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Antimicrobial Agents and Chemotherapy, February 2003, p. 735-738, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.735-738.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Fosmidomycin, a Novel Chemotherapeutic Agent for Malaria

Bertrand Lell,1,2 Ronnatrai Ruangweerayut,3 Jochen Wiesner,4 Michel Anoumou Missinou,1,2 Andreas Schindler,1,2 Thomas Baranek,4 Martin Hintz,4 David Hutchinson,1 Hassan Jomaa,4 and Peter Gottfried Kremsner1,2*

Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen,1 Jomaa Pharmaka GmbH, Giessen, Germany,4 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,2 Mae Sot General Hospital, Mae Sot, Thailand3

Received 19 July 2002/ Returned for modification 19 August 2002/ Accepted 28 October 2002

In previous studies, fosmidomycin has been shown to possess activity against Plasmodium falciparum in vitro and in the mouse model. It has a novel mode of action through inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme of the nonmevalonate pathway of isoprenoid biosynthesis, which is absent in humans. In this open-label, uncontrolled trial, the efficacy and safety of fosmidomycin, in an oral dose of 1,200 mg every 8 h for 7 days, were evaluated in the treatment of acute uncomplicated Plasmodium falciparum malaria in 20 adult subjects in Gabon and Thailand. Clinical assessments were performed and thick blood smears were evaluated every 8 h until parasite clearance and resolution of symptoms were achieved; assessments continued at weekly intervals thereafter for the duration of the 28-day followup period. All subjects were clinically and parasitologically cured on day 7 (primary end point). Parasite and fever clearance were rapid, with means of 44 and 41 h, respectively. On day 28, seven out of nine subjects (78%) were cured in Gabon and two out of nine subjects (22%) were cured in Thailand. The drug was well tolerated, although mild gastrointestinal side effects were recorded for five subjects. Analysis of hematological and biochemical parameters showed no clinically significant changes throughout the study. Fosmidomycin is an effective and safe antimalarial drug, although its use as a single agent is restricted by the occurrence of recrudescent infections. However, its role in combination therapy should be explored.

* Corresponding author. Mailing address: Institut für Tropenmedizin, Wilhelmstrasse 27, D-72074 Tübingen, Germany. Phone: 0049 7071 29 87179. Fax: 0049 7071 29 5189. E-mail: peter.kremsner{at}uni-tuebingen.de.

Antimicrobial Agents and Chemotherapy, February 2003, p. 735-738, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.735-738.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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