Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis.
The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.
Dumas
J L
JL
Department of Genetics and Microbiology, Centre Médical Universitaire, Geneva, Switzerland.
Chang
R
R
Mermillod
B
B
Piguet
P F
PF
Comte
R
R
Pechère
J C
JC
D000818:Animals; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000382:microbiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008810:Mice, Inbred C57BL; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000188:drug therapy*
D017963:Azithromycin