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Rifabutin is active in murine models of toxoplasmosis.
Antimicrob Agents Chemother 1994; 38(3):570-5AA

Abstract

Rifabutin, a semisynthetic derivative of rifamycin S, was examined alone and in combination with other drugs for activity in treatment of systemic toxoplasmosis and toxoplasmic encephalitis in murine models. One hundred percent of the mice infected with a lethal inoculum of tachyzoites or cysts of Toxoplasma gondii were protected against death by treatment with doses of 400 or 300 mg of rifabutin per kg administered alone for 10 days. Doses of 200 mg/kg protected at least 80% of the mice, and doses of 100 mg/kg protected 10 to 40% of the infected mice against death. Doses of 50 mg/kg were not protective but caused a delay in time to death. Combination of nonprotective (50-mg/kg) or slightly protective (100-mg/kg) doses of rifabutin with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone that did not confer any protection against death from toxoplasmosis when administered alone resulted in remarkable enhancement of the in vivo activities of all of these drugs. Seventy-five percent of the infected mice survived when treated with 100 mg of rifabutin per kg per day combined with the ineffective dose of 10 mg of pyrimethamine per kg. A dose of 50 mg of rifabutin per kg in combination with the ineffective dosages of clindamycin (25 mg/kg/day), atovoquone (5 mg/kg/day), and sulfadiazine (80 mg per liter of drinking water) protected at least 80, 60, and 60% of the mice against death, respectively. The inflammatory responses in the brains of mice treated for 30 days with 200 mg of rifabutin per kg per day were significantly reduced compared with those in the brains of untreated controls. These observations suggest that clinical trials with rifabutin for treatment and prevention of human toxoplasmosis may be justified, particularly when the drug is used in combination with other drugs with activity against T. gondii.

Authors+Show Affiliations

Research Institute, Palo Alto Medical Foundation, California 94301.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8203856

Citation

Araujo, F G., et al. "Rifabutin Is Active in Murine Models of Toxoplasmosis." Antimicrobial Agents and Chemotherapy, vol. 38, no. 3, 1994, pp. 570-5.
Araujo FG, Slifer T, Remington JS. Rifabutin is active in murine models of toxoplasmosis. Antimicrob Agents Chemother. 1994;38(3):570-5.
Araujo, F. G., Slifer, T., & Remington, J. S. (1994). Rifabutin is active in murine models of toxoplasmosis. Antimicrobial Agents and Chemotherapy, 38(3), pp. 570-5.
Araujo FG, Slifer T, Remington JS. Rifabutin Is Active in Murine Models of Toxoplasmosis. Antimicrob Agents Chemother. 1994;38(3):570-5. PubMed PMID: 8203856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rifabutin is active in murine models of toxoplasmosis. AU - Araujo,F G, AU - Slifer,T, AU - Remington,J S, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 570 EP - 5 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 38 IS - 3 N2 - Rifabutin, a semisynthetic derivative of rifamycin S, was examined alone and in combination with other drugs for activity in treatment of systemic toxoplasmosis and toxoplasmic encephalitis in murine models. One hundred percent of the mice infected with a lethal inoculum of tachyzoites or cysts of Toxoplasma gondii were protected against death by treatment with doses of 400 or 300 mg of rifabutin per kg administered alone for 10 days. Doses of 200 mg/kg protected at least 80% of the mice, and doses of 100 mg/kg protected 10 to 40% of the infected mice against death. Doses of 50 mg/kg were not protective but caused a delay in time to death. Combination of nonprotective (50-mg/kg) or slightly protective (100-mg/kg) doses of rifabutin with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone that did not confer any protection against death from toxoplasmosis when administered alone resulted in remarkable enhancement of the in vivo activities of all of these drugs. Seventy-five percent of the infected mice survived when treated with 100 mg of rifabutin per kg per day combined with the ineffective dose of 10 mg of pyrimethamine per kg. A dose of 50 mg of rifabutin per kg in combination with the ineffective dosages of clindamycin (25 mg/kg/day), atovoquone (5 mg/kg/day), and sulfadiazine (80 mg per liter of drinking water) protected at least 80, 60, and 60% of the mice against death, respectively. The inflammatory responses in the brains of mice treated for 30 days with 200 mg of rifabutin per kg per day were significantly reduced compared with those in the brains of untreated controls. These observations suggest that clinical trials with rifabutin for treatment and prevention of human toxoplasmosis may be justified, particularly when the drug is used in combination with other drugs with activity against T. gondii. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/8203856/Rifabutin_is_active_in_murine_models_of_toxoplasmosis_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=8203856 DB - PRIME DP - Unbound Medicine ER -