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Antimicrobial Agents and Chemotherapy, September 2005, p. 3749-3754, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3749-3754.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Short-Course Regimens of Artesunate-Fosmidomycin in Treatment of Uncomplicated Plasmodium falciparum Malaria

Steffen Borrmann,^1,2, Ayola A. Adegnika,^1,2 Félicien Moussavou,^1,3 Sunny Oyakhirome,¹ Gilbert Esser,^1,2 Pierre-Blaise Matsiegui,^1,2 Michael Ramharter,⁴ Ingrid Lundgren,^1,5 Maryvonne Kombila,³ Saadou Issifou,^1,2 David Hutchinson,⁶ Jochen Wiesner,⁷ Hassan Jomaa,⁷ and Peter G. Kremsner^1,2*

Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,¹ Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany,² Département de Parasitologie-Mycologie, Faculté de Médecine, Université des Sciences de la Santé, Libreville, Gabon,³ Division of Infectious Diseases, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria,⁴ Mayo Medical School, Mayo Clinic, Rochester, Minnesota,⁵ Jomaa Pharma GmbH, Hamburg, Germany,⁶ Institute of Biochemistry, University of Giessen, Giessen, Germany⁷

Received 24 December 2004/ Returned for modification 8 February 2005/ Accepted 30 June 2005

Fosmidomycin is effective against malaria, but it needs to be given for 4 days when used alone. We conducted a study of 50 children with Plasmodium falciparum malaria to evaluate the safety and efficacy of consecutively shortened regimens of artesunate-fosmidomycin (1 to 2 mg/kg of body weight and 30 mg/kg of body weight, respectively; doses given every 12 hours). All dosing regimens were well tolerated. Artesunate-fosmidomycin acted rapidly, resulting in consolidated geometric mean parasite and fever clearance times of 24 h and 15 h, respectively. Treatment regimens of 2 days led to cure ratios of 100% by day 14 (39/39; 95% confidence interval [95% CI], 91% to 100%). Most importantly, the 3-day regimen achieved 100% cure on day 28 (10/10; 95% CI, 69% to 100%). Treatment with artesunate-fosmidomycin was associated with transient grade I or II neutropenia (absolute neutrophil counts of 750 to 1,200/µl and 400 to 749/µl, respectively) in six or two patients, respectively. Artesunate-fosmidomycin demonstrates the feasibility and potential value of short-course artemisinin-based combination chemotherapy with rapidly eliminated combination partners.

Present address: Kenya Medical Research Institute-Wellcome Trust Collaborative Research Programme, Kilifi, Kenya.

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