed Pharmacother. 1982;36(8-9):375–377. [PubMed] [Google Scholar]
  17. Yatvin M. B., Lelkes P. I. Clinical prospects for liposomes. Med Phys. 1982 Mar-Apr;9(2):149–175. doi: 10.1118/1.595079. [DOI] [PubMed] [Google Scholar]
  18. 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]

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