Clindamycin activity against chloroquine-resistant Plasmodium falciparum

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 10(1) micrograms/ml of drug (22 nM to 22 microM). Similar dose-response curves were also observed with the three major metabolites of clindamycin (clindamycin sulfoxide, de-N-methyl clindamycin, 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. Clinidamycin 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 microgram/ml) inhibited growth of the quinine-resistant Indochina I strain, although most of the antiplasmodial activity observed at quinine concentrations less than 50 ng/ml (154 nM) could be attributed to clindamycin alone.