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Treatment of systemic candidiasis in a neutropenic murine model using immunoglobulin G bearing liposomal amphotericin B

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Abstract

Efficacy of immunoglobulin G (IgG) bearing liposomal amphotericin B (LAMB-IgG), liposomal amphotericin B without IgG (LAMB) or free amphotericin B (fAMB/Fungizone) was investigated in the treatment of systemic candidiasis in a neutropenic mouse model. Treatment with a single dose (0.6 or 0.9 mg amphotericin B per kg body weight) of LAMB-IgG resulted in a significant increase in the survival rate of neutropenic mice infected with 3×105 cfu ofCandida albicans compared to untreated controls, mice injected with IgG, or liposome alone. Survival was also better in neutropenic mice treated with LAMB-IgG than in neutropenic mice treated with the same dose of LAMB or fAMB. Moreover, 65% of all mice survived the infection after treatment with a single dose of 0.6 mg AMB of the LAMB-IgG formulation. Quantitative culture counts of organs showed that both fAMB and LABM-IgG formulations even at a dose of 0.3 mg AMB/kg, clearedC. albicans from the spleens, livers, and lungs but not from the kidneys. However, a decreasd number ofC. albicans cells was recovered from the kidneys of mice that survived the infection. Results of the study suggest that LAMB-IgG is more effective than LAMB or fAMB in the therapy of disseminated candidiasis in neutropenic mice.

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References

  1. 1.

    Armstrong D. Life-threatening opportunistic fungal infections in patients with the acquired immunodeficiency syndrome. Ann NY Acad Sci 1988; 544: 443–50.

  2. 2.

    Bodey GP. Fungal infections in cancer patients. Ann NY Sci 1988; 544: 431–42.

  3. 3.

    Bodey GP. Candidiasis in cancer patients. Am J Med 1984; 77(4D): 13–19.

  4. 4.

    Mirskey HS, Cuttner J. Fungal infections in acute leukemia. Cancer 1972; 30: 348–352.

  5. 5.

    Myers JD, Atkinson K. Infection in bone marrow transplantation. Haematology 1983; 12: 791–811.

  6. 6.

    Lopez-Berestein G, Hopfer RL, Mehta R, Mehta K, Hersch EM, Juliano RL. Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice. J Infect Dis 1984; 150: 278–83.

  7. 7.

    Taylor RL, Williams DM, Craven PC, Graybill JR, Drutz DJ, Magee WE. Amphotericin B in liposomes: A novel therapy for histoplasmosis. Am Rev Respir Dis 1982; 125: 610–11.

  8. 8.

    Graybill JR, Craven PC, Taylor RL, Williams DM, Magee WE. Treatment of murine cryptococcosis with liposome-associated amphotericin B J Infect Dis 1982; 145: 748–52.

  9. 9.

    Lopez-Brestein G. Treatment of systemic fungal infections with liposomal amphotericin B. In Lopez-Berestein G, Fidler IJ (eds.), Liposomes in the Therapy of Infections, Diseases, and Cancer. New York: Alan R Liss, 1988: 317–327.

  10. 10.

    Ostro MJ, Cullis PR. Use of liposomes as injectable-drug delivery systems. Am J Hosp Pharm 1989; 46: 1576–87.

  11. 11.

    Sculier J-P, Coune A, Meunier F, Brassinne C, Laduron C, Hollaert C, Collette N, Heymans C, Klastersky J. Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections. Exp J Cancer Clin Oncol 1988; 24: 527–38.

  12. 12.

    Mehta R, Lopez-Berestein G, Hopfer R, Mills K, Juliano RL. Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta 1984; 770: 230–34.

  13. 13.

    Szoka Jr FC, Milholland D, Barza M. Effect of lipid composition and liposome size on toxicity and in viro fungicidal activity of liposome-intercalated amphotericin B. Antimicro Agents Chemther 1987; 31: 421–29.

  14. 14.

    Leserman LD, Machy P, Barbet J. Covalent coupling of monoclonal antibodies and protein A to liposomes: Specific interaction with cells in vitro and in vivo. In Gregoriadis G. (ed.), Liposome Technology, Vol. 3: Targeted Drug Delivery and Biological Interaction. Boca Raton, Florida: CRC Press, 1984: 29–40.

  15. 15.

    Shen D, Huang A, Huang L. An improved method for covalent attachment of antibody to liposomes. Biochim Biophys Acta 1988; 689: 31–37.

  16. 16.

    Hospenthal D, Gretzinger K, Rogers A. Treatment of a murine model of systemic candidiasis with liposomal amphotericin B bearing antibody toCandida albicans. J Med Microbiol 1989; 30: 193–97.

  17. 17.

    Hospenthal DR, Rogers AL, Beneke ES. Effect of attachment of anticandidal antibody to the surface of liposomes encapsulating amphotericin B in the treatment of murine candidiasis. Antimicrob Agents Chemother 1989; 33: 16–18.

  18. 18.

    Dromer F, Barbet J, Bolard J, Charriere J, Yeni P. Improvement of amphotericin B activity during experimental cryptococcosis by incorporating into immunoliposomes. Antimicrob Agents Chemther 1990; 34: 2055–60.

  19. 19.

    McKinney MM, Parkinson A. A simple, non-chromatographic procedure to purify immunoglobulins from serum and ascites fluid. J Immunol Methods 1987; 96: 271–78.

  20. 20.

    Hospenthal DR, Rogers AL, Mills GL. Development of amphotericin B liposomes bearing antibodies specific toCandida albicans. Mycopathologia 1988; 101: 37–45.

  21. 21.

    Belay, T, Hospenthal D, Rogers A, Patterson MJ. Med Vet Mycol.

  22. 22.

    Gehan EA. A generalized Wilcoxon test for comparin arbitrarily single-censored sample. Biometrika 1965; 52: 20–217.

  23. 23.

    Clark MJ, Whitney RR, Olsen SJ, George RJ, Swerdel MR, Kunselman R. Bonner DP. Amphotericin B lipid complex therapy of experimental fungal infections in mice. Antimicrob Agents Chemther 1991; 35: 615–21.

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Correspondence to Alvin L. Rogers.

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Belay, T., Hospenthal, D.R., Rogers, A.L. et al. Treatment of systemic candidiasis in a neutropenic murine model using immunoglobulin G bearing liposomal amphotericin B. Mycopathologia 123, 9–17 (1993). https://doi.org/10.1007/BF01103483

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Key words

  • Free amphotericin B
  • Immunoglobulin G
  • Liposomal amphotericin B
  • Systemic candidiasis