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Antimicrobial Agents and Chemotherapy, August 2006, p. 2713-2718, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.00392-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Fosmidomycin plus Clindamycin for Treatment of Pediatric Patients Aged 1 to 14 Years with Plasmodium falciparum Malaria

Steffen Borrmann,^1,2,3, Ingrid Lundgren,^1,4 Sunny Oyakhirome,¹ Bénido Impouma,¹ Pierre-Blaise Matsiegui,^1,2 Ayola A. Adegnika,^1,2 Saadou Issifou,^1,2 Jürgen F. J. Kun,² David Hutchinson,⁵ Jochen Wiesner,⁶ Hassan Jomaa,⁶ 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 Otto Meyerhof Centre, Heidelberg University School of Medicine, Heidelberg, Germany,³ Mayo Medical School, Mayo Clinic, Rochester, Minnesota,⁴ Jomaa Pharma GmbH, Hamburg, Germany,⁵ Institut für Klinische Chemie und Pathobiochemie, Labor Jomaa, Universitätsklinikum Giessen und Marburg, Marburg, Germany⁶

Received 30 March 2006/ Returned for modification 3 April 2006/ Accepted 25 May 2006

Fosmidomycin plus clindamycin was shown to be efficacious in the treatment of uncomplicated Plasmodium falciparum malaria in a small cohort of pediatric patients aged 7 to 14 years, but more data, including data on younger children with less antiparasitic immunity, are needed to determine the potential value of this new antimalarial combination. We conducted a single-arm study to improve the precision of efficacy estimates for an oral 3-day fixed-ratio combination of fosmidomycin and clindamycin at 30 and 10 mg/kg of body weight, respectively, every 12 hours for the treatment of uncomplicated P. falciparum malaria in 51 pediatric outpatients aged 1 to 14 years. Fosmidomycin plus clindamycin was generally well tolerated, but relatively high rates of treatment-associated neutropenia (8/51 [16%]) and falls of hemoglobin concentrations of 2 g/dl (7/51 [14%]) are of concern. Asexual parasites and fever were cleared within median periods of 42 h and 38 h, respectively. All patients who could be evaluated were parasitologically and clinically cured by day 14 (49/49; 95% confidence interval [CI], 93 to 100%). The per-protocol, PCR-adjusted day 28 cure rate was 89% (42/47; 95% CI, 77 to 96%). Efficacy appeared to be significantly reduced in children aged 1 to 2 years, with a day 28 cure rate of only 62% for this small subgroup (5/8). The inadequate efficacy in children of <3 years highlights the need for continued systematic studies of the current dosing regimen, which should include randomized trial designs.

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

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