Clindamycin Activity Against Chloroquine-Resistant Plasmodium falciparum

Abstract

The clindamycin dose-response curves observed with both chloroquine-resistant and chloroquine-susceptible strains of Plasmodium falciparum in vitro demonstrated a plateau region that extended from 10⁻² to 10¹ µg/ml of drug (22 nM to 22 µM. Similar dose-response curves were also observed with the three major metabolites of clindamycin (clindamycin sulfoxide, de-N-methyl clindarnycin, and de-N-methyl clindamycin sulfoxide). The position of this plateau was time dependent and rose from 20%–25% to 90%–95% inhibition of parasite growth between 24 and 72 hr of exposure to the drug. Clindamycin treatment reduced plasmodial protein and nucleic acid synthesis (as measured by the incorporation of [³H]isoleucine and [³H]hypoxanthine, respectively) but 'did not interfere with knob formation. The combination of quinine plus a fixed concentration of clindamycin (0.1 µg/ml) inhibited growth of the quinine-resistant Indochina I strain, although most of the antiplasmodial activity observed at quinine concentrations M) could be attributed to clindamycin alone.