Tags

Type your tag names separated by a space and hit enter

In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii.
Antimicrob Agents Chemother 1993; 37(11):2371-8AA

Abstract

The efficacy of atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, and minocycline was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of Toxoplasma growth by an enzyme-linked immunosorbent assay. For in vivo studies, mice were acutely infected intraperitoneally with 10(4) tachyzoites of the virulent RH strain and then treated perorally for 10 days from day 1 postinfection. The following drug regimens were investigated: atovaquone at 100 and 50 mg/kg of body weight per day and the combinations of atovaquone at 50 mg/kg with sulfadiazine at 200 mg/kg, pyrimethamine at 12.5 mg/kg, clarithromycin at 200 mg/kg, or minocycline at 50 mg/kg. Efficacy was assessed by determination of survival rates and sequential determination of parasite burdens in blood, brain, and lungs. In vitro, atovaquone inhibited Toxoplasma growth at a concentration of > or = 0.02 mg/liter; the 50% inhibitory concentration was estimated to be 0.023 mg/liter. No synergistic effect was observed when it was combined with sulfadiazine, clarithromycin, or minocycline, whereas a significant antagonistic effect was noted for the combination of atovaquone with pyrimethamine. In vivo, administration of atovaquone at 100 or 50 mg/kg/day for 10 days resulted in prolonged survival compared with that in untreated mice; this survival was associated with a reduction of parasite burdens in blood and tissues during the course of treatment. The combinations of atovaquone with pyrimethamine, clarithromycin, or sulfadiazine were more efficient than each drug administered alone, in terms of survival, but parasite burdens in blood and organs were not reduced compared with those in mice treated with any of the agents alone. These experimental results confirmed the activity of atovaquone against Toxoplasma gondii, but no marked improvement in efficacy was observed in vitro and in vivo when this drug was combined with pyrimethamine, sulfadiazine, minocycline, or clarithromycin.

Authors+Show Affiliations

Laboratoire de Parasitologie-Mycologie, Hôpital Saint-Louis, Paris, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8285620

Citation

Romand, S, et al. "In Vitro and in Vivo Activities of the Hydroxynaphthoquinone Atovaquone Alone or Combined With Pyrimethamine, Sulfadiazine, Clarithromycin, or Minocycline Against Toxoplasma Gondii." Antimicrobial Agents and Chemotherapy, vol. 37, no. 11, 1993, pp. 2371-8.
Romand S, Pudney M, Derouin F. In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii. Antimicrob Agents Chemother. 1993;37(11):2371-8.
Romand, S., Pudney, M., & Derouin, F. (1993). In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii. Antimicrobial Agents and Chemotherapy, 37(11), pp. 2371-8.
Romand S, Pudney M, Derouin F. In Vitro and in Vivo Activities of the Hydroxynaphthoquinone Atovaquone Alone or Combined With Pyrimethamine, Sulfadiazine, Clarithromycin, or Minocycline Against Toxoplasma Gondii. Antimicrob Agents Chemother. 1993;37(11):2371-8. PubMed PMID: 8285620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii. AU - Romand,S, AU - Pudney,M, AU - Derouin,F, PY - 1993/11/1/pubmed PY - 1993/11/1/medline PY - 1993/11/1/entrez SP - 2371 EP - 8 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 37 IS - 11 N2 - The efficacy of atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, and minocycline was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of Toxoplasma growth by an enzyme-linked immunosorbent assay. For in vivo studies, mice were acutely infected intraperitoneally with 10(4) tachyzoites of the virulent RH strain and then treated perorally for 10 days from day 1 postinfection. The following drug regimens were investigated: atovaquone at 100 and 50 mg/kg of body weight per day and the combinations of atovaquone at 50 mg/kg with sulfadiazine at 200 mg/kg, pyrimethamine at 12.5 mg/kg, clarithromycin at 200 mg/kg, or minocycline at 50 mg/kg. Efficacy was assessed by determination of survival rates and sequential determination of parasite burdens in blood, brain, and lungs. In vitro, atovaquone inhibited Toxoplasma growth at a concentration of > or = 0.02 mg/liter; the 50% inhibitory concentration was estimated to be 0.023 mg/liter. No synergistic effect was observed when it was combined with sulfadiazine, clarithromycin, or minocycline, whereas a significant antagonistic effect was noted for the combination of atovaquone with pyrimethamine. In vivo, administration of atovaquone at 100 or 50 mg/kg/day for 10 days resulted in prolonged survival compared with that in untreated mice; this survival was associated with a reduction of parasite burdens in blood and tissues during the course of treatment. The combinations of atovaquone with pyrimethamine, clarithromycin, or sulfadiazine were more efficient than each drug administered alone, in terms of survival, but parasite burdens in blood and organs were not reduced compared with those in mice treated with any of the agents alone. These experimental results confirmed the activity of atovaquone against Toxoplasma gondii, but no marked improvement in efficacy was observed in vitro and in vivo when this drug was combined with pyrimethamine, sulfadiazine, minocycline, or clarithromycin. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/8285620/In_vitro_and_in_vivo_activities_of_the_hydroxynaphthoquinone_atovaquone_alone_or_combined_with_pyrimethamine_sulfadiazine_clarithromycin_or_minocycline_against_Toxoplasma_gondii_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=8285620 DB - PRIME DP - Unbound Medicine ER -