In vitro activity and interaction of clindamycin combined with dihydroartemisinin against Plasmodium falciparum.
Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC(50)) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC(50) and EC(90) levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.
Department of Parasitology, Institute for Tropical Medicine, University of Tuebingen, Germany. ramhartergmx.at
M
M
Ramharter
H
H
Noedl
H
H
Winkler
W
W
Graninger
W H
WH
Wernsdorfer
P G
PG
Kremsner
S
S
Winkler
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002981:Clindamycin / Q000494:pharmacology*; D004338:Drug Combinations; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D002981:Clindamycin; C039060:artenimol