Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Nov;33(11):1975–1979. doi: 10.1128/aac.33.11.1975

Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.

R H Rubin 1, P Lynch 1, M S Pasternack 1, D Schoenfeld 1, D N Medearis Jr 1
PMCID: PMC172798  PMID: 2558616

Abstract

The efficacy of treatment with ganciclovir (DHPG) and antibody activity-containing ascitic fluid (AF) separately and in combination was studied in normal and immunosuppressed BALB/c mice challenged intraperitoneally with a lethal dose (10(6) PFU) of murine cytomegalovirus (CMV). With combination therapy, lower doses of both DHPG and AF were often as effective as a higher dose of either agent given singly. For instance, the survival rate of murine CMV-challenged immunosuppressed mice was doubled when 4 mg of DHPG per kg and a 1:16 dilution of AF were both administered in contrast to when each was used alone. In both groups of animals, combination therapy was shown to be more effective than either therapy individually, even when initiation of therapy was delayed as long as 48 h. Such an approach holds promise for decreasing the expense associated with antibody use and the dose-related toxicity associated with DHPG use while maintaining or possibly increasing the efficacy of prophylaxis and therapy of serious CMV disease in humans.

Full text

PDF
1975

Selected References

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

  1. Chachoua A., Dieterich D., Krasinski K., Greene J., Laubenstein L., Wernz J., Buhles W., Koretz S. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (ganciclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. Ann Intern Med. 1987 Aug;107(2):133–137. doi: 10.7326/0003-4819-107-2-133. [DOI] [PubMed] [Google Scholar]
  2. Chou T. C., Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. doi: 10.1016/0065-2571(84)90007-4. [DOI] [PubMed] [Google Scholar]
  3. Emanuel D., Cunningham I., Jules-Elysee K., Brochstein J. A., Kernan N. A., Laver J., Stover D., White D. A., Fels A., Polsky B. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med. 1988 Nov 15;109(10):777–782. doi: 10.7326/0003-4819-109-10-777. [DOI] [PubMed] [Google Scholar]
  4. Frank I., Friedman H. M. Progress in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1988 Nov 15;109(10):769–771. doi: 10.7326/0003-4819-109-10-769. [DOI] [PubMed] [Google Scholar]
  5. Grundy J. E., Shanley J. D., Griffiths P. D. Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition? Lancet. 1987 Oct 31;2(8566):996–999. doi: 10.1016/s0140-6736(87)92560-8. [DOI] [PubMed] [Google Scholar]
  6. Keay S., Bissett J., Merigan T. C. Ganciclovir treatment of cytomegalovirus infections in iatrogenically immunocompromised patients. J Infect Dis. 1987 Dec;156(6):1016–1021. doi: 10.1093/infdis/156.6.1016. [DOI] [PubMed] [Google Scholar]
  7. Meyers J. D., Flournoy N., Thomas E. D. Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis. 1986 Mar;153(3):478–488. doi: 10.1093/infdis/153.3.478. [DOI] [PubMed] [Google Scholar]
  8. Reed E. C., Bowden R. A., Dandliker P. S., Lilleby K. E., Meyers J. D. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann Intern Med. 1988 Nov 15;109(10):783–788. doi: 10.7326/0003-4819-109-10-783. [DOI] [PubMed] [Google Scholar]
  9. Rubin R. H., Wilson E. J., Barrett L. V., Medearis D. N. Primary cytomegalovirus infection following cardiac transplantation in a murine model. Transplantation. 1984 Mar;37(3):306–310. doi: 10.1097/00007890-198403000-00018. [DOI] [PubMed] [Google Scholar]
  10. Rubin R. H., Wilson E. J., Barrett L. V., Medearis D. N. The protective effects of hyperimmune anti-murine cytomegalovirus antiserum against lethal viral challenge: the case for passive-active immunization. Clin Immunol Immunopathol. 1986 Apr;39(1):151–158. doi: 10.1016/0090-1229(86)90214-x. [DOI] [PubMed] [Google Scholar]
  11. Shanley J. D., Jordan M. C., Cook M. L., Stevens J. G. Pathogenesis of reactivated latent murine cytomegalovirus infection. Am J Pathol. 1979 Apr;95(1):67–80. [PMC free article] [PubMed] [Google Scholar]
  12. Shepp D. H., Dandliker P. S., de Miranda P., Burnette T. C., Cederberg D. M., Kirk L. E., Meyers J. D. Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1985 Sep;103(3):368–373. doi: 10.7326/0003-4819-103-3-368. [DOI] [PubMed] [Google Scholar]
  13. Snydman D. R., Werner B. G., Heinze-Lacey B., Berardi V. P., Tilney N. L., Kirkman R. L., Milford E. L., Cho S. I., Bush H. L., Jr, Levey A. S. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med. 1987 Oct 22;317(17):1049–1054. doi: 10.1056/NEJM198710223171703. [DOI] [PubMed] [Google Scholar]
  14. Wilson E. J., Medearis D. N., Jr, Hansen L. A., Rubin R. H. 9-(1-3-Dihydroxy-2-propoxymethyl)guanine prevents death but not immunity in murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice. Antimicrob Agents Chemother. 1987 Jul;31(7):1017–1020. doi: 10.1128/aac.31.7.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Winston D. J., Ho W. G., Lin C. H., Bartoni K., Budinger M. D., Gale R. P., Champlin R. E. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann Intern Med. 1987 Jan;106(1):12–18. doi: 10.7326/0003-4819-106-1-12. [DOI] [PubMed] [Google Scholar]

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

RESOURCES