In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice.
The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T. gondii in infected mice. At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads. Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection. Untreated control mice died within 9 days and showed early and predominant lung involvement. All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy. When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy. When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy. All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable. These results indicate that study of the kinetics of parasitic loads in blood and organs may provide additional information on the effect of antimicrobial agents against T. gondii in regard to the evolution of the infection and may represent a reliable basis for the determination of therapeutic regimens in humans.
Piketty
C
C
Institut National de la Santé et de la Recherche Médicale, Unité 13 Hôpital Claude Bernard, Paris, France.
Derouin
F
F
Rouveix
B
B
Pocidalo
J J
JJ
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001921:Brain / Q000469:parasitology; D002981:Clindamycin / Q000627:therapeutic use; D005260:Female; D007700:Kinetics; D008168:Lung / Q000469:parasitology; D051379:Mice; D011739:Pyrimethamine / Q000627:therapeutic use; D013411:Sulfadiazine / Q000627:therapeutic use; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology
D000890:Anti-Infective Agents; D013411:Sulfadiazine; D002981:Clindamycin; D011739:Pyrimethamine