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Antimicrobial Agents and Chemotherapy, November 2003, p. 3494-3499, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3494-3499.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vitro Activity and Interaction of Clindamycin Combined with Dihydroartemisinin against Plasmodium falciparum

M. Ramharter,1,2* H. Noedl,3 H. Winkler,4 W. Graninger,4 W. H. Wernsdorfer,3 P. G. Kremsner,1,2 and S. Winkler4

Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Germany,1 Medical Research Unit, Albert Schweitzer Hospital, Gabon,2 Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology,3 Division of Infectious Diseases, Department of Internal Medicine I, University of Vienna, Austria4

Received 23 June 2003/ Returned for modification 30 June 2003/ Accepted 28 July 2003

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 (EC50) 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 EC50 and EC90 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.

* Corresponding author. Mailing address: Institute for Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany. Phone: 49 7071 2982194. Fax: 49 7071 295189. E-mail: ramharter{at}gmx.at.

Antimicrobial Agents and Chemotherapy, November 2003, p. 3494-3499, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3494-3499.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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