Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria.

Abstract

Fosmidomycin is effective against malaria, but it needs to be given for > or =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 > or =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/microl and 400 to 749/microl, 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.

• Authors: Steffen Borrmann, Ayola A Adegnika, Félicien Moussavou, Sunny Oyakhirome, Gilbert Esser, Pierre-Blaise Matsiegui, Michael Ramharter, Ingrid Lundgren, Maryvonne Kombila, Saadou Issifou, David Hutchinson, Jochen Wiesner, Hassan Jomaa, Peter G Kremsner
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 9 Pg. 3749-54 (Sep 2005) ISSN: 0066-4804 [Print] United States
• PMID: 16127049 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemisinins
• Drug Combinations
• Sesquiterpenes
• Fosfomycin
• fosmidomycin
• Artesunate

Topics

• Antimalarials (adverse effects, therapeutic use)
• Artemisinins (adverse effects, therapeutic use)
• Artesunate
• Chemistry, Pharmaceutical
• Child
• Cohort Studies
• Dose-Response Relationship, Drug
• Drug Combinations
• Endpoint Determination
• Female
• Fosfomycin (adverse effects, analogs & derivatives, therapeutic use)
• Humans
• Malaria, Falciparum (blood, drug therapy, parasitology)
• Male
• Reverse Transcriptase Polymerase Chain Reaction
• Sesquiterpenes (adverse effects, therapeutic use)