Treatment of disseminated histoplasmosis in hamsters
A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out.
Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g.
All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups.
In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.
Key wordshistoplasmosis hamsters itraconazole treatment antifungical treatment
Unable to display preview. Download preview PDF.
- 1.Ajello L, Chick EW, Furcolow ML. Histoplasmosis. Proc 2nd National Conference. Charles Thomas Publisher. Springfield, Illinois, 1971.Google Scholar
- 2.Alsep S, Dismukes WE. Approaches to the patient with suspected histoplasmosis. In: Remington JS, Swartz MN. Current Clinical Topics in Infectious Diseases pp. 254–256, Mc Graw Hill Book Co. New York, 1986.Google Scholar
- 3.Borelli D. Prevalence of Systemic Mycosis in Latin America. In: International Symposium on Mycosis. Pan Amer Health Org Scient Publ no. 205: pp. 28–38, 1970.Google Scholar
- 4.Cauwenberg G, De Doncker P. The clinical use of itraconazole in superficial and deep mycoses. In: Fromthing RA. International Tele symposium on recent trends in the discovery, development and evaluation of antifungic agents pp. 273–284, JR Prous Science Publisher. Barcelona, 1987.Google Scholar
- 5.George R, Penn R. Histoplasmosis. In: Sarosi G, Davies S. Fungal Diseases of the lung, pp. 69–85, Grune & Stratton Inc. Orlando Florida USA 1986.Google Scholar
- 6.Goodwin RA, Shapiro JL, Thurman GH et al. Disseminated histoplasmosis: clinical and pathologic correlations. Medicine 1980; 59:1–13.Google Scholar
- 7.Goodwin RA, Lloyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine 1981; 60:231–266.Google Scholar
- 8.Iovannitti C, Negroni R, Finquelievich JL, Bava AJ. Histoplasmosis experimental del hamster. Rev Arg Micología. En prensa.Google Scholar
- 9.Negroni R, Robles AM, Arechavala A. Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis. Rev Infect Dis 1980; 2:643–649.Google Scholar
- 10.Negroni R, Robles AM, Arechavala A. Tratamiento de la histoplasmosis con itraconazol. Rev Arg Micología 1986; 9(3):7–11.Google Scholar
- 11.Negroni R, Palmieri O, Koren F, Tiraboschi IN, Galimberti RL. Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans. Rev Infect Dis 1987; 9 (Suppl.1):47–50.Google Scholar
- 12.Negroni R, Palmieri O, Cha Torea JC. Tratamiento de la paracoccidioidomicosis y la histoplasmosis con itraconazol por viá oral. Medicina (Buenos Aires) 1987; 47:505–508.Google Scholar
- 13.Negroni R, Arechavala A, Robles AM. La histoplasmosis diseminada crónica como afección oportunista. Med Cutánea ILA 1987; 15 (6):377–383.Google Scholar
- 14.Pasternak J, Bolivar R. Histoplasmosis in acquired immunodeficiency syndrome (AIDS): diagnosis by bone marrow examination. Arch Intern Med 1983; 143 (10):20–24.Google Scholar
- 15.Rubinstein P, Negroni R. Micosis broncopulmonares del adulto y del niño. 2∘ Edición. Editorial Beta. Buenos Aires. 1981.Google Scholar
- 16.Sarosi G, Davies S. Clinical manifestations and management of histoplasmosis in the compromised patient. In: Warnock DW, Richardson MD. Fungal infections in the compromised patient, pp. 187–198, John Wiley and Sons Ltd. New York, 1982.Google Scholar
- 17.Sathapatayavongs B, Balteger M, Wheat J, Slama T, Wass J. Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks. Medicine 1983; 62:263–270.Google Scholar
- 18.Slama TG. Treatment of disseminated and progressive cavitary histoplasmosis with ketoconazole. Amer J Med 1983; 74:70–73.Google Scholar