Azithromycin: Antimalarial profile against blood- and sporozoite-induced infections in mice and monkeys

The spectrum of antimalarial activity of thr new macrolide antibiotic azith romycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of Plasmodium yoelii nigeriensis (N-67) in Swiss mice and with simian parasite Plasmodium cynomolgi B in rhesus monkey s. Against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally f rom day 0 to day 3 or from day 2 to day 5 to mice harboring established inf ection. The curative response was also obtained with a 40 mg/kg/day dose ad ministered in an extended seven-dose (days 0-6) regimen. Azithromycin was a lso effective in the causal prophylactic test. since a 50 mg/kg dose from d ay -1 to day +2 protected mice against P. y. nigeriensis (N-67) sporozoite challenge. In comparison, erythromycin did not show either of the above act ivities up to a 405 mg/kg/day dose in identical regimens. Comparison of the ED90 values showed that azithromycin was 31-fold more effective than eryth romycin as a blood schizontocide. In the simian model, trophozoite-induced infections of P. cynomolgi B were cured with 25 mg/kg/day azithromycin admi nistered for 7 days. In the causal prophylactic test, the prepatent period was significantly extended in monkeys challenged with P. cynomolgi B sporoz oites, presumably because of the growth inhibition of preerythrocytic schiz onts in hepatocytes. Azithromycin did not exhibit any hypnozoitocidal (dorm ant exoerythrocytic stages) activity at 15 mg/kg/day in a seven-dose regime n. (C) 2000 Academic Press.