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Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.

Abstract
It has been demonstrated that fosmidomycin has good tolerability and rapid onset of action, but late recrudescences preclude its use alone; in vitro, clindamycin has been shown to act synergistically with fosmidomycin against Plasmodium falciparum. We conducted a study in pediatric outpatients with P. falciparum malaria in Gabon to evaluate the efficacy and safety of an oral combination of fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively, every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10 patients were treated for 5 days. The duration of treatment was then incrementally shortened in intervals of 1 day if >85% of the patients in a cohort were cured by day 14. All dosing regimens were well tolerated, and no serious adverse events occurred. Asexual parasites and fever rapidly cleared in all patients. Cure ratios of 100% on day 14 were achieved with treatment durations of 5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10 patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients). Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens achieved high efficacy in children with P. falciparum malaria. Fosmidomycin-clindamycin is a promising novel treatment option for malaria.
AuthorsSteffen Borrmann, Saadou Issifou, Gilbert Esser, Ayola A Adegnika, Michael Ramharter, Pierre-Blaise Matsiegui, Sunny Oyakhirome, Dénise P Mawili-Mboumba, Michel A Missinou, Jürgen F J Kun, Hassan Jomaa, Peter G Kremsner
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 190 Issue 9 Pg. 1534-40 (Nov 01 2004) ISSN: 0022-1899 [Print] United States
PMID15478056 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimalarials
  • Fosfomycin
  • Clindamycin
  • fosmidomycin
Topics
  • Administration, Oral
  • Adolescent
  • Animals
  • Antimalarials (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Blood (parasitology)
  • Child
  • Clindamycin (administration & dosage, adverse effects, pharmacology, therapeutic use)
  • Drug Therapy, Combination (therapeutic use)
  • Female
  • Fever
  • Fosfomycin (administration & dosage, adverse effects, analogs & derivatives, pharmacology, therapeutic use)
  • Gabon
  • Humans
  • Malaria, Falciparum (drug therapy, parasitology)
  • Male
  • Parasitemia
  • Plasmodium falciparum (drug effects, isolation & purification)

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